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EPIDEMIC INFANTILE PARALYSIS 
 
 (heine-medin disease) 
 
EPIDEMIC INFANTILE PARALYSIS 
 
 (HEINE-MEDIN DISEASE) 
 
 BY- 
 PROFESSOR PAUL H. ROMER 
 
 Principal of the Institute of Hygiene and Experimental Medicine of Marburg 
 
 Translated by 
 
 H. RIDLEY PRENTICE, M.B., B.S.Lond., M.R.C.P. 
 
 Late Resident Medical Officer to the National Hospital for the Paralysed and 
 
 Epileptic, Queen Square 
 
 With 57 Illustrations in the Text 
 
 NEW YORK 
 
 WILLIAM WOOD AND COMPANY 
 
 MDCCCCXIII 
 

 J-VDG 
 
Translator's Preface. 
 
 It appears highly probable that the disease known as Epidemic 
 Infantile Paralysis will become more and more menacing- to the 
 community in England as well as in other countries. In its sporadic 
 form the disease has been recognized for a long time; its effects on 
 isolated lives have been so deplorable that it has come to be regarded 
 as perhaps the most feared of all the diseases of childhood. But 
 now we are face to face with a change in the way in which the virus 
 attacks the human race ; the disease has become epidemic in its 
 incidence. The history of this remarkable disturbance of the 
 balance between the attack of the virus and the power of effective 
 resistance in human beings is told in the present book. Written as 
 it is by an author who not only has made practical use of the 
 discovery that the disease is communicable to monkeys, but also 
 possesses in a high degree the sense of historical perspective, the 
 book contains the results of his experimental work, and describes 
 fully the difficulties which have stood and still stand in the way of 
 advance in the elucidation of the problems presented by the disease 
 both in its scientific and public health aspects. Under these circum- 
 stances it appears advisable to bring the work within reach of a 
 larger public in this country. 
 
 At the moment of going to press the report on the Swedish 
 epidemic of 191 1 has appeared; it marks a further advance in the 
 study of the disease, and is a brilliant vindication of the claims which 
 Professor Romer has put forward in this book on behalf of the 
 experimental method of investigation. 
 
 London, 1913. 
 
 a 
 
Digitized by the Internet Archive 
 
 in 2010 with funding from 
 
 Open Knowledge Commons 
 
 http://www.archive.org/details/epidemicinfantilOOrm 
 
Pref 
 
 ace. 
 
 The occurrence of cases of epidemic infantile paralysis, the 
 so-called Heine-Medin disease, in Marburg", Hesse-Nassau, gave me 
 the opportunity of making investigations into the etiology of this 
 disease. A considerable portion of these studies has already been 
 published, in the form of short articles, in the Munchener med. 
 Wochenschrift, and in communications to the Medical Society 
 of Marburg. The present work was intended originally not for 
 publication, but merely as an arrangement of the various above- 
 mentioned isolated articles and lectures in a definite and logical 
 form. As the work proceeded, however, the plan became wider, 
 and the book gradually assumed, its present form. The material 
 itself increased in two directions. 
 
 In the first place I soon recognized that the collation of my own 
 humble experimental results alone would give but a feeble repre- 
 sentation of the stage which has been reached in the study of 
 poliomyelitis. Such an experience must fall to the lot of any experi- 
 mental investigator of poliomyelitis who endeavours to give form 
 to his results and, in so doing, makes use of those results alone. 
 This may be easily understood when one considers, that so far the 
 only results which have been of any value in this field of research 
 have depended upon the use of monkeys, and, further, that the cost 
 of procuring and keeping these animals sets very definite limits to 
 the extent of the investigation. Consequently I was obliged to make 
 use of the work of other experimenters, who have attacked the 
 problem with so much success during the last two years, in order 
 to arrive at an even approximate idea of the present state of the 
 question. 
 
 It was pointed out to me by friends that a review of the present 
 state of our knowledge would be of interest to a wider public, and 
 in carrying out this idea I found my material increasing in another 
 direction. The experimental work not only involved necessarily a 
 wide study of the literature, but threw new light on the numerous 
 previous labours undertaken in the investigation of infantile 
 paralysis. I have endeavoured, therefore, to bring before the reader 
 in an orderly manner the mass of scattered material which is to be 
 found in the literature of this and other countries, much of which 
 is accessible only with difficulty. In starting from the idea that a 
 comprehensive representation of the development of our knowledge 
 of Heine-Medin disease up to the present day will be of interest to 
 the reader, I am guided by my own experience. In the summer of 
 
viii PREFACE 
 
 1909, when reports of the epidemic occurrence of poliomyelitis in 
 Germany appeared, I must admit that the disease was relatively but 
 little known to me. It is true that, from the time when I was a 
 student, the classical picture of infantile paralysis, as described in 
 the excellent monograph by Heine, was known to me, and reports 
 of the epidemic occurrence of the disease had reached me from time 
 to time. But, as easily happens when one is not immediately con- 
 cerned with a question, I had not realized that since 1890 our concep- 
 tion of the disease had altered considerably from that contained in 
 most text-books. Consequently, when the epidemic of 1909 once 
 more drew attention to the disease, it was to me more or less of a 
 novelty. I think I do no injustice to my colleagues in the profession 
 if I assume that they also had but a passing acquaintance with the 
 disease, particularly in such districts where it had not assumed 
 epidemic proportions. The following book, therefore, may be 
 perhaps of value; the more so as it seems by no means likely 
 that we are at the end of our experience of this particular pest. 
 The latest reports from Berlin give cause for the fear that further 
 outbreaks are to be expected. 
 
 To the friendly co-operation of Professor Dr. Eduard Muller, 
 the Director of the Medical Polyclinic in this town, whose clinical 
 and epidemiological investigations I was able to follow step by step, 
 and to supplement along experimental lines, I owe the fact that I 
 was enabled quickly to become acquainted with the clinical picture, 
 the epidemiological character and the general significance of the 
 apparently new disease. 
 
 In the following pages I have endeavoured to avoid all that 
 savours of a text-book; they form a resume of my studies. This 
 has been all the easier because, in spite of all the progress which 
 has been made, there are still so many obscure points in the disease, 
 that it is more attractive to discuss the problems which remain than 
 to lose oneself in the description of those already solved. By 
 always drawing attention to the work which remains to be done I 
 hope that I have succeeded in avoiding the tedium which attaches 
 necessarily to a book which is made up largely of references. If I 
 have not succeeded, after all. I ask the reader not to take the will 
 for the deed, but to reckon the will to the deed in my favour. 
 
 In the purely experimental part of this work I have had the 
 pleasure of the extremely intelligent and untiring assistance of 
 Dr. loseph. the present assistant in the bacteriological department 
 of the Hoechst Dve Works. 
 
 P. H. Romer. 
 
 Marburg. 
 
Contents. 
 
 Chapter I. 
 
 The Development of our Knowledge of the Nature of 
 
 the Disease of Heine and Medin. 
 
 Nomenclature, p. i — Historical Retrospect, p. 3. 
 
 Chapter II. 
 The Symptomatology of the Disease in Man. 
 
 PAGE 
 
 I. — Historical 6 
 
 The period before Heine, 6— Heine's work, 7 — From Heine 
 to Medin, 10 — Medin to Wickman, 13. 
 
 II. — The Symptomatology in Man 13 
 
 Period of incubation, 13 — Prodromal symptoms, 13 — Stage of 
 paralysis, 14 (Abortive type, 14; Spinal types, 15; Type 
 simulating Landry's disease, 17; Bulbar and Pontine types, 
 18; Cerebral type, 18; Ataxic type, iq; Polyneuritic type, 
 19; Aleningitic type, 19) — Prognosis, ig — Sporadic infantile 
 paralysis, 20. 
 
 Chapter III. 
 Etiology of the Disease. 
 
 I. — Microscopical and Cultural Researches with Experiments on 
 
 Animals 22 
 
 The older views, 22 — Strumpell's hypothesis, 23 — The era of 
 cocci, 24- — The accumulation of negative results, 25 — Per- 
 sonal bacteriological research, 26 — Important microscopical 
 findings, 27 — Specific intracellular bodies, 29 — " Cultures of 
 the virus,"' 29 — Experiments on animals, 30. 
 
 II. — Experimental Research ox Poliomyelitis in Monkeys — 
 
 Clinical History of Experimental Poliomyelitis 31 
 
 Landsteiner's original experiment, 31 — Personal experiments 
 with monkeys, 32 
 
 [a] Source of the virus used in my experiments ... ... 34 
 
 Susceptibility of monkeys to the virus of poliomyelitis, 42. 
 
 (b) The clinical history of poliomyelitis in monkeys ... ... 43 
 
 Period of incubation, 43 — Prodromal symptoms, 44 — 
 
 Stage of paralysis, 45 ((a) Poliomyelitis acutissima, 46; 
 (b) Poliomyelitis acuta, 47; [c) Typical spinal para- 
 lysis, 47; (d) Bulbar and Cerebral forms, 49; (e) 
 Gastro-intestinal symptoms, 54; (/) Abortive forms, 
 54; (g) Marasmic forms, 56; (h) Recovery from the 
 acute stage, 57; (i) Recovery from the paralysis, S7 ', 
 (k) Relapses, 59) — Prognosis, 60. 
 
X CONTENTS 
 
 PAGE 
 
 III. — The Nature of the Virus ... 61 
 
 Filtration of the virus, 62 — Resistance to glycerine, 63 — The 
 effect of low and high temperatures, 65 — Resistance to 
 drying-, 66 — Behaviour towards disinfectants, 67 — The 
 durability of the virus in animals, 67 — The effect of passing 
 the virus through animals, 68. 
 
 IV. — The Use of other Animals for Experiments 69 
 
 The susceptibility of different animals, 69 — Earlier experi- 
 ments with rabbits, 70 — Krause and Meinicke's experiments 
 with rabbits, 70 — Results of personal experiments, 71 — 
 Results obtained by other observers, 73 — Renewed repetition 
 of the experiments, 75 — Criticism of the arguments in favour 
 of using rabbits, 77 — Further objections to experiments with 
 rabbits, 82 —An attempt to explain the difference, 8^? — - 
 Practical conclusions, 84. 
 
 Chapter IV. 
 
 Pathology and Pathogenesis. 
 
 I. — Historical Retrospect — The Salient Features 87 
 
 Heine's views, 87 — From Heine to Charcot, Roger and 
 Damaschinn, 89 — The dispute over Charcot's theory, 91 — 
 Investigation of chronic cases, 91 — Investigation of acute 
 cases, 92 — Wickman's investigations, 93 — More recent inves- 
 tigators, 94. 
 
 II. — The Distribution and Spread of the Virus within the 
 
 Organism 94 
 
 The demonstration of the virus in different organs, 94 ; in 
 man, 95 ; in monkeys, 95 — Conclusions, 98 — The methods of , 
 inoculation, gg — Attempts to determine the point of entrance 
 of the virus, 101. 
 
 III. — The Pathological Changes found in Experimental Polio- 
 myelitis in Monkeys compared with those found in Man 102 
 Technique, 103 — Macroscopic changes, 103 — Microscopic 
 changes, 106 (Pia, 107; Spinal cord, 111; Medulla and pons, 
 120; Brain, 122) — The stage of repair, 125 — The final 
 stage, 127 — Poliomyelitis in adults, Landry's paralysis, 
 polyneuritis, rabies and Borna's disease in their relation to 
 Heine-Medin disease, 128. 
 
 IV. — Pathogenesis ' ; 129 
 
 The point of attack of the virus, 129 — The spread of the virus 
 within the central nervous system, 132 — The route by- .which 
 the virus reaches the spinal cord, 133 — The portal of entry 
 of the virus, 134 — Conclusions, 135. 
 
 Chapter V. 
 Epidemiology.' 
 
 I. — History of the Epidemics 136 
 
 Early reports, 136 — The epidemics in the different countries 
 (Sweden and Norway, 136; Germany, 138; Austria, 138; 
 Holland and Switzerland, 139; England, 139; France, 139; 
 Spain, 140; Italy, 140; Russia, 140; North America, 140; 
 Cuba, 141 ; Australia, 141) — The origin of the large 
 epidemics, 141. 
 
CONTENTS xi 
 
 PAGE 
 
 II. — The Epidemiological Characteristics of the several Outbreaks 142 
 Season, 142 — Age, sex, predisposition, 142 — Proof of con- 
 tagiousness, 144 — Confirmation of Wickman's statements, 146. 
 
 Chapter VI. 
 
 The Fight against the Disease. 
 
 ].— Immunity and Immunization 149, 
 
 Clinical and epidemiological experience, 148 — Attempts to 
 reinfect monkeys, 151 — Methods of immunization in monkeys, 
 156; a) Protective inoculation with dry virus, 156; 
 (0) Immunization by small doses of virulent material, 157; 
 (7) Immunization with virus attenuated or killed by chemi- 
 cal means, 158; (8) Immunization with heated virus, 159; 
 (e) Immunization with mixtures of virus and serum con- 
 taining antibodies, 160; (0 Immunization during the incuba- 
 tion period, 162; (y) The biological connection between 
 poliomyelitis and rabies from the point of view of immunity, 
 162. 
 
 II. — Specific Antibodies 162 
 
 Fixation of complement, 162 — Specific hypersensitiveness, 163 
 — Successful demonstration of antibodies, 163 — Serum dia- 
 gnosis, 166 — Serum therapy, 171. 
 
 III. — Experiments with Drugs .. -173 
 
 IV. — Prophylaxis ... 174 
 
 Private prophylaxis, 175 — State regulation, 177. 
 
 Conclusion 178 
 
 Literature 180 
 
 Index igo, 
 
CHAPTER I, 
 
 The Development of our Knowledge of the 
 Nature of the Disease of Heine and Medin. 
 
 -Jakob v. Heine, who gave the first classical 
 description of the disease, gave it the name, " Spinal Infantile 
 Paralysis." He adopted this nomenclature because the cases which 
 came under his observation were either children or adults who had 
 been stricken with the disease during childhood; further, by a process 
 of deductive reasoning carried out with great analytical clearness, 
 he was convinced that the site of the lesion must be in the spinal 
 cord. That this denomination was in general accurate is proved by 
 the manner in which this name of the disease, which he was the 
 first to differentiate as a clinical entity, has been preserved even to 
 the present day. An attempt was made by the French writers to 
 give currency to the terms "idiopathic" or "essential" infantile 
 paralysis; but even at a time when the site of the lesion was not 
 definitely proved these terms betrayed themselves as mere confes- 
 sions of ignorance, and they rightly disappeared entirely when the 
 spinal origin of the disease was clearly demonstrated. 
 
 When knowledge of the anatomical distribution of the funda- 
 mental pathological process advanced, a more exact anatomical term 
 was added to the former appellation, in accordance with the 
 tendency towards an anatomical nomenclature of diseases in general, 
 and the name " Poliomyelitis Anterior Acuta " was coined, which 
 expressed the favourite point of attack of the disease. 
 
 In the middle of the 'eighties observations on groups of cases, 
 in a few instances of epidemics, of the disease began to accumulate, 
 and in accordance with the newly gained knowledge the names 
 "Epidemic Infantile Paralysis" and " Epidemic Poliomyelitis" came 
 into use. But when Medin proved that the hypothesis of Strumpell 
 and Pierre Marie was correct, that there was a connection between 
 classical infantile paralysis and certain forms of encephalitis, these 
 names were no longer satisfactory. According to these authors the 
 same pathological agent may produce at one time, by affecting the 
 spinal cord, the well-known disease described in a masterly manner 
 by v. Heine, at another time, by affecting the brain, a cerebral 
 paralysis. 
 
 I 
 
2 EPIDEMIC INFANTILE PARALYSIS 
 
 In spite of these facts, however, the old term " Spinal Infantile 
 Paralysis " held its ground, even though it was demonstrated that 
 not infrequently adults were attacked by the disease. The name 
 " Paralysie infantile," introduced by the French authors, hereby also 
 lost all justification. 
 
 There were three reasons why the name " Spinal Infantile 
 Paralysis " remained without a rival, besides the obvious historical 
 one, vis., the authority of v. Heine. In the first place it was 
 doubted whether a disease which presented so constant and so 
 definite a clinical picture as spinal paralysis could have a pathological 
 cause identical with a disease showing such a remarkable difference 
 from the clinical point of view as cerebral paralysis. Secondly, it 
 was difficult to believe that a disease, which appeared to be a 
 definite system disease of the spinal cord, could fall out of its role 
 so far as to be bound to no system. Pathological investigation, 
 which took place usually in cases of long standing (owing to the 
 fact that fatal acute cases were inaccurately diagnosed), showed 
 that the site of the lesion corresponded with the clinical picture and 
 involved practically exclusively the grey matter of the anterior 
 horns. Finally, the absence of any new, accurate, comprehensive, 
 and simple term led to the retention of the old, even though it 
 was recognized to be unsatisfactory. 
 
 In the meanwhile our knowledge of the histology of the disease 
 had increased and changed; investigation of recent cases had shown 
 that lesions were to be found in the medulla, pons, and cerebrum, 
 as had been expected by the more acute clinicians. To call the 
 disease a " myelitis " was unsatisfactory, and the term was applicable 
 to only a fraction of the cases. After Rissler, Wickman, v. Harbitz 
 and Scheel had proved that the disease did not limit itself to the 
 grey matter, but usually involved the meninges and frequently the 
 white matter of the cord and brain, the term " poliomyelitis " was 
 clearly too narrow. These results having been confirmed on all 
 hands, an attempt was made to give expression to the anatomical 
 knowledge thus gained; the name " Meningo-myelo-encephalitis 
 disseminata " was evolved. Besides the fact that such a name could 
 not meet with general use, it was by no means free from objections. 
 
 It is to the credit of Wickman, whose work we shall discuss 
 more fully later, that he drew attention to cases which were un- 
 doubtedly caused by the same virus as the cases of epidemic infantile 
 paralysis, and yet showed no definite signs of paralysis. Clearly it 
 would be ridiculous to call such cases paralysis; the term polio- 
 myelitis might still be applicable to these abortive cases, because 
 it appears likely that some degree o'f inflammation of the grey 
 matter was present; yet anatomically this has not been clearly 
 proved. Wickman found a way out of these manifold difficulties. 
 He proposed the name " Heine-Medin " for this disease, which 
 was so kaleidoscopic in its symptomatology, so variable from the 
 point of view of pathological evidence, and the etiology of which 
 was so entirely unknown at that time. 
 
OUR KNOWLEDGE OF THE NATURE OF THE DISEASE 3 
 
 No one can object to the association of the names of these 
 two men with the disease. Heine gave the first classical description 
 of the disease, and Medin was the first to correlate the various types 
 and provide us with a comprehensive view of the disease. It is 
 true that such a name is unsatisfactory because, where possible, 
 the name should express the essential character of any disease; but 
 in the present instance our knowledge is insufficient to enable us 
 to do this. We have seen what difficulties and perplexities stand 
 in the way of any anatomical nomenclature, and it must be admitted 
 that our knowledge of the question of etiology is still in its infancy. 
 The wider the term now chosen, the less will be the likelihood 
 that future researches will necessitate further change. On the 
 other hand, there is no fear that the name " Heine-Medin " is so 
 wide and indeterminate that diseases not belonging to this class 
 will be included under it. By means of experiments with apes 
 we are in possession of an infallible criterion to decide whether a 
 particular doubtful case should or should not be classified as one 
 of Heine-Medin disease. We therefore agree with Wickman and 
 in future shall call all cases belonging to the group which he has 
 established so brilliantly, both from its clinical as well as from its 
 epidemiological aspect, cases of Heine-Medin disease. There are 
 further practical advantages. During the epidemic, in answer to 
 my question as to whether any connection could be traced between 
 a particular case of infantile paralysis and previous cases, doctors 
 have frequently replied in the negative because they have known 
 of no cases of paralysis. If the name " Heine-Medin " be adopted, 
 it is to be hoped that the discovery of Wickman will become more 
 widely known, namely, that although paralysis is the outstanding 
 feature of the disease it is very possibly by no means the most 
 common feature. 
 
 The nomenclature proposed by Wickman will be used in this 
 book; at the same time, for practical reasons, the exciting cause 
 of Heine-Medin disease will be referred to as " Poliomyelitis Virus " 
 (abbreviated: p.m. virus). This term expresses one of the most 
 important characteristics of the virus, which has not been isolated 
 as yet, namely, its tendency to attack the grey matter of the spinal 
 cord. We do not scruple to speak of the virus and bacillus A 
 tuberculosis, even though we know that on occasion Koch's bacillus 
 does not form tubercles. 
 
 Historical Retrospect. — As in most directions in medicine, we 
 owe our knowledge of the disease of Heine and Medin to a few 
 exceptional men. The extent of our indebtedness to them will be 
 particularized in the chapters which deal separately with the clinical 
 aspect, the etiology, the epidemiology, and the pathogenesis of the 
 disease. Others have done much in a small way to fill the gaps 
 left by the men of wide views and imagination, but as time pro- 
 gresses their work will become more and more of an anonymous 
 character. 
 
 At the beginning of the history of the disease one name stands 
 
4 EPIDEMIC INFANTILE PARALYSIS 
 
 out, that of Jakob v. Heine. It is to his credit that he isolated a 
 type of flaccid atrophic paralysis from the chaos of the multitudinous 
 forms of paralysis affecting children. He chose the name " Spinal 
 Infantile Paralysis " because of the supposed site of the lesion. 
 His excellent description remained for years the basis of all the 
 accounts of the disease in the text-books, and for a long time, with 
 the exception of the discovery of the changes in the electrical 
 reactions by Duchenne and Erb, no important addition was made 
 to it by other observers. It was not until the occurrence of the 
 great Swedish epidemics that Medin and Wickman discovered that 
 the disease " Spinal Infantile Paralysis " was only the common 
 symptom-complex produced by a disease which more rarely 
 appeared in a bulbar, cerebral, polyneuritic, ataxic, meningitic or 
 abortive form, or as Landry's paralysis. Owing to the length of 
 time which had elapsed, during which the disease had been con- 
 sidered as a fully described entity, the many-sided picture of the 
 disease drawn by the Swedish authors was surprising and noveL 
 Many considered that the disease so described had nothing to do 
 with Heine's disease, while others fell back upon the hypothesis 
 that the disease had changed in the manner of its manifestation. 
 As a matter of fact, the only change which had taken place was 
 in the extent of our knowledge. It is necessary to recognize this- 
 important fact in estimating the value of the contributions of the 
 Swedish investigators. Their results have been confirmed by all 
 the painstaking work which has been done in the more frequent 
 epidemics of later years. 
 
 Pathological and anatomical investigations have advanced pari 
 passu with the clinical, in this as in other departments of medicine. 
 Heine placed the lesion in the spinal cord on theoretical grounds; 
 the proof of the existence of an organic lesion was furnished later 
 by microscopical investigation at the hands particularly of French 
 authors (Prevost and Vulpian, Charcot and Joffroy, Roger and 
 Damaschino). who called attention to the most important change of 
 all, the atrophy of the ganglion cells. The French authors also 
 pointed out the importance of the interstitial changes which occurred 
 in the cord. Subsequently, pathological discussion raged round the 
 question whether the parts primarily affected were the ganglion 
 cells, as maintained by Charcot, or the supporting structures of 
 the cord. It cannot be said even at the present day that this 
 question has been decided finally one way or another. But the 
 researches of Rissler in acute cases have enabled us to say definitely 
 that the disease consists in a disseminated, infiltrative, inflamma- 
 tory process, which may attack any portion of the central nervous 
 system, but which shows a predilection for the spinal grey matter. 
 Wickman particularly not only confirmed and extended our know- 
 ledge of the actual, demonstrable, pathological changes, but threw 
 new light upon the question of the pathogenesis of the disease. 
 Recent experiments with animals appear to be leading to a still 
 more clear conception of the pathology and pathogenesis of Heine- 
 Medin disease. 
 
OUR KNOWLEDGE OF THE NATURE OF THE DISEASE 5 
 
 The history of the epidemiology is of more recent date; in 
 the 'eighties endemic occurrence of the disease was noted, epidemics 
 were observed only at the beginning of the 'nineties. The first 
 ■epidemics served only to increase clinical knowledge of the disease. 
 Wickman 's thorough work on the epidemiology dates from 1907; 
 he produced proof that the disease is contagious and his conclusions 
 have been borne out in the main by subsequent investigators. 
 Successful investigation of the etiology is of very recent date. 
 Since Strumpell first came to the conclusion that the disease was 
 due to an exogenous, living agent, and as a result of the con- 
 firmation of his views by subsequent epidemics, the etiological 
 aspect has had similar justification and importance as the other 
 .aspects of the disease. After passing through several phases this 
 work has now entered on a new path owing to the success of 
 Landsteiner in transmitting" the disease to apes. At present we 
 are at the beginning of this line of research, but already important 
 additions to our knowledge of the active agent have been made, 
 the pathology and pathogenesis becoming better known thereby, 
 while at the same time a further stage in the understanding of the 
 ■epidemiology has been reached; finally, there is now some hope 
 in the direction of actual combating of the disease, either by means 
 of hygienic measures or of drugs. 
 
 This short resume of the history of the disease of Heine and 
 Medin bears out what I said at the beginning, that it resolves 
 itself into a series of steps made by a few remarkable men. The 
 clinical aspect is bound up with the names of Heine, Medin, and 
 Wickman; pathological research from the purely descriptive point 
 of view begins with Charcot's teaching that the ganglion cells are 
 the elements primarily affected, and the critical histological studies 
 of Wickman have been the most important subsequent additions 
 to our knowledge in this field. Wickman must be regarded as the 
 founder of the epidemiology, while Strumpell laid the foundations 
 of the etiology of the disease by his brilliant hypothesis and 
 Landsteiner has led the way in the elucidation of the etiology by 
 means of his experiments on animals. 
 
CHAPTER II. 
 
 The Symptomatology of the Disease in Man. 
 
 I.— HISTORICAL. 
 
 The Period before Heine. — It was not possible that such a 
 disease could have been overlooked by the medical profession before 
 Heine's time. The credit of having described cases is generally 
 given to the Englishman, Underwood, who flourished about the 
 middle of the eighteenth century. According to Seeligmuller's 
 critical analysis of the report it appears that it was inaccurate and 
 did not differentiate between the paralysis due to spinal infantile 
 palsy and that due to other spinal lesions, e.g., vertebral caries. 
 The German, Jorg (1816), wrote the first description to which 
 exception cannot be taken. His description is as follows: — 
 
 The little girl was born healthy, although the mother was by no 
 means strong. When a few weeks old the child suffered from some violent 
 fever, of the nature of which the parents could tell me nothing, but which 
 seemed to have been caused by a chill and to be of the nature of those 
 typhoid fevers to which children are so subject and which make such 
 devastating inroads on their whole economy. The illness lasted a long 
 time, and the parents and the doctor despaired of all hope. In spite of 
 this the child gradually recovered from the fever, although she remained for 
 a long time wasted and weak. About the same time the mother suffered 
 from some illness of which she very nearly died and the child consequently 
 was left to the care of strangers. When the mother had recovered suffi- 
 ciently to resume the care of the child she noticed that it did not move 
 its feet properly ; it became more and more clear that the feet were becoming 
 clubbed. 
 
 Heine, who referred to this case of Jorg, also called attention 
 to an observation of Briick (1839), who mentions the case of a boy 
 who developed contractures of all limbs after infantile paralysis. 
 The case reported by Badham (1836), quoted in full by Heine, 
 probably does not belong to this group; indeed, the author himself 
 regarded the paralysis as of cerebral origin. The communications 
 of Badham, however, are of importance inasmuch as they were 
 the cause of the first publications of Heine. Badham wrote " What 
 is the cause of this paralysis ? Of what nature is it ? What is to 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAN 7 
 
 be done against it ? The author would be glad to know the 
 answers to these questions and he calls upon the medical men of 
 all nations to publish their experiences and views in this important 
 matter.'' In too modest a fashion Heine prays that his publication 
 '' may not be taken to be an answer to the questions put before 
 the medical world by the English doctor." As a matter of fact, 
 however, Heine's first monograph contains as complete an answer 
 to these questions as was possible, considering the standpoint of 
 medicine at that time and the amount of material which was at 
 his disposal. 
 
 Heine's Work. — The method of Heine throws much light on 
 the methods involved in all successful investigations. It follows 
 in the main a procedure opposite to that used by Medin, which 
 we shall consider later. Heine collected cases of a definite type 
 out of the numerous records of paralysis in children, and raised 
 this type, the flaccid atrophic spinal type, into a definite clinical 
 entity. We know now that the cases selected by Heine did not 
 exhaust his material from the etiological point of view, and that 
 consequently his classification was too narrow. This does not 
 detract from the value of Heine's services, which lay in the 
 differentiation of a type from amongst the medley of inco-ordinated 
 observations of which his material was composed. He had suc- 
 ceeded in discovering the most common form of the disease and 
 his work is a standing example of the value of applying an arbitrary 
 principle in a schematic and orderly way to a mass of clinical 
 observations; the result may not give a complete explanation of 
 all the appearances, but it undoubtedly leads to a widening of our 
 conception of the disease and to an actual increase of knowledge. 
 
 In the text-books and in many modern monographs Heine is 
 given credit for being the classical observer of the symptomatology 
 of the chronic stage of infantile paralysis. But it must not be 
 forgotten that he was well aware of the acute stage ; he writes : 
 " Two stages can be made out at once, a primary acute stage 
 and a secondary chronic one ; the two stages merge into one 
 another without any definite dividing line." He gives the following 
 description of the acute stage : — 
 
 The disease attacks children who are healthy and well developed at 
 the age of from 6 to 36 months. Usually they have suffered from no illness 
 previously, in some cases they have been somewhat unwell for a short time. 
 The incidence is sudden, occurring with fever, congestion of the head, rest- 
 lessness, and, in short, symptoms of general irritation. At the same time 
 there are signs of difficulties in dentition, the children put their hands to 
 their mouths, from which saliva pours, the gums are swollen in places and 
 are hot, sleep is restless, broken by paroxysmal cries, and the eyelids are only 
 half closed. Sometimes the disease begins with vomiting, diarrhoea, or the 
 appearances of acute rheumatism. Rarely one of the exanthemata seems 
 to be at the root of the matter. Subsequently there may be more or less 
 severe convulsions, which may recur. In two children, whom I treated 
 later, the illness began suddenly with convulsions, collapse, frothing at the 
 mouth and nose, and lividity. In other cases the paralysis appears after 
 
8 EPIDEMIC INFANTILE PARALYSIS 
 
 only slight general symptoms of fever which may be overlooked ; the child 
 goes to bed apparently healthy and is found paralysed in the morning. 
 This mild type of onset is the more common form and often leads both the 
 doctor and the parents to take too hopeful a view of the illness. The danger 
 to life in such cases is very slight, but there is no doubt that in the more 
 violent cases the child is in considerable danger, although no directly fatal 
 case has come to my knowledge. The convulsions are limited to a single 
 attack in most cases, but rarely the initial attack is followed by several 
 minor paroxysms. After the convulsions the child lies quiet, pale and 
 exhausted, looking about the room as if just awakened from a sleep — [in the 
 First Edition Heine writes " paralysis suspendit convulsiones "] and it 
 appears to the parents as if convalescence will be rapid until they find on lift- 
 ing the child that it is paralysed. The lower extremities are most frequently 
 affected ; often in conjunction with the muscles of the trunk, so that the 
 patient not only loses the power of walking, but even of sitting up and 
 of holding up the head. Frequently one leg is affected, but without the 
 corresponding arm, as in the hemiplegic type of the disease ; a few separate 
 muscles may be affected in each leg. In the rarest cases one arm and 
 shoulder being affected the limb hangs by the side, while the lower 
 extremities remain quite untouched. The bladder and rectum are some- 
 times weakened for a time, but never permanently affected. With the 
 occurrence of paralysis the first stage of the disease is finished and it passes 
 into its second stage. 
 
 This description, in my opinion, is still worth recalling in 
 the light of our subsequent knowledge. It is true that Heine 
 depicts the acute stage mainly from facts obtained from the history 
 of the cases, but this scarcely diminishes the value of his state- 
 ment, as the obtaining" of a good history is one of the most 
 important parts of clinical examination and is an art in itself which 
 is by no means understood by everybody. Eduard Miiller has 
 lately called attention to the great importance of a good history 
 in just these cases; further, the doctor rarely has an opportunity 
 of observing the acute stage of the disease, except during an 
 epidemic. Even as late as the year 1878, we find Seeligmuller com- 
 plaining that there was but one description of the acute stage in 
 the literature, that written by Dr. Ehrenhaus, an assistant of Dr. 
 Henoch. 
 
 Heine may be considered the founder of the symptomatology 
 of both the acute and chronic stages of the disease. Following 
 on a short communication to the Society for the Study of Natural 
 History at Freiburg, in 1838, his first monograph appeared in 
 1840. In this he describes fourteen cases of paraplegia, seven cases 
 of " hemiplegia," which term he uses to connote paralysis of one 
 extremity, i.e., cases which we should -call monoplegia, and six 
 cases of partial paralysis. In the same monograph he describes 
 four cases of paralysis due to cerebral lesion, which he differentiates 
 sharply from the rest by laying stress on the spastic nature of the 
 paralysis ; he thus lays the foundation of his classification of the 
 paralyses according to their spastic or non-spastic character, which 
 classification has been adhered to down to the present day. The 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAX CJ 
 
 correctness and comparative completeness of his description is 
 generally admitted; in particular he called attention to the absence 
 of sensory disturbance and to the fact of recovery taking" place 
 from even extensive paralysis. He says also : :< The gradual 
 reduction of the paralysis, both in extent and in intensity, gives 
 ground for the belief that it is due to the gradual re-absorption 
 of exudate around the nervous elements, - whereby the latter are 
 partially relieved from pressure." This shows that he had some 
 idea of the nature of the pathological process involved. He 
 recognized that the mental condition of his patients was good 
 (" some of them showed much talent "), and he describes with 
 great clearness the paralysis, the atrophy, the contractures, the 
 delayed growth of bone and the other deformities. From the point 
 of view of etiology, he believes that delayed and difficult dentition 
 is to be blamed. Finally, he showed the way towards the correct 
 orthopaedic treatment of the permanently paralysed. 
 
 It is surely of value to save from oblivion the life-history of so remark- 
 able a man. Bv the courtesy of Dr. Sick, the Director of the Municipal 
 Hospital of Stuttgart, I am in possession of the Proceedings of the Wiirlem- 
 berg Medical Society; in vol. 1, 188.0, there are to be found the following 
 biographical notes : — ■ 
 
 " Jakob Heine was born April 16, 1800, at Lauterbach, a village 
 in the Black Forest. His father kept an inn, and was also a farmer. 
 At first he attended the village school, but he soon showed desire 
 for a wider education. When aged 13 he tried to enter the Gymnasium at 
 Rottweil, but was not accepted as he was already too old. For some time 
 he followed his father's occupation. The desire for a scientific training 
 left him no peace, and at the age of 21 he entered the classical school 
 at Altirsbach, where he worked side by side with boys from 8 to 14 years 
 old. In the autumn of 1822 he entered the Gymnasium at Rottweil, and in 
 a short time, by untiring effort, he passed his examination. In 1S23 he 
 entered the University of AVtirzburg, where the influence of his uncle Heine, 
 ' the Father of Orthopaedics,-' soon caused him to give up theology for 
 medicine. He carried on his studies with great assiduity and under many 
 difficulties. He acted for a time as assistant to Schonlein, and in the 
 surgical clinic of Textor ; he was also prosector of anatomy. He graduated 
 in AVtirzburg, and passed the AViirtemberg State Examination at Tubingen 
 in 1S29. Shortly afterwards he was asked to arrange a State orthopaedic 
 hospital. He chose the town of Cannstadt, where he opened the institution 
 in 1829. As so often happens when a new special hospital is founded, the 
 patients who appeared wanting orthopaedic treatment seemed literally to 
 spring out of the ground, and enlargement of the hospital speedily became 
 necessary. Heine married Henriette Camerer, daughter of the Director of 
 the Catholic Council in Stuttgart, in 1831. Patients of all countries and 
 of all ranks came in great numbers to his institution. 
 
 " Apart from the two monographs which appeared in 1840 and i860 
 Heine did not write anything. 
 
 " He received many personal honours. In 1830, as a result of the 
 immediate success of his institution, he was given the freedom of the town 
 of Cannstadt and the title Hofrat. Later he obtained the title Geheimer 
 Hofrat, and was the recipient of many Orders. He retired into private life 
 
IO EPIDEMIC INFANTILE PARALYSIS 
 
 in 1S65. He had the proud pleasure of seeing one of his sons become 
 surgeon and lecturer at the University of Prague, although he had the 
 sorrow of seeing this same son die before him in 1S77. Heine died 
 November 12, 1879, in Cannstadt. His life was that of a man of manly 
 character who rejoiced in overcoming obstacles; he is said to have 'had 
 good luck,' but, as a matter of fact, his success was due to his magnificent 
 energy and self-confidence. " ; 
 
 The best clinicians, Romberg, Bardeleben, Duchenne, and 
 Rilliet praised his work. Rilliet and Barthez, who wrote on 
 infantile spinal paralysis in 1843, did not know of his work at that 
 time and used the term '* essential infantile paralysis " because 
 they were unable to find any changes in the spinal cord post 
 mortem. In a later work (.1851) they recognized the importance 
 of Heine's work, but again rejected the term "spinal," owing to 
 their repeated negative results at autopsies. 
 
 In England attention was turned to the paralyses of children. 
 In 1850, Kennedy described cases of "temporary paralysis" in 
 which, however, there is some doubt as to whether they were due 
 to the same cause as Heine's cases. The English physician, West, 
 coined the term "paralysis of the morning" in 1852; this term 
 was used for a long time, although, judged by the standard of our 
 present knowledge, it has little to recommend it. In i860, Heine's 
 second monograph appeared; in it he gives records of 150 further 
 cases, and localizes the lesion in the spinal cord with certainty by 
 purely deductive reasoning. We shall return to this point later. 
 
 From Heine to Medin. — The next thirty years did not add 
 much to the clinical knowledge of the disease. Of importance was 
 the demonstration of the change in the faradic reactions of the 
 muscles by Duchenne, and his conclusion from this that the disease 
 was spinal in its localization. He invented the name " Paralysie 
 atrophique graisseuse de l'enfance," which was but little used. 
 Erb followed with observations on the changes in the galvanic 
 reactions and formulated his theory of the " reaction of degenera- 
 tion." Otherwise, as far as progress in the field of clinical in- 
 vestigation was concerned, the period produced nothing. The 
 text-books of the time followed Heine's description, with the 
 addition of the results of investigations of Duchenne and Erb. 
 Many isolated observations were put on record during the years 
 i860 to 1890, which tended more and more to show that the 
 description given by Heine was becoming too narrow and that 
 the conception of the disease needed broadening'. However, 
 nothing definite was achieved, firstly, because the several observa- 
 tions remained isolated, and. secondly, because at that time men's 
 energies were directed mainly in the direction of topographical 
 diagnosis. The man with true scientific insight had not arrived. 
 
 Among these observations, which showed that the limit drawn 
 by Heine was too narrow, were some which proved that the disease 
 might attack adults. Such were those of Meyer (i860), Duchenne 
 fils (1864), and particularly the elder Duchenne, Erb and Charcot, 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAN II 
 
 who based their conclusions on positive anatomical evidence. 
 Others were Schultze, 1878;' Friedlander, 1882; Leri and Wilson, 
 Rissler, 1888; Leegaard, 1889; Williamson, v. Kahlden, Middleton, 
 Jagic, Roder and Bickel, Sherman and Spiller, Taylor, van 
 Gehuchten. 
 
 Some observers pointed out the similarity or even the identity 
 of the pathological processes in infantile paralysis and Landry's 
 disease. These were Petit fils, Zimmermann, who in 1885 examined 
 a case of Landry's paralysis and came to the conclusion that this 
 disease and infantile paralysis formed only different degrees of one 
 and the same disease; Buss in 1887, and particularly Raymond. 
 
 In other directions also the accepted idea of the disease began 
 to fall in pieces. Erb recognized that there are cases of paralysis 
 which are identical with infantile paralysis and which end in com- 
 plete recovery; Duchenne in 1855, Volkmann in 1870, and Frey 
 in 1874, had already described similar cases. The similarity be- 
 tween certain forms of paralysis due to medullary and pontine 
 lesions and anterior poliomyelitis was put on record. Eisenlohr, 
 in 1880, described some typical cases. But it was Oppenheim who 
 in 1883 formulated clearly an " encephalitis pontinea," which was 
 in close relationship to infantile paralysis. Thus we see how the 
 original conception of the disease gradually became widened; but, 
 owing to the absence of any criterion by which the several varieties 
 could be judged and included or excluded in the general group, 
 no definite restatement of the position was possible. 
 
 The most important advance was made by Strumpell; he placed 
 certain cerebral palsies in the same group with the spinal infantile 
 palsies. The importance of this step lies in the appearance of a 
 new etiological standpoint, by which Strumpell justified his classifi- 
 cation, and which was accepted later by Jendrassik and Fierre 
 Marie. Strumpell also connected etiologically certain forms of 
 neuritis with poliomyelitis. I have no doubt that if Strumpell 
 had had the opportunity of observing an epidemic he would have 
 antedated the discoveries made by Medin. His arguments seem to 
 me to be of such importance as to merit quotation. In 1884 he 
 wrote : — 
 
 Even the general course of these diseases shows great similarity. 
 Multiple neuritis and poliomyelitis appear in similar varieties ; they show 
 the same gradation between the acute and the chronic forms. Both affect 
 principally the motor tracts, although owing to the peripheral nerves being 
 affected in the one and the spinal cord in the other there are many minor 
 differences in the symptoms. It follows that the purely anatomical classi- 
 fication between neuritis, poliomyelitis, and acute encephalitis, which is 
 now in vogue must be looked upon as an artificial one. It seems to us 
 worth while to consider whether all these diseases may not be brought under 
 one etiological heading, and whether they may not be considered to be 
 different local manifestations of the same disease, or at least of very closely 
 allied diseases. In this connection one might apply the analogy between 
 croup and faucial diphtheria to the diseases, multiple neuritis and 
 
12 EPIDEMIC INFANTILE PARALYSIS 
 
 poliomyelitis. It is only of late years that the former diseases have been 
 recognized as arising from the same cause, whereas for many years a purely 
 artificial distinction was made between them. 
 
 In the year 1885 he writes : — 
 
 Both diseases tend to attack previously healthy children in infancy. 
 They present a stage of acute invasion in which they can scarcely be 
 differentiated; this leaves a paralysis behind it which in both diseases 
 affects the motor tracts, in the case of poliomyelitis the grey matter of the 
 cord, in the case of the hemiplegic palsies undoubtedly the brain ; this 
 resultant palsy is naturally of different kinds, but the differences are due 
 merely to the localization of the disease and not to any difference of the 
 essential nature of it. In any case the analogy between the two diseases 
 is remarkable in that in both cases it is the grey matter which is affected. 
 That in the hemiplegic cases the cortex of the brain is affected is proved 
 by the distribution of the paralysis, the occurrence of epileptic attacks and 
 athetosis afterwards, and, from the anatomical aspect, by the results of 
 microscopical examination. In these cases porencephaly is found which is 
 not of the kind present in cases of congenital defect, but which still shows 
 evidences of its inflammatory origin; further, this porencephaly is found 
 in the central convolutions, that is to say, in the motor regions. The 
 appearances are precisely similar to those found in the anterior horns after 
 an attack of poliomyelitis. There is at present no record of pathological 
 investigation of the acute stage of either disease. 
 
 It seems to me to be justifiable to class acute encephalitis as a by no 
 means rare variety of acute anterior poliomyelitis. Personally, I lean 
 towards the opinion that the two diseases are of the same essential type, 
 or are even identical, inasmuch as both are due to the same agent, possibly 
 of an infective nature, which attacks sometimes the grey matter of the cord 
 and at others the cerebral cortex. In order to express this relationship in 
 the nomenclature, I should recommend that this particular form of hemi- 
 plegia should be called cerebral infantile paralysis or polioencephalitis 
 acuta in contradistinction to spinal infantile paralysis or poliomyelitis 
 acuta. The diagnosis of the former is arrived at easily by means of careful 
 investigation ; at the same time the existence of hemiplegia in children 
 due to other causes must not be lost sight of. 
 
 These different observations prepared the way for Medin. The 
 first great Swedish epidemic enabled him to place on a firm basis 
 the relationship between the various types of this disease, which 
 until then had been classed as strictly separate entities. He 
 observed not only the classical spinal form as well as the cerebral 
 and the polyneuritic forms (thereby confirming the brilliant theory 
 of Strumpell), but also the bulbar form and cases of a peculiar 
 ataxia. All these could be traced as occurring" in considerable 
 numbers within the same epidemic, and so were doubtless due to 
 the same cause. Heine's classical description of the simple spinal 
 form was thus amplified; the disease appeared to be one attacking 
 the whole nervous system in a patchy, disseminated manner, and 
 producing, according to its particular localization, a kaleidoscopic 
 variety of clinical pictures. At the Berlin Congress, where Medin 
 published his results, Heubner recognized at once their fundamental 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAN 1 3 
 
 importance. Medin, the first to have the opportunity of observing 
 the acute stage of the disease, thus became the founder of the 
 symptomatology of this stage. 
 
 Medin to Wickman. — In the following- years there occurred 
 several smaller epidemics which enabled Medin's observations to 
 be confirmed. Hoffmann, in 1894, observed a brother and sister, 
 the one suffering from the spinal, the other from the cerebral form. 
 Calabrese also identified the cerebral and spinal types. Zappert 
 observed the Austrian epidemic of 1898 and found an increasing- 
 number of cerebral cases. 
 
 Besides many confirmatory observations, there were many 
 which opened up new ground. Duquennoy (1898) noted a particu- 
 larly painful type. Schultze, Auerbach, also Caverley and Macphail 
 in an epidemic, noted the frequent involvement of the meninges; 
 unfortunately, these observers fell into the error of confounding 
 the disease with cerebro-spinal meningitis. 
 
 The clinical studies of \\ lckman form the completion of this 
 period. By his wonderful histological work he made important 
 additions to our knowledge and he described a meningitic form, 
 also a type simulating Landry's disease and particularly an abortive 
 form of the disease. His work was fully corroborated during the 
 epidemics of 1908 and 1909 by Leegaard in Norway and by Zappert 
 in Austria; Eduard Miiller made an exhaustive clinical study of 
 the epidemic in Hesse. 
 
 The names Heine, Medin, and Wickman mark the commence- 
 ment of three important periods in the history of our knowledge 
 of this disease. 
 
 II.— THE SYMPTOMATOLOGY IN MAN. 
 
 I have neither the intention nor the capacity to give a complete 
 description of the symptomatology. I intend to give merely a 
 short sketch of the subject as worked out by Wickman and Eduard 
 Muller. in order that the reader may be in a position to institute 
 direct comparisons with the clinical picture seen in the case of 
 apes, which I shall describe later. For more complete information 
 I refer the reader to the monographs written by Wickman and 
 Eduard Muller. 
 
 Period Of Incubation. — This lasts at least five days; it is 
 usually not more than ten days, and its average duration is about 
 a week. W r ickman suggests the possibility that it may last only 
 one day, but his conclusion rests upon an inadequate interpretation 
 of certain epidemiological observations. I may mention here that 
 the incubation period in apes may be much longer and that this 
 may be the case also in man. 
 
 Prodromal Symptoms. — The disease does occur suddenly with- 
 out any prodromal symptoms (the " paralysis of the morning "), 
 but this is exceedingly rare; usually, there are symptoms for a 
 variable length of time, one to seven days. The most common 
 
14 EPIDEMIC INFANTILE PARALYSIS 
 
 is fever of no great degree, which is sometimes remittent, some- 
 times continuous. The degree of fever and the severity of the 
 prodromal symptoms generally bear no relation to the amount 
 of subsequent paralysis. The frequency of the pulse is increased, 
 and more than proportionately to the temperature; Eduard Miiller 
 suggests that this may be due to implication of the bulbar centres. 
 Finally, there is general malaise. Occasionally a rash is seen, very 
 rarely herpes labialis (an important differential point with regard 
 to cerebro-spinal meningitis) and herpes zoster. Some authors 
 are inclined to include herpes zoster as one type of the disease; 
 we shall return to this point later. 
 
 Quite frequently the respiratory tract is affected; the patient 
 suffers from coryza with conjunctivitis, from bronchitis or even 
 from broncho-pneumonia. In some epidemics, e.g., in our Hessian 
 one, the respiratory tract is much more frequently involved than 
 the alimentary tract, which in other epidemics is a favourite seat 
 of the initial symptoms; vomiting, diarrhoea or constipation may 
 occur. Examination of the blood shows leucopenia (Eduard 
 Miiller), which is of much diagnostic value in certain cases. 
 
 The most important' prodromal symptoms are those connected 
 with the nervous system. \\ "ithout any definite psychical disturb- 
 ance there is a certain degree of somnolence: rarely convulsions 
 and tremors occur (they are noted more frequently by the older 
 writers): of particular importance is a general tenderness of the 
 whole person: this is characteristic and was observed by Heine, 
 Duchenne, and others. Even a light touch causes pain which is 
 increased by passive movement, particularly if the spine be involved 
 in the movement. Spontaneous pain occurs in the limbs and in 
 the neck and back; the spine feels stiff. There may be some 
 tenderness to pressure of the nerve trunks. The cause of most 
 of the sensory symptoms lies in the involvement of the pia mater. 
 Excessive sweating is a characteristic and has been observed by 
 many authors; Miiller has found it in three-quarters of his cases; 
 it may be due to invoh'ement of the spinal sweat centres, which 
 are said to exist in the anterior horns of the grey matter. 
 
 It may be said that the initial symptoms present no definite 
 diagnostic picture; according to the predominance of any one group 
 of symptoms, the appearances may be meningeal, gastro-intestinal. 
 respiratory, or merely generally febrile in type. 
 
 Stage of Paralysis. — This stage is characterized by an extra- 
 ordinary variety of symptoms. The following classification of 
 types, as proposed by Wickman. cannot be made to fit every case. 
 because so many are intermediate between two types. It has been 
 suggested that Wickman' s classification should be simplified, but 
 I cannot see any good reason why this should be done. 
 
 (a) Abortive Type. — Some of the earlier authors, Briegleb. 
 Pasteur, Aledin. and Leegaard. observed cases of general fever 
 which were in close contact with cases of definite infantile paralysis; 
 but it was Wickman who first clearly proved the connection 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAX 15 
 
 between the two groups of eases and brought into prominence the 
 abortive type of the disease. This type consists essentially of the 
 prodromal symptoms, which clear up without any paralysis. Cases 
 do occur which lie between the true abortive and the spinal type; 
 in these there may be a slight temporary weakness of one muscle 
 or group of muscles, or there may be merely a temporary loss 
 of a deep reflex — the " rudimentary poliomyelitis " of Eduard 
 Miiller. 
 
 The proportion of abortive to paralytic cases varies in different 
 epidemics and in the several foci of the same epidemic. Wickman 
 himself has recorded figures varying from 35 per cent, to 56 per 
 cent. Miiller believes that about 50 per cent, of all cases are 
 abortive. The etiological identity of the abortive and paralytic 
 cases is proved by the simultaneous occurrence of both types 
 in the same family, and latterly by the serum test (vide 
 Chapter VI). 
 
 (b) Spinal Types. — These, forming the classical spinal infantile 
 paralysis, together with the abortive type, make up the great bulk 
 of the cases. They are characterized by the occurrence of paralysis 
 either during or subsequent to the febrile attack. At first there is 
 only paresis, but this quickly develops into paralysis. The extent 
 of the paralysis, the muscle groups involved, and the degree of 
 loss of function, all vary within very wide limits. Most frequently 
 the lower limbs are attacked, particularly the peronei and the 
 quadriceps, next often the shoulder muscles. The muscles of the 
 buttocks, which are involved in two-thirds of the cases, according 
 to Eduard Miiller, and the abdominal muscles are often affected 
 but frequently overlooked. Xot infrequently the intercostals are 
 attacked, the diaphragm more rarely, and the muscles of the back 
 and neck least of all. In short, any and every muscle may be 
 affected, but those of the lower extremities most frequently of all. 
 The paralysis is of the flaccid type, the tone of the muscles being 
 diminished; the deep reflexes are depressed or abolished; the 
 electrical reactions show quantitative diminution of excitability and 
 a partial or complete reaction of degeneration; muscular atrophy 
 follows on the paralysis. At the commencement of the illness there 
 may be an increase in the deep reflexes; Forster has even recorded 
 the occurrence of ankle clonus. Midler considers that involvement 
 of the pyramidal tracts is indicated hereby. The fact that flaccid 
 paralysis does not occur is therefore of no diagnostic significance 
 in excluding Heine-Medin disease. The degree of paralysis may 
 vary from the mere loss of a deep reflex to the most complete 
 flaccid paralysis. 
 
 Disturbances of micturition are rare during the paralytic stage, 
 bur a form of retention which is undoubtedly nervous in origin is 
 frequent in the acute stage (Miiller). Incontinence of either urine 
 or fseces is exceedingly rare. 
 
 The essential characteristic of the disease is therefore a 
 motor paralysis. Disturbance of sensation is of relatively small 
 
i6 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 importance. Loss of sensation to a greater or less degree has been 
 observed, and Miiller lays stress on relative thermanssthesia and 
 analgesia occurring' frequently, if only transitorily, at the beginning 
 of the disease; this may be due to some involvement of the posterior 
 horns. 
 
 The stage of repair follows that of acute paralysis, and after 
 about one to one and a half years the chronic stage begins. After 
 
 Fig. i. 
 
 The spinal form of Heine-Medin disease with paralysis and atrophy of 
 the left upper extremity dating from infancy. The muscles of the shoulder- 
 girdle are most affected. (After Byrom Bramwell.) 
 
 this no further recovery of power is to be expected, and in young, 
 growing individuals it is during this stage that deformities appear. 
 There are also vasomotor disturbances, the limbs are cyanosed and 
 cold and the muscular atrophy becomes marked (fig. i). 
 
 The most common deformities are pes cavus and in children 
 scoliosis (figs. 2 and 3). 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAN 
 
 17 
 
 Occasionally there is a recurrence of the disease occurring- at 
 an interval of some weeks or even months after the first attack 
 (Medin, Leegaard, Neurath, Schwarz). But Miiller has pointed 
 out that every increase of paralysis occurring after an interval is 
 not to be regarded as a recurrence of the primary disease, but is 
 often due to tracts or centres which were damaged suddenly 
 refusing to work. 
 
 (c) A Type which simulates Landry's Disease. — I have already 
 mentioned certain isolated records of cases which point to the 
 identity of Heine-Medin disease and Landry's disease. In the 
 year 1859, Landry described a disease which began as a paralysis 
 
 Fig 
 
 Fig 
 
 The spinal form of Heine-Medin disease with extensive paralysis and 
 deformity. (After Johannessen.) 
 
 of the limbs and rapidly progressed to a fatal issue by involving 
 the medullary centres. The history of this disease furnishes a 
 good example of the way in which an arbitrary and narrow 
 classification may prevent the recognition of wide and important 
 relationships between diseases. Observers overlooked the fact, 
 which was clear from the identity of the anatomical findings, that 
 Landry's paralysis was only " infantile paralysis " with a fatal issue; 
 further, that fatal cases of infantile paralysis ran the same clinical 
 course as cases of Landry's paralysis. As Wickman said, they 
 2 
 
l8 EPIDEMIC INFANTILE PARALYSIS 
 
 appear to have made the death of the patient the essential feature 
 of the diagnosis. During the Swedish epidemic, Wickman was 
 able to convert the probability of the identity of the two diseases 
 into a certainty. The basis of this type is a " poliomyelitis 
 acutissima," beginning in the centres for the lower limbs, spread- 
 ing rapidly to those for the upper limbs and leading" to a fatal 
 issue in a few days by involving the centres in the medulla. In 
 a few cases the arms are affected first, the paralysis being simul- 
 taneously ascending and descending. 
 
 (d) Bulbar and Pontine Types. — Medin was the first to call 
 attention to the frequency with which the cranial nerves were 
 attacked. It is rare to see them involved alone; usually the spinal 
 centres are affected at the same time. The facial nerve is the one 
 most frequently paralysed, generally on one side only and in its 
 whole distribution. With it is associated sometimes the hypo- 
 glossal (figs. 4 and 5). 
 
 Fig 4. Fig. 5. 
 
 The bulbar form of Heine-Medin disease with paralysis of the left facial 
 and hypoglossal nerves. In fig. 5 the patient is trying to close both eyes. 
 (After Wickman.) 
 
 More rarely the abducens and the motor oculi are involved, 
 and occasionally the trochlear nerve. Nystagmus has been 
 observed by Medin, Miiller, and Netter. The optic nerve has been 
 affected; the trigeminal, as shown by paralysis of movements of 
 the lower jaw, and very rarely the other cranial nerves. The 
 clinical picture is extraordinarily variable, according to the particular 
 nerves affected, the degree of their paralysis and the amount of 
 involvement of the spinal cord which is present. Of course, all 
 isolated palsies of cranial nerves are not due to Heine-Medin 
 disease and in such cases serum diagnosis is of great importance 
 (vide Chapter VI). 
 
 (e) Cerebral Type. — Striimpell maintained the identity of cer- 
 tain encephalitic processes with epidemic poliomyelitis. Medin 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAN 19 
 
 confirmed his views, but they were not generally accepted owing 
 to the rarity of observations on cerebral cases. At the present 
 time there can be no doubt of the existence of such cases. Patho- 
 logical encephalitic lesions quite analogous to those found in the 
 spinal cord have been seen, and during epidemics spastic and flaccid 
 cases have been observed side by side by Mobius, Medin, Buccelli, 
 Hoffmann, Leegaard, Eduard Miiller, Zappert, Spieler, Schlesinger, 
 Nonne, and Krause; they have been observed in the same patient 
 by Williamson. Neurath, Calabrese, Oppenheim, Pierre Marie, 
 and Wickman. The serum diagnosis is of value both in 
 proving the existence of encephalitis due to Heine-Medin disease 
 as also in differentiating that from encephalitis due to other 
 causes. 
 
 {f) Ataxic Type. — Medin first described ataxia similar to that 
 seen in Friedreich's disease, also Wickman, Zappert, Spieler, 
 Lindner and Mally, Netter, Nonne, and others. Zappert does not 
 consider it advisable to make a special ataxic group; he prefers to 
 classify such cases in the pontine group. Wickman, on the other 
 hand, holds that all the ataxic cases are not due to a lesion in the 
 pons or medulla, but that some are caused by lesions of the 
 cerebellum, the mid-brain or Clarke's column. 
 
 (g) Polyneuritic Type. — This was recognized first by Medin, 
 and later by many other observers. It is doubtful, considering the 
 absence of sensory signs, whether the process involved is a true 
 neuritic one. Its existence is not definitely proved, but the amount 
 of work which has been done in this connection is not large. This 
 type could be explained by involvement of the central nervous 
 system. On clinical grounds the retention of this type is justifiable, 
 and later a simplification may be possible. 
 
 (Ji) Meningitic Type. — The meningitic form is that in which 
 the symptoms due to involvement of the pia mater are the most 
 prominent; such are vomiting, headache, pain in the neck, pain and 
 stiffness in the spine, and a slight degree of opisthotonos. We owe 
 it to Wickman that such cases were recognized as belonging to 
 Heine-Medin disease. Formerly they were classed as cerebro- 
 spinal meningitis occurring with infantile paralysis, and it was even 
 suggested that cerebrospinal meningitis and infantile paralysis w r ere 
 one and the same disease. Later epidemics have led to Wickman's 
 view being upheld. Xetter found that 29 per cent, of his cases 
 belonged to the meningitic type. Lhermitte, as late as 1909, 
 assumed a close relationship between infantile paralysis and cerebro- 
 spinal meningitis, and he also denied the connection between 
 epidemic infantile paralysis and Landry's disease; but he is almost 
 the only observer who holds such views. 
 
 Prognosis. — For many years Heine's dictum held good, that 
 the prognosis quoad vitam was good, but the prognosis quoad 
 sanationem bad. At the present time, owing to the researches of 
 Wickman, we would rather invert Heine's prognosis. 
 
 The mortality in different epidemics and within the same 
 
20 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 epidemic varies immensely. Wickman found the figure to vary 
 between 10 per cent, and 42.3 per cent. 
 
 Wickman ... 
 
 Leegaard 
 Zappert ... 
 Lindner and Mally 
 Fiirntratt 
 Krause ... 
 Ed. Muller 
 Peiper 
 Eichelberg 
 
 Sweden, 1905 
 Norway, 1905 
 N. Austria, 1908 
 E. Austria, 1908 
 Steiermark, 1908 
 Westphalia, 1909 
 Hesse-Nassau, 1909 
 Pomerania, 1909 
 Hanover, 1909 
 
 Total number 
 
 of cases with 
 
 paralysis 
 
 868 
 
 577 
 266 
 
 7i 
 433 
 633 
 100 
 
 51 
 34 
 
 Mortality 
 
 16.7 per cent. 
 
 14.56 
 
 10.8 
 
 22.5 
 
 13.6 
 
 12.3 
 
 16 
 
 11. 7 
 
 20.58 
 
 In this table the mortality figure is in relation to the cases with 
 paralysis only; the abortive cases are not included. 
 
 In general the fourth and fifth days are the most dangerous. 
 There is further a marked difference between the infantile and the 
 adult cases. Wickman found: — 
 
 In children up to 11 years — Mortality 10.5 per cent. 
 In patients above 11 years — Mortality 27.6 per cent. 
 
 The statistics of other authors show a similar result. 
 
 In connection with the prognosis quoad sanationcm the rela- 
 tionship between the transitory abortive type and the types with 
 paralysis has already been mentioned. 
 
 Recovery from paralysis, which was specially emphasized by 
 Neurath in 1901, occurs in at least 20 per cent, of all cases 
 (Wickman). 
 
 In this respect also there is a great difference between children 
 and adults. 
 
 Wickman gives the following : — 
 
 In patients 9 to 11 years old — 48.4 per cent. 
 In patients above 11 years old — 32.2 ,, 
 
 Leegaard finds : — 
 
 In patients up to 14 years — 30.4 per cent, recovery 
 In patients above 14 years — 22.2 ,, ,, 
 
 The prognosis is from every point of view worse in adults than 
 in children. 
 
 Sporadic Infantile Paralysis. — Finally, let us consider the so- 
 called sporadic type. The more recent writers have not only con- 
 sidered the identification of these cases with epidemic infantile 
 paralysis doubtful, but have denied this identity. They do this on 
 the ground that the clinical picture is quite different in the two 
 cases, the paralysis sets in suddenly without any prodromal sym- 
 ptoms, and the cases occur in a totally isolated way. It must 
 
THE SYMPTOMATOLOGY OF THE DISEASE IN MAN 21 
 
 be remembered, however, that no case of sporadic poliomyelitis has 
 been recorded to which a counterpart cannot be found among 
 epidemic cases. Other undoubtedly infectious diseases occur in a 
 sporadic manner, e.g., meningitis and scarlet fever; further, it is 
 doubtful whether so-called sporadic cases are ever really sporadic, 
 owing to the fact that the associated cases, being abortive, are over- 
 looked. It has been maintained that the prognosis is different in 
 the two groups, that death and recovery from the paralysis never 
 occur in sporadic cases. But this means merely that the fatal cases 
 have been called " Landry's paralysis," and those which recover 
 have been called " polyneuritis," that the difference depends upon 
 an arbitrary nomenclature. However, at the present time no doubt 
 can exist, as the identity of the disease in the sporadic and the 
 epidemic forms is proved by means of the serum test. 
 
CHAPTER III. 
 
 Etiology of the Disease. 
 
 I.— MICROSCOPICAL AND CULTURAL 
 RESEARCHES WITH EXPERIMENTS ON 
 
 ANIMALS, 
 
 The older Views. — The disease is even now sometimes called 
 "paralysis during dentition" in England. The views of Marshall, 
 Kennedy, and others appear seemingly still to have some adherents, 
 though probably this is only apparent; they blamed difficult denti- 
 tion as the cause of Heine-Medin disease. At the present time we 
 cannot pass by this theory without some recognition, particularly as 
 a larger clinical experience and, before all, experiments on animals 
 have taught us that the mucous membrane of the mouth, nose, and 
 throat is a frequent point of entrance of the virus; and, moreover, 
 as these older physicians associated the beginning of the disease 
 with disturbance of the intestinal canal. In the oldest observations 
 therefore we find the same points of entrance indicated, which we 
 still regard as the most important. It was from the English 
 writers that Heine took his idea that difficult dentition lay at the 
 root of the trouble; or at any rate he was supported by them in his 
 theory. Such an assumption was in accordance with the spirit of 
 the times ; men sought rather for endogenous than for exogenous 
 causes of disease. The disturbances which accompany dentition 
 together with the great developmental activity occurring at the 
 same time in the central nervous system formed, according to 
 Heine, a sufficient cause of irritation of the delicate nervous 
 system; an additional proof was found in the fact that inflammation 
 of the brain and spinal cord occurred most frequently during these 
 years. Although we cannot accept Heine's theory in its entirety 
 to-day, we must admit that there was some justification for it; we 
 ourselves know no reason why Heine-Medin disease attacks 
 children specially, and occurs in certain years of childhood more 
 than in others. In his theory as to pathogenesis Heine compels 
 admiration for his acumen. He was strongly opposed to the theory 
 that the disease was hereditary or due to a defect in development; 
 this theory was certainly a convenient explanation, so convenient 
 
ETIOLOGY OF THE DISEASE 23 
 
 that up to quite recent times it has appeared in the text-books. 
 Taking' into consideration the state of medical knowledge of his 
 time we must admit that his reasoning was not lacking in clarity. 
 The twenty years after Heine's monographs produced nothing of 
 importance. One reason for this may be found in the rise of the 
 French theory of an "essential" or "idiopathic" infantile para- 
 lysis; this tended to make inquiry into the cause of the disease 
 appear unnecessary, even when pathological investigation had 
 proved that such a term as " essential " was quite unjustifiable. 
 
 Striimpell's Hypothesis. — We owe it to the broad view of the 
 subject taken by the great clinicians Strumpell. Seeligmuller, and 
 Pierre-Marie that once more attention was drawn to the subject of 
 the etiology of the disease. The direction in which they moved 
 proved to be at once definite and fertile of result. They started 
 from the clinical observation that the whole clinical picture of the 
 disease, particularly in its early stages, showed great similarity 
 with other diseases which were produced certainly by infection 
 from without. Further, that cases which appeared to be sporadic 
 could be arranged in groups, and consideration of the question 
 whether the disease was not only infectious but even contagious 
 became imperative. I cannot do otherwise than quote some of 
 the more pregnant of Strumpell's dicta. In 1884, i n his thesis, 
 Strumpell discusses the etiology of some of the diseases of the 
 nervous system. He says: "Passing in review the other nervous 
 diseases from this point of view, one group stands out by itself, 
 the members of which show great similarity with one another in 
 their course and in their symptomatology. This group consists of 
 the acute multiple neuritis, acute poliomyelitis and acute encephal- 
 itis of children. All have a sudden onset accompanied by con- 
 siderable fever. The patients show mental dulness, suffer from 
 headache, gastric disturbances, and occasionally enlargement of 
 the spleen, swelling of the joints, and a slight albuminuria. 
 According" to our present point of view these are all signs of 
 infection by a pathogenic organism."* 
 
 In another place Strumpell says: "The peculiar clinical 
 appearances of spinal infantile paralysis have frequently given rise 
 to the opinion that in this disease we have to deal with an acute 
 infective process. As in the case of so many undoubtedly infec- 
 tious diseases, we cannot prove this to be so by direct demonstration 
 of the causative agent. At present we can rely only upon the 
 following facts: The peculiarity of the clinical course: the sudden 
 onset for which no obvious cause is present; the moderately high 
 temperature; the severity of the general symptoms; finally, the 
 nature of the changes found in the spinal cord, which point unmis- 
 takably to a truly inflammatory process." 
 
 Seeligmiiller and Pierre Marie bring forward similar arguments 
 to prove that the disease is due to a specific infection. How little 
 
 * In the original not italicized. 
 
24 EPIDEMIC INFANTILE PARALYSIS 
 
 general acceptance was given to these arguments is proved by the 
 rejection of the theory of infection by so important an authority as 
 Dejerine even as late as the year 1888; he maintained that clinically 
 and pathologically the disease belonged to the group of system 
 diseases. 
 
 Nevertheless, when on the report of an epidemic (about 1881) 
 there followed more and more announcements of epidemics of 
 infantile paralysis, the probability of an infective basis of the 
 "disease became greater, and from that time dates the era of active 
 etiological investigation along bacteriological lines, particularly 
 after the publication of Medin's famous investigations in 1890. 
 
 Microscopical and Cultural Investigation. — Attention had 
 already been directed to the spinal cord as possibly harbouring 
 bacteria. Goldscheider in 1893 had stained the cord of an acute 
 case with methylene blue and by Gram's method, and failed to find 
 any bacteria. Siemerling and Dauber obtained similar negative 
 results ; their negative findings were confirmed repeatedly by other 
 observers. These results, obtained by using well-recognized 
 bacterial stains, made observers chary of accepting later positive 
 findings obtained by means of cultural methods. By some the 
 difficulty was overcome by assuming that bacteria were destroyed 
 very rapidly in the grey substance of the cord. 
 
 The Era Of Cocci. — Schultze, by describing a case which 
 clinically gave evidence of considerable involvement of the men- 
 inges, began this era which I have called the era of cocci, because 
 of the nature of the organism which was found. He found, on 
 examination of the lumbar puncture fluid, " many diplococci, 
 arranged in rows, similar to gonococci but having the appearances 
 of the meningococcus of Weichselbaum and Jager." It was 
 remarkable that all attempts to culture these organisms failed, 
 although they were numerous, and although cultures were made 
 from other samples of the lumbar puncture fluid. Upon these 
 facts Schultze constructed a theory of the identity of meningitis 
 and poliomyelitis; he regarded the two diseases as due to different 
 localization of the same morbid agent. 
 
 Following on this, many positive results were obtained by 
 bacteriological examination, and it appears as though the discovery 
 of Schultze had exercised a certain influence upon later observers. 
 Bulow-Hansen and Harbitz (in 1898) also found a Gram-positive 
 diplococcus in the cerebrospinal fluid, but do not lay much stress 
 upon their discovery on account of the very numerous negative 
 results which they obtained. Courmont and Bonne (1899), Concetti 
 (1900), Dercum (1900), Looft and Dethloff (1901), Gossage (1902), 
 Engel (1900), Spiller (1903), Batten (1904), Barnes and Miller (1907) 
 all found micro-organisms which were considered to be meningo- 
 cocci in some cases, pneumococci or staphylococci in others. These 
 results served to strengthen the theory of the microbial origin of 
 the disease. Giersvold's observations during the first great Nor- 
 wegian epidemic in 1905 and 1906 caused a considerable sensation; 
 
ETIOLOGY OF THE DISEASE 25 
 
 he found Gram-positive cocci shaped like beans and forming short 
 chains, which he believed to be identical with the Jager meningo- 
 coccus. These organisms grew on the ordinary culture media. 
 Harbitz and Scheel were obviously influenced by these results; they 
 also found cocci in the cerebrospinal fluid, but reserved judgment 
 as to their exact etiological significance. 
 
 A study of the literature shows that in no case has any clear 
 proof of the causal significance of the cocci observed been brought 
 forward; further, the bacteria seen have been of the most various 
 kinds, they have been observed only in isolated cases, and no inocu- 
 lation experiments have been made with any of them. 
 
 The Accumulation of Negative Results. — Doubts as to the 
 importance of the few positive results become much greater when 
 we compare them with the vast number of negative results obtained. 
 Guinon and Rist in 1903 found the cerebrospinal fluid of an epidemic 
 case to be sterile, and with the advent of the larger epidemics in 
 Scandinavia (1905-1907), North America (1907-1908), Austria (1908- 
 1909), Germany (1909J, and France (1909) the negative evidence has 
 become overwhelming. In Sweden Wickman and Jundell not only 
 found eight perfectly fresh specimens of lumbar puncture from 
 different cases sterile, but also all material obtained from autopsies 
 on cases of epidemic Heine-Medin disease. Ellermann also 
 obtained only negative results, but fell into the error of proclaiming 
 certain rhizopods to be the cause of poliomyelitis; his statements 
 did not hold good in the face of criticism. In America the results 
 obtained by many experimenters were all negative — Purkins and 
 Dudgeon, Sherman and Spiller, Greene, Wilson and Rothrock, 
 Thomas, Taylor, Hoch, Wollstein, Starr, and Stephens. For 
 example, out of 226 cases Stephens obtained a culture in only seven 
 cases, and these he recognized definitely as contaminations. There 
 were no positive results in France. The first observers had found 
 cocci which were in no way difficult of demonstration or of culture, 
 and this gave further importance to the consistently negative results 
 obtained from a far greater material, and led to the opinion that 
 the original discoveries were due to errors in technique. One such 
 error was explained by Leiner and v. Wiesner, who found that if 
 only the first portion of the lumbar puncture fluid was used a 
 growth of cocci could be obtained fairly frequently, but never from 
 the rest of the fluid; they carried out the same experiment in the 
 case of diseases other than infantile paralysis, and obtained the 
 same result, thus proving that the positive results were due to mere 
 contamination, probably from the skin of the patient. They also 
 pointed out the danger of using broth cultures in this connection, 
 because bacteria will flourish in the broth without giving any indi- 
 cation of the number originally present. Koch's axiom is still 
 more or less justified, namely, that for proof of the etiological 
 significance of any organism it must be shown to be present in a 
 quantity proportionate to the severity of the clinical signs. 
 
 So far, therefore, the history of the search for the cause of 
 
26 EPIDEMIC INFANTILE PARALYSIS 
 
 Heine-Medin disease is a succession of mistakes. A short historical 
 retrospect is not without its advantages if we learn from it the 
 great danger of accepting any results in a scientific inquiry with 
 undue haste. I have alluded above to my own impression, that it 
 was the expressed or unexpressed underlying conviction that epi- 
 demic infantile paralysis was only a form, differently localized, of 
 epidemic cerebrospinal meningitis which led observers to consider 
 bacteria as the cause of a disease which we know now has nothing 
 to do with them. The experiments carried out under these con- 
 ditions only confirmed them in their view. At this point I would 
 draw attention particularly to Wickman's conclusions; at a time 
 when nothing was known for certain of a non-bacterial cause of 
 the disease, and when there were many adherents of the theory of 
 the identity of meningitis and poliomyelitis, he stated definitely, on 
 the basis of thorough pathological, clinical, and epidemiological 
 investigation, that if cocci were really the cause of both diseases 
 they must be fundamentally biologically different in the two cases. 
 
 Personal Bacteriological Research, — I cannot deny that when 
 I began to study this disease at a time when my clinical, patho- 
 logical and epidemiological experience was limited, I was under the 
 influence of the hypothesis that meningitis and infantile paralysis 
 might be identical, or, at any rate, related diseases; as a result, in 
 my first bacteriological experiments I devoted my energies to the 
 finding of cocci. Owing to the fact that in our Hessian epidemic 
 the respiratory tract was the site of the prodromal symptoms, 
 whereas in the Westphalian epidemic studied by Krause it was the 
 alimentary tract which suffered first, I was led to make cultures 
 from the pharynx and tonsils. The results disclosed the ordinary 
 organisms; in the first experiments I found pneumococci to be 
 somewhat in excess of normal, and in the later cases the staphylo- 
 coccus albus; under the influence of the above-mentioned hypo- 
 thesis I spent considerable time in investigating the latter organ- 
 isms. On turning my attention to the cerebrospinal fluid the 
 problem became clearer; specimens were obtained from chronic, 
 very acute, severe, and slight cases, and always the result was 
 negative. The specimens were quite clear; vigorous centrifugali- 
 zation gave not a trace of deposit; with the microscope a few 
 lymphocytes were seen; an organic virus was not seen either in 
 stained or in unstained specimens. The stains used were of the 
 most various kinds, the usual aniline dyes. Gram's stain, Ziehl's 
 stain for Bacillus tuberculosis, Giemsa's stain. Many culture media 
 were used : Bouillon, gelatine, agar, glycerine-agar, g"rape-sugar- 
 agar, ascites-agar, agar with the addition of the sera of different 
 animals, coagulated serum, &c. Equal parts of lumbar puncture 
 fluid and bouillon were mixed and incubated at a temperature of 
 37° C. The result of the tests was that the tubes remained sterile 
 except in a few instances. The growth in these cases could be 
 identified always as a common contamination. Examination of the 
 blood in a severe case led to the same result. 
 
ETIOLOGY OF THE DISEASE 27 
 
 It must be admitted that these experiments, together with the 
 results obtained by others, did net furnish proof that the disease 
 was not caused by a micro-organism; it was not known for certain 
 whether the virus existed in the blood or in the cerebrospinal fluid; 
 indeed, later experiments on animals have shown that the virus 
 exists at most in extremely small quantities in either of these fluids. 
 Certainty could be attained only after examination of the central 
 nervous system, in which a living virus, if present at all, would be 
 found. 
 
 The material I used for this investigation was obtained from 
 children who had died from the effects of a typical attack of Heine- 
 Medin disease. The details of the cases I will give later when 
 describing the experiments on animals. Cultures were made from 
 the brain, the pons, and the spinal cord, which were placed at my 
 disposal by Professor Beneke. The tubes remained sterile except 
 in a few instances of contamination. Careful search in stained 
 sections revealed no bacteria although the pathological appearances 
 were typical of poliomyelitis. Inasmuch as the later experiments 
 on animals proved that the virus was present in large amount in 
 the affected portions of the nervous system I was able to state with 
 confidence that it was impossible that a microbe which could be 
 stained and cultivated easily could be tlic active agent in the causa- 
 tion of epidemic infantile paralysis. 
 
 I have mentioned already the researches of Wickman which 
 had led to the same result; there followed the work of Landsteiner, 
 and particularly the wide researches of Krause and Meinicke, who 
 throughout the whole Westphalian epidemic never found any 
 bacteria which could be regarded as playing a part in the etiology 
 of the disease. 
 
 All these researches, of great importance but all negative, 
 brought about unanimity of opinion in 1909 that a bacterial cause 
 of Heine-Medin disease does not exist; it was like a voice from 
 the past when Pottpeschnigg in October, 1909, announced the dis- 
 covery of a coccus with some claims to be considered pathogenic, 
 but he very soon acknowledged that the coccus was merely a con- 
 tamination. 
 
 Important Microscopical Findings. — Although ordinary bac 
 teriological methods were thus proved unavailing it was not thereby 
 made certain that the microscope and culture tubes would not ulti- 
 mately yield results. As will be demonstrated later, the virus 
 belongs to the variety which is capable of passing through the 
 filters of Berkefeld, Chamberland, and Pukall, which keep back 
 ordinary bacteria. Starting" from this fact it was necessary to seek 
 the virus in filtrates which were free from the normal cellular 
 constituents of brain and spinal cord. With Joseph and Siebert I 
 examined such filtrates by means of the ultramicroscope. We 
 found very small, oval, slightly illuminated bodies which were 
 motionless or showed only Brownian movements; they attracted our 
 attention because we did not find them in filtrates of normal brain. 
 
28 EPIDEMIC INFANTILE PARALYSIS 
 
 From experience gained in previous ultramicr.oscopic investigations 
 of proteins we were able to exclude the theory that these bodies 
 were due to coagulation of albumin. On the other hand, the 
 appearance of these bodies was not constant enough to enable us 
 to state that they were connected with the disease, or that they were 
 the actual causative agent. The observation is, however, of 
 importance, because Flexner observed similar bodies at a later date, 
 and his description corresponds very closely with our own observa- 
 tions. Flexner says also that he was able to render these bodies 
 visible by means of LdfHer's stain. Levaditi had previously 
 obtained the same result; by means of a " culture " which we shall 
 describe later, he had obtained small rounded bodies which he 
 succeeded in staining by Loffler's method, and also with weak solu- 
 tions of fuchsin; he expressed himself with regard to the interpre- 
 tation of his results in the same guarded way as we had done with 
 ours. Leiner and v. Wiesner assert that they have seen " very 
 small oscillating bodies " in a hanging-drop preparation made from 
 virus-containing filtrate. They also state that they are not con- 
 vinced that the bodies represent the virus itself. 
 
 Specific Intracellular Bodies. — In yet another direction the use 
 of microscopic methods seems to give some promise of success. 
 Wickman has drawn the analogy between poliomyelitis and rabies 
 as a result of his excellent pathological investigations. This 
 analogy becomes only more striking the more the nature of the 
 active agent is considered. Negri has called attention to certain 
 intracellular bodies, which are found only in the ganglion cells in 
 hydrophobia, and are characteristic of this disease. There is still 
 much discussion as to whether these bodies are to be considered 
 the cause of the disease, cellular degeneration products, or merely 
 the capsules of the pathogenic agent which is as yet unknown. 
 Wickman looked for similar intracellular appearances in cases of 
 epidemic infantile paralysis, but failed to find them. However, a 
 recent discovery makes it probable that renewed search is justifiable. 
 Joest has shown that Borna's disease in horses, which occurs in 
 epidemics, is a disseminated, infiltrative myelo-encephalitis; this 
 disease is so similar to Heine-Medin disease in its histological 
 appearances — due allowance being made for difference in localiza- 
 tion, Borna's disease attacking the olfactory lobe, and Heine- 
 Medin disease the grey matter of the anterior horns — that one 
 might almost regard the two diseases as being identical. Joest 
 with Degen, using Mann's method of staining, demonstrated the 
 presence of intranuclear bodies in the ganglion cells in cases of 
 Borna's disease; the nature of these bodies is not understood as 
 yet, but they appear to be specific to the disease. At a meeting of 
 the Medical Society of Marburg (November 3, 1909) I stated my 
 belief that, in view of Joest's and Degen's results, it would be of 
 value to investigate cases of poliomyelitis using the same methods. 
 In spite of most energetic search, however, Joseph and myself have 
 been unable to find any constant intracellular bodies either in 
 
ETIOLOGY OF THE DISEASE 29 
 
 sections or in smear preparations made from human material, or 
 from the brain and cord of infected apes. Leiner and v. Wiesner, 
 Landsteiner and Levaditi have carried out similar researches, and 
 have arrived at the same negative result. 
 
 On the other hand, Bonhoff found bodies included in the nuclei 
 of the glia cells, particularly of the lumbar enlargement, of a case 
 of undoubted poliomyelitis, which bodies he considers specific; they 
 were demonstrated only by using Lentz's modification of Mann's 
 stain applied to sections. The size varied from a very small, red 
 dot to an oval with a diameter of 3 to 4 ^ ; the average size had a 
 diameter of 2 fi. Occasionally as many as five bodies were found 
 in one nucleus; they were surrounded by a clear zone, and the largest 
 of them showed one or two minute granules which stained clearly 
 with the Mann-Lentz method. Similar bodies were found in the 
 nuclei of cells forming the adventitia of the blood-vessels, of the 
 ependymal cells, and in some nuclei of the round-celled infiltration. 
 In specimens made from the spinal cord in normal cases and in 
 other diseases these bodies were not found. Without going into 
 the question whether these bodies represent one form of the cause 
 of the disease, Bonhoff claims that they are abnormal and charac- 
 teristic of Heine-Medin disease. 
 
 " Cultures " Of the Vims. — I said above that attempts to culti- 
 vate the virus of Heine-Medin disease might not be without value, 
 even though one might be of the opinion that the cause of the 
 disease was not a bacterium. It is well known that certain trypano- 
 somes, which are classed usually among the animal organisms, can 
 be grown on specially prepared media. I will at once confess that 
 none of my own attempts have yielded the smallest result, even 
 with the media which Flexner and Lewis described later. These 
 authors at first stated that they had obtained no cultures of what 
 could be considered to be a virus of poliomyelitis ; later they 
 reported certain " cultures " which they claimed to have obtained. 
 They made an emulsion of an infected spinal cord, filtered this 
 through a Berkefeld filter, and added the filtrate to equal parts of 
 ordinary bouillon and of human serum (in some cases the serum of 
 rabbits was used). After a few days they found some opacity in 
 the tubes; when injected into apes these "cultures" produced the 
 typical picture of experimental poliomyelitis. Levaditi confirmed 
 this experiment,' but it proves only that after being kept for a certain 
 time (for fifteen days in Levaditi's case) at a temperature of 37 C. 
 the fluid still contained the active virus of poliomyelitis. The mere 
 fact of virulence does not prove growth of the virus; it may be that 
 the degree of dilution with serum-bouillon was not enough to 
 prevent the activity of the virus, and Flexner and Lewis themselves 
 have proved that it is possible to cause disease and death in apes 
 with much more dilute virus. Flexner and Levaditi state that they 
 obtained a cloudiness in a second series of tubes inoculated from 
 the first, but that from these secondary tubes they were unable to 
 produce the disease in monkeys, so that they themselves are 
 
30 EPIDEMIC INFANTILE PARALYSIS 
 
 cautious in their interpretation of the remarkable appearances 
 observed by them. As we ourselves have never been able to see 
 any clear evidences of growth of the virus in any media, and as 
 Leiner and v. Weisner have had the same experience, it may well 
 be wise to doubt whether the cloudiness observed by Flexner and 
 Lewis can be considered as a culture at all, specially as these 
 authors themselves are exceedingly cautious in so describing it. 
 It may be mentioned that the attempts to intensify the virus in 
 collodion capsules in vivo by Leiner and v. Wiesner have failed 
 also. 
 
 All investigation into the etiology of the disease has shown 
 that the active agent cannot be a bacterium, nor can it be any 
 micro-organism capable of being cultivated easily. We have no 
 evidence which will bear the test of criticism as to the morpho- 
 logical characteristics of the virus. 
 
 Experiments on Animals* — The earlier experiments on animals 
 were few, but caused less confusion than the supposedly positive 
 bacteriological results. At a time when it was still doubtful 
 whether the disease was infectious the aim of all experiments on 
 animals was to find out if any materials would produce myelitic 
 lesions in animals comparable to those of Heine-Medin disease in 
 man. The first experiments were carried out on rabbits, a point 
 on which I would lay particular stress. Roger infected fourteen 
 rabbits intravenously with streptococci, and found that in two to 
 three weeks the animals wasted, and showed marked atrophy in the 
 muscles of the hind limbs almost exclusively, but without any 
 definite paralysis. Histologically changes were found in the 
 anterior horn cells; the number of cells was diminished, they were 
 irregular in shape, and showed vacuolation with degeneration of 
 the nuclei in some cases. The vessels were full and enlarged, and 
 in places there were small haemorrhages. Roger concluded that a 
 more or less systematized myelitis could be caused by an infective 
 agent. In the same year Gilbert and Lion made similar experi- 
 ments on rabbits, using B. coli. In those animals which did not 
 die very shortly paralysis occurred on about the twelfth day and 
 at the same time diarrhoea. In these cases also degeneration of 
 the anterior horn cells and hypersemia were found. Vincent 
 obtained similar results in a rabbit infected with a mixture of 
 bacteria. Thoinot and Masselin in 1894 carried out the most com- 
 plete experiments (Hoche gives a complete bibliography). Out of 
 forty-three rabbits infected with B. coli four died rapidly. The 
 thirty-nine survivors all suffered from paralysis, generally of the 
 hind limbs, with muscular atrophy and general wasting. Rabbits 
 infected with staphylococci were affected in the same way. Vacuo- 
 lation of the anterior horn cells was found but no interstitial change, 
 while the vessels zvere normal. 
 
 Hoche succeeded in producing changes in the spinal cord by 
 direct arterial infection with pneumococci, staphylococci, and 
 B. coli only when at the same time he injected starch or lycopodium 
 
ETIOLOGY OF THE DISEASE 3 1 
 
 granules or some other powdery material which would produce 
 embolic lesions in the cord. In his case the changes were all of a 
 parenchymatous type affecting only the cells and nerve fibres, the 
 blood vessels being affected only very slightly and the interstitial 
 tissues not at all. Homen also failed to obtain any results; he made 
 very numerous experiments with streptococci, injecting them 
 specially into the lymph spaces and intraneurally. Wickman used 
 strains of bacteria which had been passed repeatedly through 
 animals, but he was forced to admit that no definite palsy occurred 
 in any of his animals, although they wasted considerably; his cases 
 on section also did not show the appearances of true poliomyelitis. 
 We must confess that all these experiments produced very little 
 of value in giving an answer to the question whether the changes 
 of poliomyelitis were due to an infective agent. Judging from the 
 descriptions and illustrations given by the various authors, the 
 microscopical changes observed had very little similarity with those 
 presented by the lesions of true poliomyelitis, in spite of the 
 occasional changes seen in the ganglion cells. The characteristic 
 adventitious and perivascular cell infiltration is absent, as also the 
 increase in the number of nuclei, which is so typical in the sections 
 in cases of Heine-Medin disease. If any comparison with a 
 spontaneous disease is permissible it is with progressive muscular 
 atrophy; this disease, however, is certainly totally different in its 
 etiology to Heine-Medin disease. 
 
 Although we cannot lay so much stress on the results of these 
 earlier experiments on animals as was claimed for them at the time, 
 yet they prove one fact very clearly : Bacteria of very different 
 kinds, by whatever route they enter the body, do not tend to 
 produce lesions typical of poliomyelitis. If further proof that 
 bacteria do not cause the disease were needed, the numerous 
 negative results recorded above might be interpreted in that sense. 
 
 A further point is that rabbits are peculiarly liable to suffer 
 from paralyses when any molecular substance is injected into the 
 blood-stream. As we shall see later, this observation is of import- 
 ance when considering the rabbit as an animal for experimental 
 research in poliomyelitis. 
 
 The attempts to produce poliomyelitis in animals by injecting 
 material from the organs of cases of Heine-Medin disease will be 
 further considered below. 
 
 II.— EXPERIMENTAL RESEARCH ON POLIO- 
 MYELITIS IN MONKEYS— CLINICAL HISTORY 
 OF EXPERIMENTAL POLIOMYELITIS. 
 
 Landsteiner's Original Experiment. — In the case of successful 
 research with animals there is a definite point where this branch 
 of the subject begins. Landsteiner, with the aid of Popper, has 
 the credit of having for the first time succeeded in transmitting 
 
32 EPIDEMIC INFANTILE PARALYSIS 
 
 the disease to monkeys. Landsteiner published his results in full 
 in the Zeitschrift fur Immunitatsforschung on April 5, 1909. 
 
 I give a full abstract of his results owing to their great 
 importance : — 
 
 The material used was the spinal cord of a child of 9 years, who died 
 on the fifth day of an attack of typical Heine-Medin disease. An emulsion 
 was made and this was injected into the peritoneum of two monkeys. The 
 first, a young Cynoce-plialus hamadryas, became seriously ill on the sixth 
 day and died on the eighth. At the autopsy the internal organs were found 
 to be normal with the exception of the spinal cord which was seriously 
 affected. The conditions found were : Infiltration of the pia mater of the 
 cord with cells, perivascular infiltration in the grey matter, diffuse infiltra- 
 tion in the grey matter which was disorganized by oedema; the anterior 
 horns were much more affected than the posterior ones. Similar inflam- 
 matory infiltrations were found in the medulla, pons, mid-brain and cortex. 
 The cells of the infiltration were mostly lymphocytes. Where inflammation 
 was present the ganglion cells were much altered, and chiefly in the 
 anterior horns (outline blurred, granular disintegration, vacuolization, nuclei 
 staining poorly, invasion by round cells). 
 
 In the second monkey, a young Macacus rhesus, between the twelfth 
 and seventeenth day paralysis appeared, which became complete in both 
 lower limbs. The changes found were similar but less marked to those 
 obtaining in the first monkey. The ' animal was killed on the nineteenth 
 day. Two more monkeys were injected with emulsion of the spinal cord 
 of this monkey, but the experiment was without result. 
 
 The description given of the illness of the second monkey 
 and of the histological appearances in both cases, also the illus- 
 trations of the histological changes, leave no doubt that Landsteiner 
 and Popper succeeded in producing poliomyelitis in monkeys, which 
 ran a course similar to the disease in man and caused lesions 
 identical from the histological point of view. 
 
 The probability that the disease was caused by a living virus 
 was increased by these experiments and would have become a 
 certainty if the attempt to transmit the disease to a further series 
 of monkeys had been successful. As this failed entirely the 
 possibility was not excluded, that the disease might be transmitted 
 by a non-living agent {e.g., a toxin). Landsteiner and Popper 
 reject this theory on the ground that the histological changes had 
 all the characters of an inflammatory process. They explain the 
 failure of the attempt to transmit the disease further by suggesting 
 that the potency of the virus was diminished by its passage through 
 one animal. We may say at once that another and better explana- 
 tion may be brought forward, namely, that the intraperitoneal 
 route of infection is unsatisfactory and cannot be depended upon 
 to give results. Experiments made by Knopf elmacher and by 
 Strauss and Huntoon can be explained in the same way; in these 
 instances also monkeys were infected with human virus, but the 
 attempt to inoculate further monkeys failed. 
 
 Personal Experiments with Monkeys. — The repeated failures 
 
ETIOLOGY OF THE DISEASE 33 
 
 to transmit the disease from ape to ape indicated that there was 
 some factor in the question which was as yet unknown. 
 
 When I began to perforin experiments myself, I had, of 
 course, Landsteiners experience before me; but I took advantage 
 also of Pasteur's work on " Hydrophobia." I have already drawn 
 attention to the analogy which exists between poliomyelitis and 
 rabies. Wickman had shown the close similarity of the histological 
 changes in the two diseases. My own researches had convinced 
 me that poliomyelitis was not caused by bacteria and that the 
 virus, like that of rabies, showed a selective preference for the 
 central nervous system. One of the first points in Pasteur's work 
 was the discovery of a practically certain method of transmitting 
 the disease from animal to animal. Anyone who knows the 
 history of his work knows what a definite advance was made 
 by the discovery of a new and certain technique for infecting the 
 animals. Pasteur used subdural or intracerebral injection of the 
 virus. I chose intracerebral injection into monkeys. 
 
 The technique is extremely simple. The monkey is enveloped in a 
 towel; an assistant holds the head; the head is shaved over an area the 
 size of a crown ; the operation is performed over the central gyri on one 
 side or the other, and in skilled hands does not require an anaesthetic. An 
 incision not more than 3 mm. long is made through the scalp down to the 
 bone ; the skull is perforated with a small bore in a few seconds ; a little 
 practice enables one to go through the skull without piercing the dura. 
 The needle of a small syringe filled with the virus is then passed into the 
 hole made by the bore, through the dura and into the brain to a depth of 
 about ii cm. ; not more than .5 to .6 c.cm. of the emulsion is injected slowly. 
 The needle is rapidly withdrawn, a small plug of gauze is pressed firmly 
 on the wound for a short time and the wound then closed with collodion. 
 The whole operation must be carried out with carefully sterilized instru- 
 ments. 
 
 By means of this intracerebral method I was able at once to 
 produce a disease in monkeys which was clinically and pathologically 
 identical with poliomyelitis in man; I was able also to transmit 
 the disease from one monkey to another. This proved t licit the 
 virus which caused the changes in the brain and spinal cord ZL'as 
 living and not merely a toxin. Considering that we and others 
 had proved that it was impossible to cultivate the virus on artificial 
 media, it was of the greatest importance that a means of cultivating 
 it in vivo had been discovered. In order that virus and disease 
 could be investigated experimentally, it was essential that some 
 method of cultivating the virus by means of transmission from 
 one animal to another should be available. 
 
 I reported my experiments in November, 1909, to the Medical 
 Society of Marburg and published them shortly afterwards in the 
 Munchcncr mcd. Wochenschrift. I believed at the time that I 
 was the first to succeed in transmitting the disease from one 
 animal to another. However, at the same time, and partly before 
 me, but all during the month of November, 1909, other results 
 
34 EPIDEMIC INFANTILE PARALYSIS 
 
 proving' the same point were published — Flexner and Lewis, on 
 November 13; Leiner and v. Wiesner, on November 18; and finally 
 Landsteiner and Levaditi, on November 27, 1909. 
 
 (a) SOURCE OF THE VIRUS USED IN MY EXPERIMENTS. 
 
 The original material was obtained from the brains and spinal 
 cords of patients who died from poliomyelitis during the epidemic 
 of the autumn of 1909 in Hesse-Nassau. To remove all doubt as 
 to the fact that the cause of death was poliomyelitis I append the 
 full clinical and post-mortem records of the cases. The clinical 
 notes were written by Professor Dr. Muller, the pathological 
 reports by Professor Dr. Beneke, who have kindly allowed me to 
 make use of them here. They have already appeared in a mono- 
 graph by Professor Muller. 
 
 I. — Julie M., aged 6 years, from Frankfort. History given by Dr. 
 Veupel in Frankfort. 
 
 The patient attended school up to the date of her illness. No other 
 source of infection known. On November 3 she became suddenly ill with 
 a high temperature (30/6 C), listlessness, anorexia, furred tongue, vomiting, 
 and constipation. She had pain in the neck, was restless at first, later 
 drowsy ; marked sweats, but no particular tenderness. She complained only 
 of pain in the neck and throat, and when she sat up she asked that her 
 head might be supported. No sphincter trouble. 
 
 When examined on the third day the child could not cry (there is no 
 record of other bulbar symptoms), arms normal, marked meteorism, flaccid 
 paralysis of both legs, deep reflexes absent. A short time before death she 
 rolled her eyes and was unable to cry or speak. Death occurred during the 
 evening. 
 
 Autopsy on November 6, 1909 : — 
 
 Development normal ; rigor mortis present ; moderate cyanosis ; marked 
 -post-mortem staining ; fat well developed ; muscles dry ; muscles of the 
 thigh soft and of a light grey-red colour; calf-muscles dry, dark red-grey 
 colour, firm. 
 
 Thorax. — A few drops of fluid in pericardium. Heart-muscle firm, 
 light grey-red colour, no marked degeneration. Lungs engorged ; no 
 pleurisy, no local lesions. 
 
 Trachea. — Markedly red along whole length; no exudate; marked 
 bronchitis, with much mucus in the larger branches. 
 
 Larynx. — Normal. 
 
 Tonsils. — On both sides double the normal size, not projecting, light- 
 grey in colour, covered with slight grey inflammatory exudate. 
 
 CEsophagus. — Nil. Thyroid. — Nil. 
 
 Abdomen. — Spleen slightly enlarged, soft, friable, dark red-grey > 
 follicles numerous. 
 
 Kidneys and suprarenals. — Nil, the former are slightly more red than 
 normal. 
 
 Genital organs. — Nil. 
 
 Liver. — Large, soft, dull, red-grey in colour, with many ischaemic 
 subcapsular areas. 
 
 Stomach. — Contains partially digested food and some mucus. Mucous 
 membrane rather dull, soft and red. 
 
ETIOLOGY OF THE DISEASE 35 
 
 Intestine. — Normal colour and contents ; the follicles in both small and 
 large intestine are increased in size; Peyer's patches are prominent and 
 certainly enlarged. 
 
 Cerebrospinal fluid obtained by lumbar puncture was copious, slightly 
 cloudy and colourless. A few drops of fluid in the ventricles of the brain. 
 
 Brain and spinal cord. — Moist, soft; the grey matter looks somewhat 
 red. No oedema of the pia ; no haemorrhages; no extradural oedema; no 
 gross local lesion in the anterior horns of the spinal cord grey matter. 
 
 Microscopical examination: — 
 
 (i) Dorsal spinal cord. — Moderate infiltration of the pia; vessels much 
 engorged. Marked infiltration of the ventral median fissure. Considerable 
 infiltration of anterior horns; posterior horns affected to a less degree. 
 Ganglion cells seen only in Clarke's column. In all sections the white 
 matter shows perivascular infiltration ; a similar condition found in the 
 cervical cord. In many places the limits of the infiltration mark off the 
 grey from the white matter in a very striking way. 
 
 (2) Medulla oblongata. — Slight infiltration of the pia ; marked peri- 
 vascular infiltration around the larger vessels; much scattered infiltration, 
 here and there clearly affecting the region of ganglion cells. Olives 
 practically unaffected. Marked enlargement of perivascular lymphatics. 
 
 (3) (a) Brain. — In the neighbourhood of the great ganglia some peri- 
 vascular infiltration ; here and there some subependymal infiltration, in 
 places almost forming abscesses, which is not connected with ganglion cells. 
 
 (b) Cortex. — Pia not affected; slight oedema of the vessel sheaths; no 
 infiltration. 
 
 Pathological diagnosis. — Poliomyelitis spin. cerebral; tonsillitis; 
 rhinitis post. ; tumour lien. ; hypertroph. follicul. intest. 
 
 From Professor Beneke I received portions of the pons and 
 of the lumbar cord; of each of these a piece the size of a pea 
 was emulsified in 8 c.cm. of the cerebrospinal fluid of the case. A 
 monkey weighing" 1,970 gm. (mangabey monkey, No. 1) was given 
 an intracerebral injection of this emulsion. The monkey died on the 
 eighth day after showing signs of paralysis (for details vide infra). 
 An emulsion of the spinal cord was injected into a second monkey 
 intracerebrally (mangabey, No. 2). This animal became ill on the 
 tenth day, and died on the eleventh. 
 
 The virus thus obtained will be called p.m. virus No. 6. 
 
 II. — Karl Schn., aged 2! years, from Marburg. No family history of 
 nervous disease. Parents and brothers and sisters remained well during 
 the patient's illness. The child had suffered from a club-foot, which had 
 been operated upon previously, and from furunculosis following vaccination 
 otherwise well. He attended an infant school where he came in contact 
 with children from the suburb Weidenhausen., which was an affected area. 
 A. few weeks ago the mother met a woman with her child who had suffered 
 from an attack of poliomyelitis some months previously. The father is a 
 shoemaker with an open shop, says that recently he has not worked for 
 families in which there was any poliomyelitis, that he has not had any 
 visits from or paid visits in any infected area. 
 
 The child became ill on November 22 with a high temperature and 
 rigor; much wandering and restlessness; sleepless, occasional jerking of 
 the limbs and starting up in bed. 
 
36 EPIDEMIC INFANTILE PARALYSIS 
 
 The mother reports that sweating was profuse. The child complained 
 that he " could not move " when he was lifted up, cried a great deal when 
 put on the chamber. On November 23 very little urine was passed, and the 
 child was unable to stand or walk alone, fell when he was put on his feet, 
 and " was quite slack like an idiot." 
 
 Examination on November 24. — Very pale, apathetic. Cranial nerves 
 not affected. Slight bronchitis, pulse-rate increased. The body is remark- 
 ably flaccid; the child cannot sit up; epigastric reflexes only just obtained. 
 Movements of the upper limbs are good; marked fine tremor of the hands 
 even when at rest. Child cannot stand or walk; falls down when put 
 on his feet. On the right side club-foot which has been operated upon. 
 Deep reflexes are still present on both sides; plantar reflex present. All 
 movement or touching of the legs causes pain. Leucopenia is present. 
 
 November 25. — High temperature (39' 5° C.). Great restlessness and 
 general collapse. Very pale; apathetic; alas nasi move with respiration; no 
 herpes; no membrane on the throat; no marked swelling of the glands of 
 the neck. Resonance diminished at the left base with bronchial breathing, 
 vocal resonance present; marked general bronchitis with dyspnoea, 
 although intercostals do not act and respiration seems to be entirely 
 diaphragmatic. Abdomen soft; some tympanites; abdominal reflexes 
 absent. The muscles of the limbs are generally hypotonic ; there is no 
 definite localized paralysis; the deep reflexes are present but diminished. 
 Lumbar puncture : copious clear sterile fluid, showing a few lymphocytes 
 on centrifugalization. Death occurred in the evening; the child was con- 
 scious, but unable to cry up to the last. 
 
 Autopsy on November 2g : — 
 
 Well-built child, aged 2I years ; pale ; moderate degree of club-foot ; 
 slight rickets; muscles soft. 
 
 Thorax (opened from behind). — Heart strong and not obviously degen- 
 erate. Upper lobe of left lung slight emphysema ; lower lobe grey-red in 
 colour, pneumonic ; bronchi contain some pus and mucus ; right lung normal. 
 
 Spleen normal in size, moist. Kidneys normal in size and shape, 
 microscopic examination normal. Blood taken from the left pulmonary 
 vein contains Diplococcus lanceolatus, but in addition a considerable number 
 of organisms of the nature of spirochsetes, staining feebly with Loffler and 
 showing feeble movements; some have granules like streptococci; also a few 
 grey oval bodies showing extremely active karyokinesis. The leucocytes 
 do not show karyokinesis ; it is confined to these large cells which, on the 
 other hand, contain no fat globules. Red blood-cells normal. In the 
 bronchial secretion exclusively Frankel's diplococcus was found. Blood 
 from spleen, heart and spinal cord contained no bodies like spirochaetes or 
 like the oval bodies described above. 
 
 The capillaries of the lung where it is not inflamed contain many 
 polymorphonuclear leucocytes. In the inflamed parts there is rather an 
 absence of leucocytes. In the larger arteries and veins of the lungs the 
 blood contains mainly lymphocytes, leucocytes being rare. The pneumonic 
 infiltration contains many leucocytes, the exudate being serous rather than 
 suppurative. 
 
 Heart. — The musculature shows no abnormality ; there is no infiltration. 
 
 Spleen. — Follicles markedly enlarged; the central portion is large with 
 many degenerate nuclei ; the periphery is comparatively free from degenera- 
 tion. Many follicles are composed almost completely of germinal areas 
 with practically no peripheral portion. Spleen pulp hyperaemic, generallv 
 disintegrated and poor in cells. 
 
ETIOLOGY OF THE DISEASE 37 
 
 Kidneys. — Slight signs of irritation in the convoluted tubules ; no other 
 pathological appearances. 
 
 The dura contains a small amount of fluid. Spinal cord firm, white 
 matter normal, grey matter everywhere red. 
 
 Dorsal region of the cord. — Slight infiltration of the pia ; infiltration 
 more marked around the vessels in the anterior longitudinal bundle, most 
 marked in the vessels of the anterior horns and in the anterior portion 
 of the lateral tracts. Central canal normal. Diffuse infiltration of both 
 anterior horns, they are small and show only traces of the ganglion cells. 
 Definite oedema. Clarke's column quite unaffected, ganglion cells normal. 
 In the white matter some local lesions. Ganglion cells are found practically 
 not at all throughout the anterior horns. Occasionally a normal ganglion 
 cell is seen. 
 
 Pathological diagnosis. — Poliomyelitis acuta; pneum. lob. inf. pulm. 
 sin. ; bronchitis purulenta. 
 
 From the lumbar cord a 5 per cent, emulsion was made in 
 normal saline and injected on the same day into the brain of a 
 Macacus rhesus (No. 4). The amount used was '3 c.cm. The 
 monkey remained well ; on December 2 and 3 it seemed to us that he 
 did not care about using" his right fore limb, but this weakness 
 gradually disappeared. It is possible that this was one of the 
 abortive cases which are seen in man frequently. 
 
 Thus it was not possible to transmit the disease from this case 
 of undoubted poliomyelitis to a monkey in a manner which was 
 devoid of doubt. The question whether we should have succeeded 
 if we had used more monkeys cannot be discussed. The fault did 
 not lie with the animal (No. 4), because at a later date, and with a 
 different virus, it died rapidly with paralysis. One point may be 
 mentioned : that the lumbar cord was not examined microscopically 
 as the dorsal cord had been. 
 
 III. — Karl D., aged 2! years, from Arfurt. Report from Dr. Hartmann, 
 of Villmar a. d. Lahn. Nothing known of method of infection. No illness 
 in the family or neighbourhood ; no mortality among animals. The family 
 had not left their premises during the last few weeks, nor had they had 
 visitors. The nearest place where cases of poliomyelitis have occurred 
 recently is two kilometres distant. 
 
 The child became ill on November 29. Fever, lassitude, one attack 
 of vomiting. Cough and restlessness ; no sweats or hyperesthesia. On the 
 fourth day palsy of the neck and left arm; no affection of the bulb or 
 cranial nerves. On the next day the right arm and leg were attacked. The 
 muscles of both legs were flaccid and the deep reflexes absent. Death on 
 the sixth day (December 2). 
 
 Autopsy on December 4, 1909 : — ■ 
 
 Well-developed child; cyanosis slight; fat well developed; muscles soft, 
 rather pale. 
 
 Heart and lungs. — Normal. 
 
 Spleen very large, tense, dark black red in colour, firm and dry. 
 
 Kidneys and liver dull, engorged, otherwise normal. 
 
 Intestines. — Marked hypertrophy of the follicles. 
 
 Mucous membrane of the stomach smooth, fairly thick, very red, 
 covered with thick layer of pus and mucus. 
 
38 EPIDEMIC INFANTILE PARALYSIS 
 
 Organs of the throat normal. 
 
 Tonsils and glands in the neck small, pale. 
 
 Pancreas. — Normal. 
 
 Peridural fat normal. Spinal cord soft. Sections show definite red dis- 
 coloration of the grey matter, which is shrunk and softened. White matter 
 is bulky and moist. 
 
 Dura is tense. Pia not cedematous, markedly red, the whole brain is 
 of a diffuse red colour. 
 
 Microscopical examination : — 
 
 (1) Dorsal region. — No infiltration of the pia. Little infiltration in the 
 anterior longitudinal fissure; rather more in the anterior horns and adjacent 
 white matter. Central canal in places infiltrated with small round cells; 
 anterior horns small, cells almost absent; a diffuse patchy infiltration with 
 mononuclear and polymorphonuclear cells. Clarke's column unaffected; 
 no other infiltration. 
 
 (2) Cervical region. — Widespread, well-marked infiltration of the 
 anterior horns; in places a few ganglion cells remain. Moderate hyperaemia, 
 slight oedema, marked infiltration of the vessel sheaths. In the rest of the 
 cord only a slight diffuse cell infiltration. 
 
 (3) Medulla oblongata. — Ependyma raised slightly by oedema; marked 
 perivascular infiltration in the subependymal region and round the larger 
 vessels. A diffuse fairly well-marked cell infiltration not directly related 
 to any particular cell group. Olives and ventral part of sections unaffected. 
 
 (4) Pons. — Slight infiltration round larger vessels; a few local lesions 
 found in pons and in cerebellar peduncles. Cerebellar convolutions normal. 
 The large cell nuclei of the pons are remarkably free from disease, which 
 is most marked around the aqueduct and the larger vessels in this region. 
 Ventral portion unaffected. 
 
 (5) Thalamic region. — Marked linear infiltration round the vessels. 
 Ganglion cells in the neighbourhood of the infiltration are destroyed; other 
 areas of ganglion cells unaffected. 
 
 (6) Cerebral cortex. — Only a few scattered cells in the pia; perivascular 
 lymph spaces much enlarged ; no definite infiltration. 
 
 (7) Hippocampus. — Relatively large, in places marked, vascular in- 
 filtration, also general diffuse infiltration. 
 
 Pathological diagnosis. — Poliomyelitis acuta; enlargement of the 
 spleen ; acute gastritis ; renal and hepatic degeneration. 
 
 A 5 per cent, emulsion was made from the lumbar cord and 
 injected as follows: — 
 
 The monkey No. 8 (Cercopithecus ruber) received an intra- 
 cerebral injection of '4 c.cm. ; it remained well until December 15, 
 1909; on the 16th it became weak in the hind-limbs, there was 
 tremor of the head, and the monkey was depressed. On the 17th 
 general condition improved, but the paresis of the hind-limbs was 
 more marked. The paresis began to improve on the 18th and 
 disappeared by the 21st (? abortive poliomyehtis). 
 
 Monkey No. 9 (Cercopithecus fuliginosus) was given 1 c.cm. 
 subcutaneously, and remained healthy. It was observed until 
 February 15, 1910. 
 
 Monkey No. 10 (Cercopithecus fuliginosus) had '2 c.cm. injected 
 direct into the left sciatic nerve, and remained entirely healthy up 
 to January 15, 1910. 
 
ETIOLOGY OF THE DISEASE 39 
 
 Monkey No. 6 (Macacus rhesus) received - 8 c.c. of a 2-5 per 
 cent. solution which had passed through a Berkefeld filter, injected 
 into the brain. It remained quite well (observed until January 5, 
 1910). 
 
 No success therefore attended the attempts to transfer the 
 disease to monkeys by means of the virus of Case III. 
 
 IV. — Wilhelm P., of Weifenbach, near Biedenkopf, aged q months. 
 Admitted to hospital on December 6, 1909. The first case of the disease 
 in that village. Parents and three brothers and sisters quite well both 
 before and during patient's illness. On November 27 the child had a boil 
 on the neck, which disappeared without medical treatment. The child is 
 still being suckled and has had no illness. The father is a telegraph 
 official, and has to go about all over the district. No other possible source 
 of infection is known. 
 
 Onset of the disease occurred on December 2 ; high fever, vomiting, 
 anorexia, somnolent during the day and wakeful at night. Diarrhoea. On 
 the following night convulsions, the eyes being rolled and the face drawn 
 to the right side. No stiffness of the neck. General tenderness : the child 
 objects when it is touched, though it is unable to cry. Marked sweating, 
 particularly of the head. Incontinence of urine. 
 
 Examination on December 5. — Eyes normal; mouth drawn over to the 
 right ; swallowing difficult ; bronchitis ; other organs normal ; abdomen soft ; 
 abdominal reflexes absent ; cremasteric reflexes absent. 
 
 Hypotonia of all extremities; both arms and legs paralysed. Deep 
 reflexes all absent. 
 
 Lumbar puncture. — 12 c.c. of clear, sterile fluid under considerable 
 pressure. Centrifugalized showed a few lymphocytes. 
 
 December 6. — No improvement ; passing much mucus ; much dyspnoea ; 
 during the night suffocative attacks requiring artificial respiration. 
 
 December 7. — Pulse fair ; respiration diaphragmatic. Heart improved 
 after a second lumbar puncture. During the evening collapse aiid death 
 from respiratory failure. 
 
 Autopsy on December 7. 
 
 Well-developed child ; marked -post-mortem staining. Rigor mortis 
 fairly well marked; scars of punctures in the back. Muscles of the bad: 
 dry and soft. 
 
 Extradural connective tissue oedematous. 
 
 Abdominal organs normal. 
 
 Spleen small, rather shrivelled, but full of blood. Thymus large ; clear 
 fluid in pericardium; heart full of clots, firm and dark-red musculature. 
 No demonstrable degeneration. Left lung very hyperaemic, more so in 
 lower lobe, soft, contains air. Some mucus in bronchi ; mucous membrane 
 pale. Right lung almost entirely collapsed ; bronchi do not contain much 
 mucus ; the mucous membrane is pale. 
 
 Parotid gland normal. Glands in neck normal. Tonsils small ; no 
 sign of inflammation ; base of tongue and mouth the same. 
 
 Larynx and trachea normal. Thyroid normal. Upper portion of 
 pharynx somewhat swollen; nasal mucous membrane slightly red and 
 covered with pus. Inferior turbinate much swollen with mucopurulent 
 catarrh above. The upper portion of the nasal cavity, together with the 
 septum, show only slight redness of the mucous membrane. 
 
 Intestines are distended with gas; in the lower part a ■post-mortem 
 
40 EPIDEMIC INFANTILE PARALYSIS 
 
 invagination. Lymph nodules remarkably enlarged, containing many 
 malformed nuclei. The larger lymphatics in many places distended with 
 lymphocytes. 
 
 Appendix. — Shows condition similar to that of ileum; much lymphoid 
 tissue; lymphatics distended with lymphocytes; many wander cells in the 
 lymph nodules. 
 
 Adrenals are small and pale; kidneys deep red-grey in colour, full of 
 blood, no obvious degeneration. 
 
 Liver small; on section rather dull and dry; microscopical interstitial 
 infiltration ; some apparent increase in wander cells, which here also tend 
 to form rows of cells ; no abscess formation. 
 
 Microscopical examination : — ■ 
 
 Lymphatic glands. — Germ centres much developed, with extraordinary 
 number of malformed and degenerate nuclei of wander cells. Lymph 
 channels packed with lymphocytes. 
 
 Thymus. — Hypersemic, but not otherwise abnormal. 
 
 Spleen. — The germ centres of the follicles are large, and contain many 
 malformed nuclei. Many follicles contain only germ centres. Pulp 
 relatively poor in cells. 
 
 Testis. — Normal; no infiltration. Epididymis the same. Blood-vessels 
 normal. 
 
 Bone-marrow (from vertebras). — Structure very dense, full of cells; 
 hypertrophied. Fairly numerous leucocytes; a few giant cells. 
 
 The middle part of the spinal cord removed for bacteriological pur- 
 poses. The rest shows marked redness and softness of the grey matter, the 
 white matter being of a relatively firm consistency. Considerable subdural 
 haemorrhages in the form of flat, soft coagula. Pia very hypersemic in the 
 region of the right anterior vein. The ventricles appear empty. (Edema 
 of the extradural connective tissue. The brain firm and moist. Cerebral 
 cortex rose-coloured ; marked venous hyperasmia in cortex, white matter 
 and large ganglia ; no oedema of the pia. The base of the brain, particu- 
 larly the medulla, is very red. Sections through the pons and cerebellar 
 peduncles show moderate hyperaemia. Consistency of the medulla prac- 
 tically normal ; the colour of the grey matter is normal. 
 
 Cerebrum. — In the region of the uncinate gyrus, both in the cortex and 
 the white matter, many separate wander cells of various shapes. The pial 
 vessels are filled in places with leucocytes, which almost constitute a 
 thrombus. Xo abscess. 
 
 Convexity. — Moderate infiltration of the pia ; slight oedema of the 
 perivascular lymph spaces; everywhere degenerate wander cell nuclei; no 
 well-defined lesion or marked infiltration. 
 
 Pes hippocampi. — Everywhere wander cells and small infiltrations, 
 chiefly subependymal; vessels hypersemic; many leucocytes sometimes 
 causing a thrombus; a similar condition in a few instances in the veins of 
 the choroid plexus. 
 
 Microscopical examination of the cord and brain stem : — 
 
 Lumbar region. — Marked infiltration of the vessel sheaths. Consider- 
 able cell infiltration in the anterior longitudinal 'fissure. Anterior horns 
 on both sides show great infiltration and oedema of the vessel sheaths, with 
 wander cells of various shapes. A few ganglion cells are present; these do 
 not appear changed. In the rest of the section only a slight perivascular 
 infiltration. Nerve roots normal. 
 
 Dorsal region. — Infiltration is less in degree, but similar in dis- 
 tribution. Anterior horn cells are in many cases atrophic, but are not 
 invaded by leucocytes. 
 
ETIOLOGY OF THE DISEASE 41 
 
 Cervical region. — Similar to lumbar region. Hypersemia well marked; 
 much oedema and infiltration of the anterior horns. The wander cells have 
 nuclei of a remarkably long, thread-like shape. 
 
 Medulla oblongata. — Much perivascular infiltration in the region of 
 the ependyma ; also some diffuse infiltration in that region. A few wander 
 cells present all over the section, also in the olives, of an elongated shape 
 and fairly numerous. 
 
 Pons. — Considerable pial infiltration at the base where the vessels con- 
 tain a large number of leucocytes. A fair number of long-shaped wander 
 cells. Xear the aqueduct both infiltrations and wander cells are more 
 numerous; the infiltration is in the form of local collections of cells, the 
 ganglion cells in the neighbourhood being quite well preserved. 
 
 Pathological diagnosis. — Acute poliomyelitis; collapse of the lung; 
 follicular catarrh of the intestines. 
 
 Five per cent, emulsions were made from the lumbar cord, the 
 dorsal cord and the brain in the region of the basal ganglia. They 
 were used for inoculation in the following manner: — 
 
 Monkeys (tf) and (b) (both Ccrcopithccus fuliginosus) received 
 an intracerebral injection of '5 c.c. on December 7, 1909. Monkey 
 (a) became ill on the 14th and died on the 15th. Monkey (b) 
 sickened on the 15th and died, typically paralysed, on the 16th. 
 
 '5 c.c. of a 1 in 10 dilution of the original emulsion was injected 
 intracerebrally into monkey Xo. 11 (Macacus rhesus). Paralysis 
 set in on December 20, 1909, and death occurred on January 11, 
 1910. 
 
 The virus obtained from Case IV is referred to as virus Xo. 11, 
 and was made the basis of many further injections into monkeys. 
 
 V. — Heinrich R., aged 3, from Schweinsberg. Parents and other 
 children well both before and during illness of patient. Child at school 
 up to date of illness. Xo other possible source of infection known. 
 
 December 11. — Fever, headache, anorexia, vomiting. Sleep restless, 
 much crying out and tossing in bed. Head retracted; spine held stiff. 
 When taken hold of child complained much of pain. Xo respiratory or 
 intestinal trouble ; no sweats. 
 
 December 12. — Examination at the medical clinic. Remarkable dermo- 
 graphia over the whole body. Eyes and cranial nerves normal. Difficulty 
 in swallowing ; mouth clear. Head and spine held rigid ; abdomen soft. 
 Possibly some paresis of the right shoulder muscles; left upper and both 
 lower limbs normal. Deep reflexes and plantar reflexes present. Kernig's 
 sign positive. 
 
 December 13. — Much headache; rigidity of head and spine more 
 marked. At noon, sudden attack of dyspnoea, with failure of pulse and 
 cyanosis. The head fell limply to the right side. Towards evening tracheal 
 rales. Paralysis of muscles of respiration. X-ray examination showed that 
 only the left half of the diaphragm was still acting. Oxygen improved 
 the pulse. Later respiration became more embarrassed. Deep reflexes 
 abolished in all limbs. Epigastric reflexes present. Death from respiratory 
 paralysis. Lumbar puncture and brain puncture had proved useless. 
 
 December 14. — Autopsy. 
 
 "Well-developed child; fat abundant; muscles well-developed; skin pale. 
 
 Xo degeneration in the muscles. 
 
42 EPIDEMIC INFANTILE PARALYSIS 
 
 Lungs.— Pleura clear. Many large areas of collapse in both lungs. 
 Much frothy, yellow-brown mucus in the bronchi. Very slight redness of 
 mucous membrane. Pharynx, larynx, and trachea normal. Spleen 
 moderate in size, tense, firm, dark red. Liver small, soft, contains fair 
 amount of blood, rather dull. Adrenals small, elongated, and soft. Kidneys 
 engorged, otherwise normal. Stomach contains much thick yellow-brown 
 mucus, with many black thread-like clots. Many small haemorrhages in 
 the mucosa, which is red. All lymphatic tissue in the intestinal tract is 
 swollen; mucous membrane red in places. Pancreas and urogenital tract 
 normal. The spinal cord was removed whole. 
 
 On section the grey matter was distinctly more red than normal. The 
 white matter moist and swollen. Over the brain the dura was tense. Over 
 the right parietal region a superficial haemorrhage about the size of a five- 
 shilling piece. The whole brain engorged; the white matter universally 
 rose-coloured. Ventricles empty; not enlarged. The pons definitely 
 hyperaemic. 
 
 Microscopical examination : — 
 
 Medulla. — Slight, definite perivascular infiltration of the subependymal 
 vessels. In the substance of the medulla many disseminated infiltrations 
 with elongated and degenerate cell nuclei. Some of these infiltrations are 
 of considerable size. 
 
 Ganglion cells which are implicated in these infiltrations show 
 degeneration, and are attacked by leucocytes. In the region of the olives, 
 and generally in the deepest parts of the sections, no infiltration. 
 
 Pons. — The basal pia shows cell proliferation ; no perivascular infil- 
 tration in the pia, but much in the region of the iter and fourth ventricle, 
 both perivascular and diffuse. Wander cells are few except in the infiltrated 
 parts. 
 
 Cerebellum. — Pia almost unaffected ; here and there small infiltrations ; 
 cortex and medulla free of inflammation. 
 
 Ganglia of mid-brain. — Some slight subependymal cedema ; some 
 indications of perivascular infiltration ; in places a suggestion of local 
 infiltration. 
 
 Spleen. — Well-developed follicles with large germ centres. In these 
 markedly malformed, elongated, and degenerate nuclei, but no definite 
 necrosis. Here and there slight hyaline degeneration. 
 
 Pathological diagnosis. — Acute poliomyelitis ; collapsed lung ; acute 
 gastritis; follicular catarrh of the intestines. 
 
 A 20 per cent, emulsion was made from about equal portions 
 of the brain stem, the medulla oblongata, and the dorsal region of 
 the cord. Monkeys Nos. 13 and 14 received '5 c.c. intracerebrally, 
 and at the same time 3 c.c. into the peritoneum. Xo. 13 became 
 paralysed on December 26, and died on January 5; Xo. 4 was para- 
 lysed by December 23, and died on December 24. On histological 
 examination typical poliomyelitis was found in both cases. The 
 virus obtained from Case V will be called .Virus Xo. 12; it was 
 passed through many animals. 
 
 The Susceptibility of Monkeys to the Virus of Poliomyelitis..— 
 We succeeded in transmitting the disease to monkeys in three out of 
 five human cases ; we were able to transmit the disease to other mon- 
 keys in these cases. In two cases the disease could not be transmitted. 
 I can give no satisfactory reason why this was the case. I consider 
 
ETIOLOGY OF THE DISEASE 43 
 
 that the possibility has not been excluded, that the parts of the cord 
 selected were affected but slightly by the disease, and consequently 
 contained only a small amount of virus. One result of the experi- 
 ments is that in any single case of poliomyelitis it is advisable to 
 inoculate several monkeys either intracerebrally only or together 
 with an intraperitoneal injection. It is not justifiable to draw the 
 conclusion that it is possible to infect only three-fifths of all 
 monkeys. For such a purpose a much larger number of animals 
 would have to be used. In that case I believe that a much larger 
 percentage of animals would be found to be susceptible to the 
 disease, considering that at the time we made our experiments our 
 knowledge of the technique of inoculation was in its infancy. At 
 the same time Leiner and v. Wiesner have reported lately that out 
 of six cases they were able to infect monkeys in only three. 
 
 The figures of re-inoculation from monkey to monkey are quite 
 different. Taking all the experiments together, in which sufficient 
 doses of virus were given to unaffected monkeys by cerebral injec- 
 tion, the results are as follows : Out of forty-two monkeys thirty- 
 eight became paralysed, of which the greater number died: in two 
 animals the symptoms were doubtful, and two remained quite well. 
 If the doubtful cases are added to those which remained well the 
 resulting figure is 9.8 per cent, of failures; in 90.2 per cent, there- 
 fore, infection followed at once. I may mention that in the cases 
 in which the virus was injected into both brain and peritoneum, 
 the number of successes was 100 per cent. My figures correspond 
 very closely with those obtained by Flexner and Lewis : Eighty- 
 three monkeys received an intracerebral inoculation; of these 
 seventy-seven became markedly paralysed, two slightly paralysed, 
 while four remained well, i.e., 95 per cent, of successes. Landsteiner 
 and Levaditi had 95 per cent., Leiner and v. Wiesner 85 per cent, 
 of positive results. The latter authors found intraneural injection 
 to be as successful as intracerebral. 
 
 I used Cercopithecus fuliginosus, C. ruber. Macacus rhesus, 
 M. cynomolgus. and in one instance a Tota monkey. Flexner 
 and Lewis found that M. nemestrinus, C. callitrichus, and Papio 
 babinm were susceptible; Landsteiner and Levaditi the chimpanzee, 
 M. sinicus, and the mandrill. Flexner and Lewis found that the 
 monkeys of the Xew World were not so susceptible as those of the 
 Old. It is of interest to note that phylogenetically the monkeys 
 of the Xew World are less closely related to man. Liener and 
 v. Vviesner found that young monkeys were more susceptible to 
 the disease than old ones. 
 
 (b) THE CLINICAL HISTORY OF POLIOMYELITIS IN 
 
 MONKEYS. 
 
 Period of Incubation. — I have personal experience only of cases 
 which were caused by intracerebral inoculation or simultaneous 
 intracerebral and intraperitoneal inoculation. The duration of the 
 incubation period varied from three and a half days to fifteen days, 
 
44 EPIDEMIC INFANTILE PARALYSIS 
 
 an average of nine and a half days. Other authors record a similar 
 average figure. The shortest period observed by Landsteiner and 
 Levaditi was four days, the longest twenty. Flexner and Lewis 
 state that out of eighty-one monkeys eighteen were paralysed before 
 the eighth day, and sixteen after the twelfth day; the longest period 
 which they observed was thirty-three days; the majority of the ani- 
 mals became ill between the eighth and twelfth days. Leiner and 
 v. YVeisner even record a period of forty-six days in one case, in 
 which the virus had been passed through a Riechel filter. 
 
 The amount of virus used seems to have some effect upon the 
 length of the incubation period. All the above writers report that 
 whenever the virus was passed though a filter capable of holding 
 back all bacteria the incubation period was longer. It is probable 
 that the filter keeps back some of the virus, and that, in effect, a 
 smaller dose of virus is administered. Leiner and v. YYiesner report 
 a case in which the spinal cord emulsion was first centrifugalized, then 
 repeatedly passed through filters of paper and wadding; the period of 
 incubation with the filtered virus was twenty-seven days, while in a 
 control in which unfiltered virus was used the period as only seven 
 days. Flexner and Lewis have observed that when the virus is 
 administered by any other way than by intracerebral injection (e.g. f 
 subcutaneously or into the peritoneum) the period is longer; like- 
 wise when other organs than the brain and spinal cord are used for 
 making the emulsion. Leiner and v. Wiesner record an incubation 
 period of twenty-three days in a monkey which had been given the 
 virus by mouth. I myself gave intracerebral injections of the con- 
 centrated emulsion to two monkeys, one-tenth of the dose to a 
 third, and one-hundredth of the dose to a fourth: the first two 
 became ill on the seventh day and died on the eighth, the third 
 sickened on the twelfth and died on the thirtieth day. while the 
 fourth monkey remained well. Leiner and v. Wiesner showed that 
 it is true only up to a certain point that an increased dose shortens 
 the period of incubation and increases the severity of the attack: 
 when a certain point had been reached they found that increasing 
 the dose made the incubation longer and the attack less severe. 
 They believe that the central nervous system contains a substance 
 antagonistic to the virus (as is known to be the case in rabies), 
 although they have not succeeded in demonstrating its presence in 
 monkeys. 
 
 Prodromal Symptoms. — Sometimes, but not constantly, certain 
 indefinite S)-mptoms precede the paralysis. The monkeys are less 
 merry; they are tired, do not climb about so much; their expression 
 becomes discontented and surly; sometimes they seem to age, their 
 eyes become dull. Occasionally there is a tremor of the whole 
 body, particularly of the head. Fairly frequently gastro-intestinal 
 symptoms appear, anorexia, diarrhoea, and sometimes vomiting. I 
 have observed, however, that the gastro-intestinal symptoms occur 
 more commonly later when paralysis is beginning. The temperature 
 did not show any characteristic changes; in most cases our animals 
 
ETIOLOGY OF THE DISEASE 
 
 45 
 
 were wild, and the chase necessary to capture them caused a con- 
 siderable rise in temperature. In the case of three tame animals a 
 reliable record could be obtained; all these suffered from typical 
 poliomyelitis ending in death, and I give the temperature charts in 
 figs. 6 to 8. Monkey Xo. 4 shows a considerable rise of tempera- 
 ture two days before any paralysis was apparent; on the first day 
 of paralysis the temperature remained raised, and only became 
 subnormal on the second day shortly before death. In monkeys 
 Nos. 13 and 14 the temperature was apparently not affected by the 
 disease. The shaded areas in the figures represent the degree of 
 paralysis. Leiner and v. Wiesner, also Flexner and Lewis, could 
 
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 Fig. 7. 
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 not find any typical change in temperature during the prodromal 
 sta°"e. 
 
 Vtage Of Paralysis..— This stage frequently begins suddenly 
 without any warning symptoms. Monkeys which in the evening 
 were seen to be quite lively were found paralysed in one or more 
 limbs on the following morning; even during the day in the course of 
 a single hour a monkey became severely paralysed. The clinical 
 course varied very much in different animals. The several types of 
 paralysis, together with the examples on which they are based, will 
 be described below. Of great interest and importance from the point 
 of view of the pathogenesis of the disease is the fact that, although 
 
46 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 the monkeys were infected in the brain, the paralysis is in almost 
 all cases of the spinal type, flaccid and with consequent atrophy, 
 while the paralysis affects the limbs first of all; further, the lower 
 limbs are affected more often and more severely than the upper. 
 The type of paralysis which is most common in man is most common 
 in monkeys. There is therefore a close analogy between the disease 
 artificially produced in monkeys and that occurring naturally in 
 man, although the point of entrance of the virus is undoubtedly 
 different in the two cases. 
 
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 Fig 8. 
 Monkey No. 14. 
 
 (a) Poliomyelitis acutiSSima.— After intracerebral infection the 
 course of the disease may be so rapid that one can hardly speak of 
 a paralytic stage. The following are two such cases: — 
 
 Monkey No. 45 {Macacits rhesus) was injected on Apiil 7, 19 10, with 
 "5 c.c. of emulsion of virus No. 6, and at the same time with 4 c.c. of the 
 same intraperitoneally. 
 
 At 10 o'clock on the evening of the 13th eyes dim; climbs about in a 
 tired way, but with complete control of all limbs. 
 
 At 7 a.m. on the 14th found dead in the cage. 
 
 On histological examination, typical changes in cord and medulla. 
 
 Monkey No. 1 [Cercofithecus fuliginosus), intracerebral injection with 
 '5 c.c. of virus No. 6 on September 6, igog. 
 September 7-12. — No change. 
 September 13. — Languid and sad; no paresis visible. At n p m. I 
 
ETIOLOGY OF THE DISEASE 47 
 
 happened to be at the laboratory, and observed a slight paresis of the left 
 fore limb; the animal still used the limb, but it gave way under him, and 
 there was less resistance to passive movements. The tone of the muscles 
 appeared diminished. 
 
 September 14. — The monkey lies on the floor apparently completely 
 paralysed in all limbs. The mind is clear; with the eyes he follows move- 
 ments of objects. The neck muscles appear unaffected. On trying to place 
 him on his feet he collapses at once. Death occurred in the evening. The 
 -post mortem revealed very typical poliomyelitis. 
 
 In both these animals (Nos. 45 and 1) the form of the disease 
 was so acute and atypical that it would have been difficult to be 
 certain that death was due to infection with poliomyelitis if it were 
 not for the microscopical examination and the results of inoculating 
 the virus into fresh animals. In the most severe cases, where all 
 four limbs are affected together and suddenly, it is difficult to 
 determine whether the animal is suffering merely from extreme 
 general weakness due to a severe infectious disease or from an 
 actual paralysis due to a lesion in the spinal cord. Leiner and 
 v. Wiesner also record a case in which death occurred without any 
 preliminary paralysis on the sixth day after infection; in this case 
 the cause of death was proved to be true poliomyelitis by means of 
 microscopical examination. Flexner and Lewis also report a case 
 of experimental poliomyelitis in a monkey in which death occurred 
 a few hours after the onset of paralysis. Such cases remind one 
 of Landry's disease in man; Wickman finds that the great majority 
 of cases of Landry's disease are merely examples of a particular 
 type of Heine-Medin disease. 
 
 (b) Poliomyelitis acuta. — In other cases death does not occur 
 so rapidly, but still more quickly than in the majority of human 
 cases. An example is the following: — 
 
 Monkey Xo. 2 [Cercofithecits fuligiiiosus). — On November 17, 1909, 
 received an intracerebral injection of '4 c.c. of an emulsion made from 
 virus No. 6. 
 
 November 17-26. — Remained well. 
 
 November 27. — Depressed; remains huddled on the floor of his cage. 
 No apparent paralysis. 
 
 November 28. — Marked flaccid palsy of both hind limbs ; moderate degree 
 of flaccid palsy of fore limbs ; the hind limbs can still be moved with the 
 help of the fore limbs ; movements of the tail still powerful ; the muscles 
 of the back seem to be affected. No cranial nerve lesions. Death during 
 the night of November 28. 
 
 The histological findings were very typical. 
 
 (c) Typical Spinal Paralysis. — Other cases are quite comparable 
 to those in man. which develop gradually, show wide spread of the 
 paralysis, and end in death within a few days. Examples are: — 
 
 Monkey No. 29 {Macacas rhesus) received an intracerebral injection on 
 February 7, 1910, '35 c.c. of virus No. 12, filtered through paper and mixed 
 with '35 c.c. of the serum of a healthy monkey. 
 
48 EPIDEMIC INFANTILE PARALYSIS 
 
 February 8-14. — Remained well. 
 
 February 15. — When walking in the evening spares the right hind limb. 
 
 February 16. — Both hind limbs almost entirely paralysed; upper limbs 
 appear quite unaffected. The monkey moves forwards by means of the 
 arms and drags the flaccid hind limbs. 
 
 February 17. — Total flaccid palsy of the hind limbs. 
 
 February 18, a.m., in statu quo ante; p.m., the resistance of the right 
 fore limb is less on passive movement; the limb frequently gives way under 
 the animal. Much diarrhoea. 
 
 February iq. — Condition unchanged. 
 
 February 20. — In statu quo. Diarrhoea has ceased. 
 
 February 21. — The fore limbs are now completely paralysed; the 
 monkey lies quite flaccid on the ground ; apparently the muscles of the neck 
 are paralysed, as the chin also lies on the ground; there is no resistance to 
 passive movement of the head, and it drops on to the ground when one lets 
 go of it. Xo lesion of the cerebral nerves. 
 
 February 22. — Death. 
 
 Histological examination shows typical poliomyelitis, mainly in the 
 lumbar cord and the medulla. 
 
 FIG. 9. 
 Monkey No. 14. 
 
 Monkey Xo. 14 [Macacus rhesus), intracerebral injection of '5 c.c. of 
 virus Xo. 11 emulsion on December 17, iqoq. 
 
 December 18-25. — Xo signs of illness. 
 
 December 26. — Slight weakness of the hind limbs, which often give way 
 under the animal and cause it to fall to one side. Otherwise they can be 
 nsed quite well. The resistance of the hind limbs seems less than normal. 
 
 December 27. — Almost total flaccid palsy of the hind limbs. 
 
 December 28. — Fore limbs now markedly paralysed. Resistance to pas- 
 sive movements still quite good in the fore limbs. 
 
 December 2Q. — Total flaccid palsy of all limbs. Cranial nerves not 
 affected ; compare the photograph above, which was taken on this day. 
 
 December 30. — Death at 2 p.m. 
 
 Microscopic appearances in the cord are typical. 
 
 Monkey Xo. 46 {Macacus rhesus), intracerebral injection of '5 c.c. and 
 intraperitoneal injection of 4 c.c. of an emulsion of virus Xo. 11 on April 7, 
 1910. 
 
ETIOLOGY OF THE DISEASE 49 
 
 April 8-16. — Xo apparent disturbance. 
 
 April 17. — Marked flaccid pals}- of the right hind limb. Much diarrhoea. 
 In the afternoon total paralysis of the right and possibly a slight palsy of 
 the left hind limb. 
 
 April 18. — In the morning total paralysis of both hind limbs. The 
 monkey can move only by means of the fore limbs. On attempting to climb 
 he pulls himself up by his fore limbs, but is unable to use his hind limbs. 
 In the evening found crouching on the floor of his cage. Marked palsy 
 of the right upper limb. Can no longer climb at all ; the animal cannot 
 even climb over the threshold of the cage, which is only 15 cm. high. He 
 can still seize and grasp an apple with the left hand. 
 
 April ig. — Condition in statu quo. Slight palsy of left arm. 
 
 April 20. — Total flaccid palsy of all extremities. 
 
 April 21. — Moribund. Death during the afternoon. 
 
 Histological examination. — Very typical changes of poliomyelitis in 
 the spinal cord. 
 
 (d) Bulbar and Cerebral Forms. — The preceding types are the 
 most common in monkeys; they are spinal only in so far as clinical 
 observation is concerned, as the microscopical appearances always 
 show more widespread disease than one would expect from the 
 clinical signs. In most of my cases the paralysis was of the ascend- 
 ing type, beginning in the leg's, next attacking the arms, and finally 
 causing" death by involvement of the medulla. I lay particular 
 stress on this point because the path of infection was in all cases by 
 the brain and in most cases exclusively. I shall return to this later. 
 Occasionally the cerebral nerves were affected, and in most of such 
 cases it was possible to demonstrate that the nerve nuclei were 
 affected by the disease. These cases constitute therefore a bulbar 
 type quite similar to that observed in man. 
 
 Monkey Xo. 48 [Macacus rhesus), on April 7, iqio, received an intra- 
 cerebral injection of '5 c.c. and an intraperitoneal injection of 4 c.c. of an 
 emulsion of virus X"o. 11. 
 
 April 8-16. — Xo signs of disease. 
 
 April 17. — Slight palsy of the left fore limb and the right hind limb 
 just perceptible. AVhen climbing about his cage the monkey falls frequently. 
 In the afternoon the left arm quite paralysed; the palsy of the right leg 
 more marked. 
 
 April 18. — Besides the paralysis of the left arm there is some paralysis 
 of both hind limbs. In the evening weakness of the right arm. The animal 
 falls to one side while walking. 
 
 April ig. — The monkey sits crouching on the floor of the cage. Total 
 palsy of the left arm, definite weakness of the right arm. The animal is 
 still able to hold a small apple in the right hand for some minutes. Marked 
 palsy of both hind limbs. AVhile walking the monkey falls sometimes to 
 one side and sometimes forward. The head hangs forward owing to 
 paralysis of the muscles of the neck. Movements of the tail are strong. 
 There is also a marked palsy of the lower part of the left facial nerve, 
 which is very obvious when the monkey is made to express pain. The left 
 angle of the mouth is not moved, nor does the lower part of the left cheek 
 show any trace of the wrinkling which is seen on the right side. In the 
 evening the monkey became moribund and was killed. 
 
 4 
 
5o 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 Unfortunately it was not possible to obtain a photograph of the facial 
 paralysis, because the animal was so ill that the expression of pain was only 
 momentary. Professor Miiller succeeded in the case of another monkey in 
 photographing a facial palsy, and with his permission I have reproduced 
 his photograph of a total right-sided paralysis. 
 
 Leiner and v. Wiesner have also observed facial palsy. 
 Levaditi and Stanesco have described a very beautiful case of which 
 they obtained a characteristic photograph (cf. fig. n). The 
 paralysis of the whole of the left facial nerve set in on the ninth 
 day after an intracerebral injection; the muscles of the eye were 
 
 Fig. io. 
 
 Monkey No. 102. 
 
 Right-sided facial paralysis. 
 
 likewise affected. The case is remarkable in that the facial palsy 
 was the first sign of the disease noticed, the paralysis of the limbs 
 following later. 
 
 Levaditi and Stanesco found marked changes in the ganglion 
 cells of the facial nerve. 
 
 Netter, as well as Flexner and Lewis, observed facial paralysis. 
 Flexner and Lewis give one illustration of the condition; the photo- 
 graph also shows a definite paralysis of the hypoglossal nerve, the 
 tongue deviates to the left, on which side the facial nerve was 
 paralysed (fig. 12). 
 
ETIOLOGY OF THE DISEASE 
 
 SI 
 
 Fig. n. 
 Left-sided facial paralysis. (After Levaditi and Stanesco.) 
 
 FIG. 12. 
 
 Paralysis of the facial and hypoglossal nerves on the left side. 
 (After Flexner and Lewis.) 
 
52 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 Monkey No 61 {Macacus rhesus) received on June 3, igio, an intra- 
 cerebral injection of '6 c.c. of a 5 per cent, emulsion of virus No. 11 (mixed 
 with normal human serum). 
 
 June 14-17. — No signs. 
 
 June 18. — Slight paresis of the right fore limb. During the afternoon 
 this became more marked and was definitely flaccid in type. The hind 
 limbs were, on the other hand, very markedly spastic ; the animal frequently 
 fell down when the hind limbs showed a strong tremor. In addition there 
 was a marked ptosis on the right side, the eyeball was deviated outwards 
 and downwards and could not be made parallel to the left eyeball. No 
 changes were observed in the pupils (fig. 13). 
 
 IWHP 
 
 Fig. 13. 
 
 Monkey No. 61. 
 
 Paralysis of the right oculomotor nerve. 
 
 June iq. — Found dead. 
 
 On microscopical examination considerable lesions were found in the 
 cerebral cortex and in the basal ganglia. The changes in the cord were 
 less marked. 
 
 In this case the oculomotor nerve was affected, and at the 
 same time the limbs were involved owing both to cerebral and spinal 
 lesions. 
 
ETIOLOGY OF THE DISEASE 53 
 
 Other cases were observed in which the disease was even more 
 definitely cerebral in type; cases analogous to the cerebral type of 
 Heine-Medin disease in man. 
 
 Monkey No. 27 (Mangabey) received on March 3, 1910, an intracerebral 
 injection of '6 c.c. of an emulsion of virus Xo. 12. 
 
 March 3-10. — Remained well. 
 
 March 11. — Depressed. 
 
 March 12. — Clearly ill, breathing heavily. 
 
 March 13. — Frequent tremor of the whole body. Walks stiffly and with 
 difficulty, but is not definitely paralysed. 
 
 March 14. — Lies on the floor; extremities show violent tremors and are 
 stiff. Died at 4 p.m. 
 
 On microscopical examination typical poliomyelitis. The changes affect 
 the pia mater in the region of the central gyri ; much perivascular infiltra- 
 tion in the cerebral cortex and in the basal ganglia. Very slight, apparently 
 only beginning, changes in the spinal cord. 
 
 Relatively seldom therefore a purely cerebral form of experi- 
 mental poliomyelitis occurs in monkeys. Flexner and Lewis record 
 similar cases in which, however, convulsions occurred, a thing I 
 never observed. Flexner found in eight out of eighty-one cases 
 that the disease began with cerebral or bulbar symptoms, although 
 these cases became later spinal in type. In one monkey in which 
 the paralysis was due chiefly to the cerebral lesions they observed 
 distinct nystagmus ; this is the only time that nystagmus has been 
 observed in a monkey so far as I know. 
 
 The symptom-complex due to cerebral localization of the lesion 
 of poliomyelitis in monkeys is by no means characteristic; in any 
 case caution is necessary in making the diagnosis of a purely cere- 
 bral lesion from the symptomatology alone in experimental polio- 
 myelitis; unless the diagnosis is controlled by microscopical 
 examination mistakes may easily occur. The following cases illus- 
 trate this point : — 
 
 Monkey Xo. 7 [Macacus rhesus) inoculated on December 17, 1909, with 
 ■5 c.c. of an emulsion of virus Xo. 11. 
 
 December 19. — Marked spastic paresis of the right hind limb and 
 moderate spastic paresis of the right fore limb. 
 
 December 20. — Condition the same. 
 
 December 21. — Paresis apparently less marked. 
 
 December 22. — Paralysis increased, the degree varies during the day. 
 
 December 23. — Found dead. 
 
 On examination none of the lesions typical of Heine-Medin disease were 
 found in the cerebral cortex or elsewhere. The paralysis was due to an 
 abscess, the size of a hazel-nut, in the region of the central gyri on the 
 left side at the site of the injection. From this abscess streptococci were 
 cultivated. 
 
 Monkey Xo. 60 [Macacus rhesus) inoculated on July 13, 1910, with 
 ■5 c.c. of emulsion of virus Xo. 11. 
 
 July 15. — Unsteady while jumping. 
 
 July 16. — Definite weakness of both left limbs. 
 
54 EPIDEMIC INFANTILE PARALYSIS 
 
 July 17-25. — Very marked paresis of the left fore limb, of a spastic 
 kind. 
 
 July 26-28. — Paralysis increasing. 
 
 July 29. — Found dead. 
 
 Microscopically no lesions indicative of poliomyelitis were found. In 
 the right central gyri at the point of inoculation an abscess the size of a 
 bean. 
 
 (e) Castro-intestinal Symptoms. — Diarrhoea coincident with 
 the paralysis has already been mentioned above, and in some of the" 
 cases reported. It is difficult to decide whether the poliomyelitis 
 is the cause of the diarrhoea because so many monkeys, when 
 bought recently, suffer from gastro-intestinal disturbance owing to 
 change of surroundings or of food. At the same time, the number 
 of cases in which diarrhoea occurred at the same time as paralysis is 
 so large, even in monkeys which had been kept in the institution for 
 a considerable time, that I have no doubt that the gastro-intestinal 
 symptoms are a part of the poliomyelitic infection. The following 
 are examples : — 
 
 Monkey Xo. 23 {Macacus rhesus) inoculated on January 20, 1910; 
 '5 c.c. into the brain and 5 c.c. into the peritoneum. 
 
 January 21-26. — No symptoms. 
 
 January 26. — In the evening the monkey seems more tired than usual. 
 
 January 27. — Sudden violent diarrhoea; at the same time total flaccid 
 paralysis of the hind limbs with slight paresis of the fore limbs. 
 
 January 28. — Diarrhoea has ceased. Paralysis of the hind limbs the 
 same, of the fore limbs more marked. Paralysis of the bladder. 
 
 January 29. — Complete paralysis of all limbs. Death during the after- 
 noon. 
 
 Microscopic appearances in the cord are typical. 
 
 Monkey Xo. 38 [Macacus rhesus). — Intracerebral inoculation on March 
 2, 1910, with '35 c.c. of an emulsion of virus Xo. 12 (mixed with serum from 
 a normal monkey). 
 
 March 3-9. — No symptoms. 
 
 March 10. — 111; takes food badly; severe diarrhoea; no paralysis. 
 
 March 11. — General condition the same. Unsteady gait. Resistance to 
 passive movement is diminished in all limbs. Xo definite paralysis observed 
 when walking. 
 
 March 12. — Monkey lies apparently completely paralysed on the floor 
 of the cage. Death 12 noon. 
 
 At the fost-mortem there was found severe gastro-enteritis with redness 
 and swelling of the follicles of the small intestine and of Peyers patches ; 
 the mesenteric glands were increased in size, being as large as beans. 
 Typical, but not intense, changes in the brain and spinal cord. Cultures 
 made from the blood and from the glands remain sterile. (Intracerebral 
 injection of material from the mesenteric glands into, another monkey pro- 
 duced typical poliomyelitis, cf. p. 98). 
 
 (f) Abortive Forms. — Wickman did great service in calling 
 attention to cases of Heine-Medin disease in man. in which there 
 are no definite symptoms of paralysis; he named this the abortive 
 
ETIOLOGY OF THE DISEASE 
 
 ;>o 
 
 type. In monkeys it is possible to produce a slight as well as a 
 severe form of the disease. It is difficult to decide whether true 
 abortive forms without paralysis occur in monkeys, because we have 
 no criteria by which we can determine the causal connection 
 between the general malaise and the injection of the virus. It may 
 be possible later to furnish proof by means of serum diagnostic 
 tests (vide infra). Personally I have no doubt at the present time 
 that such cases occur, because of the very slight and transient 
 palsies which I have observed. The following two examples may 
 be considered within certain limits to be cases of " abortive " 
 experimental poliomyelitis. 
 
 Fig. 14. 
 
 Monkey No. 44. 
 
 A trace of paralysis of the right hind limb. 
 
 Monkey No. 44 {Macacus rhesus), on March 23, 1910, intracerebral 
 injection of '6 c.c. of an emulsion of virus, also 3 c.c. into the peritoneum. 
 
 March 23-28. — No symptoms. 
 
 March 29. — The monkey appears more tired than usual. 
 
 March 30. — Severe diarrhoea. "Weakness of the right hind limb, 
 scarcely noticeable on walking, but obvious when the animal is sitting ; 
 the right leg cannot be adducted as strongly as the left. "Wherever one 
 places the monkey it always assumes this peculiar attitude, which is shown 
 well in the photograph (fig. 14). 
 
 March 31. — Diarrhoea less. Paralysis almost disappeared. 
 
 April 1 and subsequently. — Quite normal. 
 
56 EPIDEMIC INFANTILE PARALYSIS 
 
 Monkey Xo. 59 [Macacus rhesus). — Intracerebral injection on June 13, 
 igio, with '3 c.c. of emulsion of virus Xo. 11 (mixed with normal human 
 serum). 
 
 June 15-21. — Xo symptoms. 
 
 June 22. — Severe diarrhoea. 
 
 June 23. — Condition the same. 
 
 June 24. — Similar condition; in addition, slight paresis of the right 
 fore-limb. 
 
 June 25. — Unchanged. 
 
 June 26. — Paresis almost absent; diarrhoea less. 
 
 June 27. — Complete recovery. 
 
 That in this case the virus was responsible for the condition was proved 
 later. On reinoculation this animal remained well while the control died 
 [cf. p. 153). 
 
 Such abortive cases appear to be rare in monkeys. This may 
 be owing to the slighter symptoms being missed; even paralysis 
 can be observed with certainty only when it is fairly well marked. 
 In the last cases quoted above the paralysis was noticed because we 
 had already considerable clinical experience. Flexner and Lewis 
 have no doubt of the existence of abortive forms of experimental 
 poliomyelitis in monkeys. 
 
 In some cases I observed general weakness, the monkeys 
 looked ill and suffered from gastro-intestinal symptoms, but as no 
 paralysis occurred it was not possible to associate the symptoms 
 directly with the infection. I intended to test the immunity of these 
 animals by repeating the injection, but they died shortly afterwards 
 from tuberculosis of the lungs. In my statistics I have included 
 them among the unsuccessful inoculations. 
 
 (g) Marasmic Forms. — Leiner and v. Wiesner described this 
 form, but I have not had any opportunity of observing it. These' 
 authors describe it as follows: "After inoculation the animals 
 remained for some time well; towards the end of the incubation 
 period they became depressed, tired, suffered from diarrhoea (which 
 cleared up under treatment), wasted rapidly, did not care to move 
 about, were able to climb but did not wish to do so, the muscular 
 power was generally diminished; in one word, they became 
 marasmic. Some of them died between the sixth and thirteenth day 
 after inoculation without showing any signs of paralysis, others 
 lingered on for a longer time. Microscopical examination showed 
 beyond the possibility of doubt that these animals were suffering 
 from an atypical form of poliomyelitis. Besides hyperemia and 
 haemorrhages there was marked degeneration of the ganglion cells 
 with a certain amount of cell infiltration. We are convinced that 
 these animals succumbed to an atypical form of poliomyelitis with- 
 out paralysis. The striking feature of this form is the wasting of 
 the animals, and we have called it therefore the ' marasmic ' type." 
 Leiner and v. Wiesner have produced confirmatory evidence of their 
 contention by inoculating other monkeys with the spinal cord of 
 these, and finding that the new monkeys died of typical polio- 
 
ETIOLOGY OF THE DISEASE 57 
 
 myelitis. Eduard Miiller reports a human case in which he observed 
 marked general wasting although ample nourishment was taken. 
 He compares his case with those reported by the Austrian 
 observers. 
 
 (h) Recovery from the Acute Stage. — The foregoing types are 
 all characterized by the fact that almost all the monkeys succumbed 
 to the disease. In man it is more usual for life to be preserved, 
 even though the extent of the paralysis is considerable. In 
 monkeys such cases are rare; in my small amount of material I 
 saw one such case:- — 
 
 Monkey Xo. 37 (Macacus rhesus). — Intracerebral injection on March 2, 
 1910, with '3 c.c. of an emulsion of virus Xo. 12 (mixed with the serum of 
 a normal monkey). 
 
 March 3-8.— Healthy. 
 
 March g. — Marked weakness of the right hind limb ; left somewhat 
 weak. 
 
 March 10. — Flaccid paralysis of both hind limbs; severe diarrhcea. 
 
 March n. — Complete paraplegia. 
 
 March 12 and the weeks following. — The condition remained the same; 
 there was total flaccid paralysis of the hind limbs, while the rest of the 
 muscles acted well. On walking the hind limbs are dragged. Climbing 
 must be carried out by the arms alone and the monkey therefore soon 
 becomes tired. The monkey was cinematographed in this condition, and the 
 film was shown at the Congress for Internal Medicine at Wiesbaden in 
 April, 1910. Occasionally oedema of the legs was observed. This can be 
 explained by the position assumed by the monkey when sitting on its 
 board, the hind limbs hung down over the edge and the consequent com- 
 pression of the vessels caused the oedema. At the same time one must bear 
 in mind the possibility of vasomotor paralysis as a factor. The monkey 
 died on April 14 in a marasmic condition. 
 
 (i) Recovery from the Paralysis. — In other cases, as is so 
 
 common in man, we observed considerable improvement in the 
 paralysis. 
 
 Monkey Xo. 47 (Macacus rhesus). — On April 7, 1910, intracerebral 
 injection of '5 c.c. of emulsion of virus Xo. 11, also 4 c.c. into the peri- 
 toneum. 
 
 April 8-16. — Xo change. 
 
 April 17. — Slight weakness of left hind limb. Falls frecpuently while 
 climbing. In the afternoon paresis of both hind limbs. 
 
 April 18. — Marked flaccid paralysis of both hind limbs. The monkey 
 uses the arms only while climbing. 
 
 April 19-21. — Practically the same. The monkey walks with the arms 
 only, dragging the legs, which are completely flaccid. 
 
 April 22. — Condition the same; incontinence of urine. 
 
 April 26. — The left hind limb is used slightly; the right hind limb 
 appears cedematous at times. 
 
 May 2. — The paralysis of the left hind limb is much less and can be 
 observed only by testing the resistance of the limb to passive movements. 
 
 May 21. — Xo paralysis of the left hind limb; the right hind limb is still 
 completely paralysed. The photograph represents the monkey at this stage; 
 
58 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 the total paralysis of the right leg can be seen clearly on comparing the 
 attitude of the limb with that of the left leg which is normal (fig. 15). 
 
 Complete recovery from severe and extensive paralysis was 
 seen in the following cases : — 
 
 Monkey No. 32 {Macacus rhesus) on February 7, 19 10, received an intra- 
 cerebral injection of '5 c.c. of an emulsion of virus No. 12 which had been 
 warmed for half an hour at a temperature of 45 C. 
 
 February 8-14. — Quite well. 
 
 February 15. — Slight palsy of both hind limbs. 
 
 February 16. — Paralysis more marked. 
 
 February 17-20. — Condition unchanged. 
 
 February 21. — The paralysis is less; improvement more marked in the 
 right than in the left limb. 
 
 February 26. — Only a trace of weakness remains in the left hind limb. 
 
 March 12 onwards. — The monkey remained quite well. 
 
 Fig. 15. 
 
 Monkey No. 47. 
 
 Paralysis of the left hind limb. 
 
 Monkey No. 40 {Macacus rhesus). — On March 4, 1910, 
 injection of '6 c.c. of an emulsion of virus No. 12, also 4 
 peritoneum. 
 
 March 5-10. — No symptoms. 
 
 March 12. — Slight paralysis of both hind limbs. - 
 
 March 14. — Paralysis of both limbs well marked. 
 
 March 15-23. — Condition unchanged. 
 
 March 24. — Definite improvement in paralysis. 
 
 March 25 onwards. — The improvement is rapid. 
 
 April 3. — Paralysis entirely disappeared. 
 
 intracerebral 
 c.c. into the 
 
ETIOLOGY OF THE DISEASE 59 
 
 Monkey No. 41 {Macacus cynomolgus). — Intracerebral injection of 
 '6 c.c. of virus Xo. 11 on March 15, 19 10. 
 
 March 16-25. — No change. 
 
 March 26. — Slight paresis of hind limbs. 
 
 March 27. — Unchanged. 
 
 March 28. — Paresis of hind limbs more marked; definite slight paresis 
 of the right fore limb. 
 
 April 1. — Condition of hind limbs improved; the right fore limb now 
 total flaccid paralysis. 
 
 April 5 onwards. — Steady improvement in all the affected limbs. 
 
 May 5. — No paralysis in any limb. 
 
 Monkey No. 40 [Macacus rhesus) received an intracerebral injection ot 
 '6 c.c. of an emulsion of virus No. 12 on April 27, 1910. 
 
 April 28 to May 9. — No symptoms. 
 
 May 10. — Paresis of hind limbs, right more than left. 
 
 May 11-12. — No change. 
 
 May 13. — Paresis less, barely perceptible on left side. 
 
 May 14-15. — No change. 
 
 May 16. — Monkey climbs well ; there is still a slight weakness of the 
 left limb. 
 
 May 21. — No paralysis at all. 
 
 (k) Relapses. — One case may be quoted as a curiosity in which 
 there was a definite relapse ; the monkey appeared undoubtedly 
 to be recovering. Such a sequence of events is sometimes found 
 in human poliomyelitis. 
 
 Monkey No. 11 (Macacus rhesus). — Intracerebral injection of '5 c.c. of 
 an emulsion of virus No. 11 on December 8, 1909. 
 
 December 9-19. — No symptoms. 
 
 December 20. — Severe paralysis of right hind limb; perhaps also a 
 slight paresis of the arms. 
 
 December 21. — Marked paralysis of both hind limbs; slight paresis of 
 the arms. 
 
 December 22-25. — No change. 
 
 December 28 onwards. — Much improvement in all limbs; paresis in the 
 arms scarcely noticeable. The hind limbs are used occasionally. The 
 improvement is considerable. 
 
 January g. — Monkey becomes suddenly weaker. 
 
 January 10. — Hind limbs almost completely paralysed ; the animal drags 
 them after it. In the evening the fore limbs appear completely paralysed 
 and the monkey lies flat on the floor of the cage. 
 
 January 11. — Found dead. 
 
 Microscopical exmination shows typical acute changes in the spinal 
 cord. 
 
 Levaditi and Stanesco report a similar case. In a monkey 
 which became paralysed on the eleventh day after injection and 
 died on the twenty-ninth day in a condition of chronic paralysis, 
 they found both acute and chronic lesions in the spinal cord. 
 
 It is extremely difficult to say whether any disturbance of 
 sensation occurs in monkevs. Absolute and relative anaesthesia 
 
60 EPIDEMIC INFANTILE PARALYSIS 
 
 cannot be tested for with any certainty. It appears to me, however, 
 that shortly before the paralysis appears there is a stage of hyper- 
 sesthesia similar to that observed in man on which Eduard Miiller 
 lays so much diagnostic stress. Monkeys, which previously had 
 been quiet and friendly, uttered loud cries when they were touched 
 or when the attempt to capture them made them move about. 
 
 It is quite certain, from our purely clinical observations, that 
 in monkeys the spinal symptoms of the disease are the most 
 marked, whether the monkeys are infected via the brain or 
 the brain and peritoneum at the same time. According to other 
 authors it does not matter whether the injection is made into the 
 subcutaneous tissue, the nerves, or the eyeball; the picture is 
 always essentially one of spinal paralysis. Usually the paralysis 
 is of the ascending type and causes death by involvement of the 
 medulla with consequent respiratory paralysis. Occasionally bulbar 
 signs (facial palsy, &c.) are observed; the combination of bulbar 
 and spinal symptoms produces a clinical picture similar to that of 
 Landry's disease in man. Finally, there can be no doubt that 
 monkeys are subject to a purely cerebral form of the disease, 
 analogous to the rare human cases of cerebral Heine-Medin 
 disease. Marasmic, abortive and relapsing forms of the disease 
 have been observed. In short, clinical investigation of cases of 
 experimental poliomyelitis in monkeys reveals types similar to the 
 manifold forms of Heine-Medin disease in man, and the point of 
 entry of the virus does not influence the result. 
 
 Prognosis. — One important point of difference between human 
 poliomyelitis and the experimental disease in monkeys is the 
 mortality. The figure varies in human beings, as has been shown 
 above. It lies between 10 and 20 per cent., when only those cases 
 are counted in which paralysis has occurred. Similar statistics in 
 monkeys show a much less favourable figure. In my own 
 monkeys, counting only those in which paralysis appeared, I find 
 that /6'4 per cent, died of the paralysis, 6 per cent, survived 
 paralysed and i/'6 per cent, recovered completely- These figures 
 are very similar to those obtained by Flexner and Lewis. They 
 found that 75 per cent, of all cases with paralysis died. This 
 figure, however, is only an estimate, because they killed many of 
 their animals for purposes of investigation. I myself waited in 
 almost every case until the animal was moribund before killing it. 
 My figures are consequently quite reliable. Flexner and Lewis 
 state that by passing a virus through many animals they obtained 
 finally a mortality of 100 per cent. The prognosis in experimental 
 poliomyelitis of monkeys is therefore much less favourable than 
 that of natural poliomyelitis in man. This is of importance in 
 judging of the value of any therapeutic measures when applied to 
 the experimental disease. 
 
 Fig. 16 shows clearly the relations between duration of in- 
 cubation and duration (i.e., severity) of paralysis; it illustrates the 
 question of recovery and duration of paralysis. 
 
ETIOLOGY OF THE DISEASE 
 
 61 
 
 According to this table a short incubation period corresponds 
 to a short violent course of the disease. In the case of monkey 
 No. 2>7 > however, a short incubation period did not mean a sub- 
 sequently fatal attack. Further consideration of the table shows 
 that there is no fixed correspondence between the length of the 
 incubation period and the severity of the attack. Monkeys Nos. 
 13, 11, and 35, with incubation periods of 10J, n\, and 15 days 
 respectively, suffered from a long paralytic stage, which ended 
 fatally; but. on the other hand, the monkeys Nos. 2 and 36 had 
 an equally long incubation period and yet died very rapidly. We 
 find also that in some cases (monkeys Nos. 32 and 40), in spite 
 of a relatively short incubation period, the disease ended in com- 
 plete recovery. 
 
 MonkeyN 1 . 
 Days 
 
 Period of incubation. 
 
 ,, paralysis ending in death. 
 
 ,, non-fatal paralysis. 
 
 Fig. 16. 
 
 The conclusion to be drawn from these experiments is that 
 no rules for prognosis can be formulated which are based upon 
 the length of the period of incubation. 
 
 III.— THE NATURE OF THE VIRUS. 
 
 The results of my first experiments convinced me that the 
 virus of poliomyelitis must be fairly stable. I was successful in 
 the case of monkey No. 1 in inoculating a virus which had been 
 kept for forty-eight hours after the autopsy, and with monkey 
 No. 2 in inoculating one kept for sixty-four hours. Flexner and 
 
62 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 Lewis came to the same conclusion; they used a virus which was 
 thirty-eight hours old. Landsteiner and Levaditi used a virus four 
 days after the death of the child in their original experiment. In 
 his fundamental work Landsteiner, together with Popper, made 
 the suggestion that the cause of Heine-Aledin disease belonged to 
 the group of viruses capable of filtration. The following experi- 
 ments prove the correctness of his suggestion. 
 
 Filtration Of the Virus. — Flexner and Lewis demonstrated 
 simultaneously with and independently of Landsteiner and Levaditi 
 that the virus would pass through various filters which were fine 
 enough to hold back bacteria. I give below the tabulated results 
 of Landsteiner and Levaditi's experiments; from them can be seen 
 the difference in virulence between the filtered and unfiltered virus. 
 
 Name of filter 
 
 (Berkefeld ... 
 
 (Control 
 
 fBerkefeld ... 
 b \ Chamberland 
 I Control 
 
 fBerkefeld I 
 c\ „ II 
 
 (Control 
 
 (Reichel A ... 
 d\ ,, B ... 
 (Control 
 
 Monkey 
 
 Macacus cvnomoleits N> 
 
 Callitrichus No. 26 
 „ 27 
 
 iS 
 
 19 
 100 
 
 Macacus sinicus No. 
 
 ! ) • ! 5 ) 
 
 , , rhesus , , 
 
 28 
 31 
 
 Macacus rhesus No. 23 
 Macacus cynomolgus No. 24 
 Mandrill No. 2; 
 
 Incubation 
 period 
 
 8 d 
 
 ays 
 
 16 
 8 
 
 11 
 8 
 4 
 
 + in 5 days 
 Survived 
 + in 2 days 
 
 Survived 
 + in 1 day 
 + in 2 days 
 
 + in 15 days 
 + in 2 ,, 
 
 + in 7 ,, 
 
 + in 5 days 
 
 Killed 
 
 + in 1 day 
 
 Landsteiner and Levaditi and also Flexner and Lewis proved 
 that a living" virus was present in the filtrate and not merely a toxin 
 contained in the spinal cord, by injecting the spinal cord substance 
 of monkeys infected with the filtrate into other monkeys with a 
 positive result. 
 
 Leiner and v. Wiesner at first obtained negative results when 
 using Reichel filters; later they obtained positLe results with virus 
 passed through Pukall filters. Their results show the influence of 
 filtration upon the length of the incubation period. 
 
 Inoculation with filtrate 
 
 Inoculation with unfiltered emulsion 
 
 Monkey No. 
 
 Incubation period 
 
 Monkey No. 
 
 Incubation period 
 
 22 
 23 
 36 
 41 
 
 10 days 
 
 15 ,. 
 12 ,, 
 
 11 ,, 
 
 21 
 21 
 
 37 
 40 
 
 8 days 
 8 „ 
 7 ,. 
 6 ,, 
 
ETIOLOGY OF THE DISEASE 63 
 
 The period of incubation is longer when the filtered virus is 
 used, as can be seen from both tables. Flexner and Lewis state 
 further that when they used virus which had been intensified by 
 being" passed through many animals, a very small dose of the 
 filtrate produced severe paralysis after an incubation period of the 
 usual length; they conclude that the virus must be extraordinarily 
 fine. 
 
 Personally, I had but little success with emulsions filtered 
 through a Berkefeld filter; I was able only indirectly to prove 
 that the filtrate contained the virus by showing" that a monkey 
 which had been inoculated with it without result was immune to a 
 lethal dose of the emulsion. 
 
 These experiments prove that the virus is capable of passing 
 through filters like the Berkefeld, Chamberland, Reichel, and 
 Pukall filters, through all of which bacteria cannot pass. 
 
 Resistance to Glycerine. — In its behaviour towards filters the 
 poliomyelitis virus shows again its similarity to the virus of rabies; 
 on the whole it seems to pass through filters more easily than the 
 latter virus. This led to further experiments being made to 
 discover further similarities. One of the most important of these 
 is the resistance shown towards glycerine. Landsteiner and 
 Levaditi made the first experiment ; ' in their first experiment they 
 used with success a virus which had been preserved in 33 per cent. 
 glycerine for four days, in order that it might be sent from Vienna 
 to Paris. We ourselves, usually against our inclination and only 
 because our modest means did not always allow us to inoculate 
 direct from one monkey to another, had ample opportunity of 
 studying the resistance to glycerine of our virus. In the following 
 table I have put together all the injections in which virus preserved 
 with glycerine was used; each original virus is placed in a separate 
 table. 
 
 It is clear that the virus remains potent for at least ninety-one 
 days when kept in 50 per cent, glycerine, but this does not represent 
 the limit of time that it can be kept (cf. monkeys Nos. 46, 59, and 
 61). Although the inoculation of monkey No. 44 with virus which 
 had been kept for 95 days resulted only in a doubtful illness, the 
 reason of this is to be found rather in a peculiar resistance of this 
 particular animal than in the virus itself. The experiments with 
 virus No. 6 shows that 142 days in pure glycerine is not enough 
 to cause any diminution of potency. There is some slight differ- 
 ence in behaviour towards glycerine between the virus obtained direct 
 from man and that obtained from inoculated animals. Yet experi- 
 ments with virus Nos. 11 and 12 show that after passing through 
 five and six animals the virus resists glycerine as well as the 
 original virus (cf. monkeys Nos. 59 and 61). 
 
 These results correspond with those obtained by Landsteiner 
 and Levaditi; these authors supplement my figures in so far as 
 they used 33 per cent, glycerine in their experiments. They proved 
 that the virulence was not affected after seven, nine, and twenty- 
 
6 4 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 two days in 33 per cent, glycerine. Flexner and Lewis also have 
 proved the resistance of the virus to glycerine. 
 
 The discovery of this fact is of great practical importance; 
 experimental work is rendered easier by the knowledge that direct 
 inoculation from monkey to monkey is not necessary. Glycerine 
 
 Virus No. 11. 
 
 Preserved in 50% Glycerine. 
 
 No. of monkeys 
 
 No. of 
 
 Method of 
 
 Length of time 
 
 Length of 
 
 Duration of the 
 
 passed through 
 
 monkey 
 
 infection 
 
 in glycerine 
 
 incubation period 
 
 fatal illness 
 
 Original virus 
 
 44 
 
 i-c. and i-p. 
 
 95 da ys 
 
 12 days 
 
 Abortive p.m. ? 
 
 III 
 
 23 
 
 ,, 
 
 14 ,, 
 
 5i ,. 
 
 3 days 
 
 III 
 
 46 
 
 
 9i „ 
 
 8 ,, 
 
 5 » 
 
 V 
 
 47 
 
 )» 
 
 24 ,, 
 
 9 „ 
 
 Survived 
 
 V 
 
 48 
 
 ,, 
 
 24 ,, 
 
 9 ,, 
 
 2 days 
 
 V 
 
 58 
 
 l-C. 
 
 78 „ 
 
 10 ,, 
 
 2 ,, 
 
 V 
 
 59 
 
 
 9i „ 
 
 10 ,, 
 
 Survived 
 
 V 
 
 61 
 
 ,, 
 
 91 >. 
 
 4 ,, 
 
 ih days 
 
 VI 
 
 56 
 
 i-c. and i-p. 
 
 30 ,, 
 
 13 „ 
 
 9 » 
 
 Virus No. 12. 
 
 Preserved in 50% Glycerine. 
 
 Xo. of monkeys 
 
 No. of 
 
 Method of 
 
 Length of time 
 
 Length of 
 
 Duration of fatal 
 
 passed through 
 
 monkey 
 
 infection 
 
 in glycerine 
 
 incubation period 
 
 illness 
 
 Original virus 
 
 21 
 
 l-c. and i-p. 
 
 31 
 
 days 
 
 9 days 
 
 i\ days 
 
 11 
 
 29 
 
 l-C. 
 
 8 
 
 ,, 
 
 8 ,, 
 
 7 ,. 
 
 II 
 
 27 
 
 ,, 
 
 3i 
 
 
 , 
 
 8 ,, 
 
 4 >> 
 
 II 
 
 37 
 
 ,, 
 
 3i 
 
 
 
 6 ,, 
 
 Survived 
 
 II 
 
 38 
 
 ,, 
 
 3i 
 
 
 , 
 
 8 „ 
 
 2it days 
 
 II 
 
 40 
 
 i-c. and i-p. 
 
 33 
 
 
 , 
 
 7 „ 
 
 Survived 
 
 III 
 
 43 
 
 ,, 
 
 8 
 
 
 , 
 
 9 ,, 
 
 Abortive p.m. 
 
 III 
 
 42 
 
 l-C. 
 
 10 
 
 
 , 
 
 10 ,, 
 
 i\ days 
 
 III 
 
 35 
 
 -c. and i-p. 
 
 20 
 
 
 , 
 
 15 » 
 
 I? !! 
 
 A" 
 
 49 
 
 l-C. 
 
 24 
 
 
 ' 
 
 12 ,, 
 
 Survived 
 
 Virus No. 6. 
 
 Preserved in Concentrated Glycerine. 
 
 Xo. of monkeys Xo of Method of Length of time 
 
 passed through j monkey infection in glycerine 
 
 Length of Duration of fatal 
 
 incubation period j illness 
 
 i-c. and i-p. 59 days 
 142 ,, 
 
 10 days 
 54 „ 
 
 5 days 
 I day- 
 
 Can be used as a preservative when the virus has to be sent from 
 place to place. Especially is it important in cases of suspected 
 Heine-Medin disease, when the virus may be kept in 50 per cent. 
 glycerine until a monkey can be procured. Preservation in glycerine 
 may be used for material that has become contaminated with 
 bacteria; in 50 per cent, glycerine the bacteria are slowly destroyed. 
 
ETIOLOGY OF THE DISEASE 05 
 
 The Effect of Low and High Temperatures— The behaviour 
 of the virus towards different temperatures presents various points 
 of interest. The above figures relating to the resistance to 
 glycerine provide some data owing to the fact that all the pre- 
 parations were kept in the dark in an ice-chest. It follows that a 
 temperature of + 4 C. is not inimical to a virus preserved in 
 glycerine. Flexner and Lewis found that keeping the virus itself 
 at the temperature of an ice-chest for fifty days had no effect upon 
 its virulence; even complete mouldiness of the pieces of spinal 
 cord containing virus did not influence the activity of the virus. 
 They kept virus at a temperature of between — 2° and — 4 f or 
 forty days and still found it virulent. Leiner and v. Wiesner used 
 a virus which had been kept for four hours in a freezing mixture; 
 an intracerebral injection produced slight paralysis after an incuba- 
 tion period of twelve days. Landsteiner and Levaditi quote one 
 case in which the virus was kept for eleven days in the frozen 
 state and then caused paralysis of the hind limbs after an incubation 
 period of six days; the animal survived. 
 
 These experiments prove that the virus of Heine-Medin disease 
 is but little affected by low temperatures. As will be seen later,, 
 this has some bearing on the question of epidemiology. 
 
 There is some accidental evidence showing the behaviour of 
 the virus towards moderate temperatures. Landsteiner and 
 Levaditi, in the course of their attempts to obtain an attenuated 
 virus by methods similar to that employed by Pasteur in the case 
 of rabies, found the virus fully virulent after nine days, at a 
 temperature of 22 C. In his experimental " cultures," quoted on 
 pag'e 29, Levaditi showed that the virus resisted a temperature of 
 37 for at least fifteen days. 
 
 The virus appears to be much affected by temperatures higher 
 than these. We have made systematic experiments to elucidate 
 this point. 
 
 Experiment 1. — Monkey No. 32 received an intracerebral injection on 
 February 7, 1910, of '5 c.c. of a 5 per cent, emulsion of brain and spinal 
 cord heated for half an hour to a temperature of 45 . The material was 
 obtained from monkey 24 (virus No. 12 passed through two animals). On 
 February 15 paresis of the hind limbs, increasing for a few days, dimin- 
 ishing from February 22 onwards until March 12. No paralysis is present. 
 The control, monkey 29, received '35 c.c. of the same virus unheated, 
 became paralysed on the 13th and died on the 15th (vide p. 47). 
 
 Experiment 2. — Monkey 51, on April 25, 1910, received an intracerebral 
 injection of '5 c.c. of 5 per cent, emulsion from monkey 36 (virus No. 11 
 passed through five animals]. The emulsion was heated for half an hour at 
 temperature of 50 . The animal remained well. The same virus, injected un- 
 heated on May 31, 1910, into monkey 58, proved highly virulent (vide p. 77). 
 
 Experiment 3. — Monkey 26, on January 25, 1910, received '5 c.c. of 
 10 per cent, emulsion of brain and cord of monkey 21 (virus No. 12 passed 
 
66 EPIDEMIC INFANTILE PARALYSIS 
 
 through one animal). The emulsion was heated for half an hour at 55 . The 
 animal remained well. Monkey 24 injected on the same day with the same 
 amount of virus unheated became paralysed in both legs on the fourth day 
 and died on the fifth. Microscopical appearances typical. 
 
 When heated for half an hour at 45 the virus is still virulent, 
 although somewhat attenuated; heating for half an hour at 50 
 or 55 was sufficient to destroy its virulence. 
 
 Leiner and v. Wiesner obtained similar results. They found 
 the virus no longer virulent after being heated to 50 for one 
 hour and to 6o° for fifteen to twenty minutes. It was due probably 
 to some peculiarity in the animal used that they found in one 
 instance that heating for two hours at a temperature of 35 
 destroyed the activity of the virus; Levaditi's experiment, quoted 
 above, with virus at 37 , and my own experience with virus kept 
 at 45 , confirm this view. Flexner and Lewis report that warming 
 at 45 to 50 for half an hour destroys the potency of the virus; 
 this corresponds more or less with our own results. 
 
 Resistance to Drying. — The evidence on this point is some- 
 what conflicting. The following is my own experiment : — 
 
 Monkey 36 {Macacus rhesus) was injected with virus No. 11 on 
 February 26, iqio. The virus was obtained from the cord of a monkey 
 which had been dried in vacuo for twenty-eight days at room temperature 
 and guarded from light. After an incubation period of thirteen days 
 paralysis of the right fore limb and of both limbs appeared; on 
 March 13, total paralysis of the hind limbs; on March 14, paralysis of all 
 limbs; death on March 15. Histological appearances typical. 
 
 Spinal cord dried for twenty-eight days in vacuo was found 
 therefore to be virulent. The experience of other authors has 
 been similar. Flexner and Lewis dried the virus for seven days 
 over caustic potash and found it virulent; Landsteiner and Levaditi, 
 following Pasteur's method, dried a cord over caustic potash in 
 one case for nine days, in another for twenty-four days, at a tem- 
 perature of 22 . In both experiments the cord was found to be 
 virulent. They emphasise the difference in this respect of the virus 
 of Heine-Medin disease and the virus of rabies. In another experi- 
 ment they dried a thick layer of emulsion of virulent spinal cord 
 in vacuo at room temperature and found it fully virulent at the 
 end of fifteen days. 
 
 On the other hand, Leiner and v. Wiesner obtained a different 
 result. They dried a thin layer of emulsion in an incubator at 
 .37° for four hours and found it non-virulent. In another instance 
 they allowed a thin layer of emulsion of spinal cord to dry for twenty- 
 four hours at the temperature of the room; the dried emulsion was 
 washed off and injected with a negative result (unfortunately, they 
 do not give any report of a control experiment). In this experi- 
 ment they were attempting to reproduce the natural conditions and 
 it is possible that in a very thin layer the emulsion withstands 
 
ETIOLOGY OF THE DISEASE 67 
 
 drying less well. From this point of view it would be worth while 
 to corroborate and amplify their results. 
 
 Behaviour towards Disinfectants. — I have not been in a posi- 
 tion to make extended experiments on the behaviour of the virus 
 of poliomyelitis towards disinfectant chemicals, although the 
 subject is of the greatest importance for many reasons, particularly 
 from the point of view of prophylaxis. I made experiments with 
 formalin. The chemical was not mixed directly with the virus, 
 but an active emulsion was exposed to the vapour in the course 
 of a test disinfection of a room which will be described later. The 
 virulence of the emulsion was found to have been destroyed. The 
 most complete investigations into the effect of chemicals upon the 
 virus have been made by Landsteiner and Levaditi. Their first 
 experiments were made with menthol oil and with a powder com- 
 posed of menthol, salol, and boric acid. Two cubic centimetres of 
 an emulsion of virulent virus was shaken with "5 c.c. of a 1 per 
 cent. solution of menthol oil and allowed to stand for two hours 
 at room temperature. A monkey which received an intracerebral 
 injection of "5 c.c. of this mixture showed only slight transient 
 symptoms; the control animal became paralysed on the fourth day 
 and died on the sixth. In a second experiment 2 c.c. of the same 
 emulsion was mixed with "05 grm. of the powder ("2 grm. menthol, 
 5 grm. salol, 20 grm. boric acid), well shaken and kept at room 
 temperature for two hours. The monkey injected with this also 
 suffered from transient symptoms. 
 
 A 1 in 1,000 watery solution of thymol mixed with an equal 
 quantity of emulsion for one hour at 37 did not diminish the 
 virulence. The activity of the virus was destroyed after mixture 
 with a 2 per 1,000 solution of potassium permanganate for one 
 hour at 37 . A 1 in 5 (6 per cent.) dilution of perhydrol (Merck) 
 mixed with an equal part of emulsion for forty-five minutes at 
 37 killed the virus. Flexner and Lewis found a 1 per cent, solu- 
 tion of H 2 2 was effective, but do not give the length of contact 
 necessary. 
 
 Of some importance with regard to personal prophylaxis is 
 the discovery by Landsteiner and Levaditi of the efficacy of 
 potassium permanganate and peroxide of hydrogen. 
 
 Kraus investigated the influence of carbolic acid on the virus. 
 He found that the filtered emulsion is more easily killed than the 
 unfiltered; this is due to the presence in the latter of coarser 
 particles of the spinal cord, which enclose the virus and prevent 
 the carbolic from acting on it. Contact with a '5 per cent, solution 
 of carbolic acid for five days lessened the virulence and in some 
 cases destroyed it. A i per cent, solution did not kill the virus 
 in one to three days, but it was efficacious in four to five days. 
 
 The Durability of the Virus in Animals. — My own material 
 bearing on this point is small. In general I used only the emul- 
 sions obtained from the brain and cord of animals which had 
 died acutely for further injections. The spinal cord of monkeys 
 
68 EPIDEMIC INFANTILE PARALYSIS 
 
 which had died on the fourth day after infection proved fully 
 virulent. That the virus can remain virulent for a long time within 
 the body of the animal is proved by the case reported above {vide 
 p. 59); monkey 11 received an intracerebral injection on Decem- 
 ber 8, 1909; paralysis set in on the 26th and then improved 
 for a time ; on January 9 a definite relapse occurred and the animal 
 died on January 11. The typical appearances of acute poliomyelitis 
 found in the spinal cord, together with the results of further 
 injections into other animals, proved that the virus was still fully 
 virulent after thirty-three days. Leiner and v. Wiesner found potent 
 virus in the cord of an animal which had been ill for twenty-four 
 days. It is probable, however, that these results do not represent 
 the normal condition of affairs; relapses are very rare in monkeys 
 and I have only seen one case. In another case Leiner and v. 
 Wiesner found that the spinal cord of a monkey, which had 
 suffered from paralysis for only six days, was no longer virulent; 
 the monkey which was injected with this cord showed no signs 
 of paralysis up to the twenty-fourth day. Landsteiner and Levaditi 
 found virulent spinal cord on the fourth day after injection, but 
 thirty-nine to forty-five days later they found no virulence. 
 
 Xo rule as to the viability of the virus in monkeys can be 
 formulated from the small amount of material available. There is 
 a wide field for further investigation in this direction. Landsteiner 
 and Levaditi suppose that the virus usually disappears at the end 
 of the acute stage, but that in isolated instances this does not 
 take place. 
 
 The virus appears to remain longer in regions other than the 
 central nervous system. Flexner reports that Osgood and Lukas, 
 two American investigators, found the mucous membrane of the 
 pharynx virulent six months after the monkey had received an 
 intracerebral injection, and at a time when the virus had completely 
 disappeared from the central nervous system. In another case the 
 brain, spinal cord, and mucous membrane of the nose and throat 
 were all virulent eight weeks after the intracerebral injection. 
 
 The Effect of passing the Virus through Animals. — The 
 question whether the biological characteristics of the virus become 
 altered when it is passed through animals is of great interest. 
 The material available is not large. According to my own experi- 
 ence the behaviour towards glycerine is the same in the original 
 virus and in virus which has been passed through animals; I have 
 found no constant difference in virulence (pathogenic energy) 
 towards monkeys between them. Leiner and v. Wiesner found no 
 diminution of virulence after a " long " series of reinoculations. 
 Flexner and Lewis, who have passed virus through longer series 
 of animals than anyone else, have come to the conclusion that the 
 virus becomes more powerful, or, at any rate, loses none of its 
 potency and becomes more constant in its effect. This increase in 
 constancy is shown in three ways: (1) The higher proportion of 
 fatal cases; (2) the higher percentage of successful intracerebral 
 
ETIOLOGY OF THE DISEASE 69 
 
 inoculations (100 per cent, instead of 75 per cent, with the original 
 virus) ; and (3) a greater uniformity in the duration of the incubation 
 period. These experiences remind one of the results obtained by 
 Pasteur in hydrophobia; he found that the virulence towards rabbits 
 was increased by passing the virus through a large number of 
 rabbits; intracerebral inoculation acted more certainly and with a 
 shorter incubation period. We know now, however, that the term 
 exaltation of the virus must be used cum grano, because the 
 " exalted " virus is less potent than the ordinary kind, when 
 administered subcutaneously. At any rate, some peculiar biological 
 change does take place in the virus, and we are inclined to regard 
 it as the essential factor underlying protective inoculation against 
 hydrophobia. The observations of Flexner and Lewis make it not 
 improbable that continued passage through monkeys causes some 
 biological change in the pm. virus, turning it into a kind of 
 " virus fixe," as shown by the greater constancy of the incubation 
 period, of the morbidity and of the mortality. Further investiga- 
 tions must be made to find out if the changes produced in this 
 manner can be demonstrated by other means. 
 
 Flexner and Lewis have called attention to a point which is 
 of importance in this connection. They assume that the sudden 
 change from man to monkey (" change of host ") must have a con- 
 siderable effect upon the virus because it is so often destroyed in the 
 process. My own experience confirms this in some measure; cf 
 the five original examples of virus I succeeded in transmitting only 
 three to monkeys. We must regard it as a possibilhy that the 
 transference of the virus to monkeys causes some biological change 
 in the virus. The present state of our knowledge does not admit 
 of any more definite statement. A wide field is left open in this 
 direction also to future experimenters. 
 
 IV.— THE USE OF OTHER ANIMALS FOR 
 EXPERIMENT. 
 
 The Susceptibility of Different Animals. — It would be a great 
 advantage if some other animal, more easy to obtain and keep and 
 less costly, could be submitted for the monkey. I have experi- 
 mented with white mice, guinea-pigs, sheep, goats, and dogs; using 
 the method of intracerebral injection, which proved the best in the 
 case of monkeys, I nevertheless was unable to produce any sym- 
 ptoms of poliomyelitis in these animals. In all the experiments the 
 brain and spinal cord emulsions proved entirely non-virulent, 
 although the same emulsion injected into monkeys produced 
 typical lesions of poliomyelitis. Other observers (Leiner and v. 
 Wiesner, Landsteiner and Levaditi, Krause and Meinicke, Flexner 
 and Lewis) obtained the same negative results. Flexner and Lewis 
 even used pigs, horses, cows, and cats; they observed the animals 
 for weeks after the injection but they never saw any paralysis. 
 
JO EPIDEMIC INFANTILE PARALYSIS 
 
 Leiner and v. Wiesner, and also Landsteiner and Levaditi, used 
 young dog's and injected the virus both into the brain and the 
 peritoneum, but they obtained no single positive reaction. The 
 same authors and Krause and Meinicke have proved that fowls 
 and pigeons are not susceptible. It is quite certain therefore that 
 all the animals mentioned are not susceptible to the virus of 
 poliomyelitis. This negative finding is of importance in judging 
 the assumption which is made frequently, that the occurrence of 
 paralysis in animals, particularly fowls and dogs, can be connected 
 with epidemics of Heine-Medin disease. 
 
 Earlier Experiments with Rabbits. — There has been much 
 controversy about the susceptibility of rabbits. The rabbit was 
 the first animal used for experimental injection of material 
 obtained from children who had died of paralysis. The first 
 attempt was made in 1899 by Biilow-Hansen and Harbitz. They 
 injected emulsion of the spinal cord and cerebro-spinal fluid into 
 rabbits and mice, using the intracerebral method among others. 
 The results were all negative. The experiments of Guinon and 
 Rist (1903), in which cerebrospinal fluid from cases of poliomyelitis 
 was injected into rabbits, led to no positive results. In 1908, 
 Pasteur, Foulerton, and MacCormac reported positive results with 
 rabbits for the first time. They injected cerebrospinal fluid, 
 obtained eleven days and four weeks after the commencement of 
 the disease, into rabbits; in some the injection was subcutaneous, 
 in others intraperitoneal, and finally intracerebral. Many of these 
 animals became paralysed some time after the injection; the 
 authors report that in a few cases they were able to infect other 
 rabbits with the cerebrospinal fluid of these first rabbits, but that 
 it was not possible to transmit the disease to a third generation. 
 Histological examination of the spinal cord of one of the paralysed 
 rabbits showed ho changes characteristic of poliomyelitis. 
 
 Krause and Wernicke's Experiments with Rabbits. — The 
 experiments of the English authors raised hopes that poliomyelitis 
 might be produced experimentally in rabbits and their experiments 
 were repeated by Krause and Meinicke in the summer of 1909 at 
 the time of the great Westphalian epidemic. These authors used 
 "large doses" of cerebrospinal fluid obtained from autopsies or 
 by lumbar puncture; the injections were intraperitoneal, intravenous 
 or subdural. Very many of the animals became ill after the in- 
 jection, and Krause and Meinicke observed " a certain regularity in 
 the period of time elapsing before the illness began, in the 
 character of the symptoms and in the total duration of the illness. 
 Death was ushered in by symptoms which pointed to a lesion of 
 the spinal cord." In their first paper Krause and Meinicke do not 
 record any microscopical examinations. They found that spleen 
 pulp, blood, and cerebrospinal fluid of rabbits dying of polio- 
 myelitis were suitable for further transmission of the disease as 
 well as the brain and spinal cord. It is to be noted that the disease 
 consisted of the above peculiar symptoms. 
 
ETIOLOGY OF THE DISEASE 7 1 
 
 Results Of Personal Experiments. — In my first experiments 
 I used rabbits bred in the laboratory. The animals were full grown 
 and weighed from 2,000 to 3,000 grin. I chose adult rabbits which 
 were already acclimatized to the laboratory, because young rabbits 
 are known to succumb readily to secondary infections. The first 
 experiments with their results are as follows : — 
 
 Experiment 1. — Cerebrospinal fluid was obtained by lumbar puncture 
 from a 3-year-old child who had suffered from paralysis for three weeks 
 and was in the chronic stage of the disease. The fluid was kept in an 
 incubator at temperature 37° for ten days in order to " exalt " the virus. 
 An intracerebral injection of '2 c.c. was made into two rabbits. Both 
 animals remained quite well. 
 
 Experiment 2. — Fluid was obtained by lumbar puncture from a very 
 acute and extensive case which died twenty-four hours later and showed 
 typical microscopial changes in the cord. The virus was " exalted " for 
 seven days, as in Experiment 1, and '2 c.c. was injected into two rabbits. 
 Both remained well. 
 
 Experiment 3. — '2 c.c. of the fluid from the case used in Experiment 1, 
 but obtained fourteen days later, was injected into two rabbits. The one 
 died of suppuration from a bite on the abdomen ; on microscopical examina- 
 tion the brain and spinal cord were normal. The other animal remained 
 well. Two other animals received an intracerebral injection of '2 c.c. of 
 the same virus passed through a Berkefeld filter; they remained well. 
 Finally '2 c.c. of the blood of this case was injected into a rabbit, which 
 remained unaffected. 
 
 Experiment 4. — Fluid was obtained from a baby, 9 months old, suffering- 
 from paralysis of moderate degree for seven days. Two rabbits each 
 received an intracerebral injection of '1 c.c. and both remained well. 
 
 These results contradict the experience of Krause and Meinicke, who 
 found cerebrospinal fluid suitable for the transmission of the disease. It 
 should be noted further that in some of my experiments the fluid was 
 obtained from acute and severe cases. The attempt to. " exalt " the virus 
 in the incubator cannot have affected its virulence. The entirely negative 
 character of the results made me sceptical about those reported by Krause 
 and Meinicke. On the other hand, this fact proved nothing against the 
 possibility that rabbits might be susceptible to the disease and so of use in 
 research. On the one hand, it was doubtful if the cerebrospinal fluid con- 
 tained virus at all, and, on the other hand, whether it contained a sufficient 
 quantity of the virus. 
 
 In my subsequent experiments I always used material which 
 I was certain contained virus, i.e., emulsion of the brain and 
 spinal cord of human beings and monkeys known to have died 
 of the disease. 
 
 Experiment 5. — An emulsion of virus No. 6 was injected into six 
 rabbits, two by intravenous injection ('5 c.c), two intraperitoneal ('5 c.c), 
 and two intracerebral ('2 c.c). All remained well, although a monkey 
 
72 EPIDEMIC INFANTILE PARALYSIS 
 
 injected with the same material died of acute, severe poliomyelitis, and 
 material from this monkey proved fully virulent. 
 
 In consequence of these results 1 felt bound to advise caution 
 in judging" of the value of reports of positive results obtained with 
 rabbits. The rabbit is known to be a very sensitive animal and 
 this has several times led to much confusion in etiological in- 
 vestigations; the French have even called it an " animal capricieux." 
 
 Subsequent investigations confirmed my previous conclusions. 
 Each original virus, which I described on pp. 34-42, was injected 
 into rabbits as well as into monkeys. I shall not describe 
 the results obtained with virus 2 and 3, because no definitely 
 positive result was obtained with these in monkeys. Injection of 
 these strains into rabbits remained without any effect. The follow- 
 ing description relates only to those strains with which a positive 
 result was obtained in monkeys. 
 
 Experiment 6. — Original virus No. 11 injected into six rabbits, three 
 intraperitoneal and three intracerebral. A 5 per cent, emulsion, which had 
 been allowed to stand for a time in order to separate the larger particles, 
 was used; the dose was '2 c.c. for intracerebral, and 3 c.c. for intraperitoneal 
 injection. All the rabbits remained well, while monkeys (a), (b) and No. 11 
 died with typical paralysis [cf. p. 41). 
 
 Experiment 7. — A 20 per cent, emulsion of original virus No. 12 was 
 used. Six rabbits received injections : two intracerebral ('2 c.c), two intra- 
 peritoneal <3'5 c.c), and two intravenous (2 c.c. of emulsion filtered through 
 paper). One rabbit which received an intracerebral injection died of pleuro- 
 pneumonia on the twenty-third day ; one of the intravenous cases died on 
 the sixteenth day of some unknown cause ; the brain and spinal cord of this 
 animal showed no pathological changes (another rabbit which had received 
 no injection happened to die on the same day, and in this animal also we 
 failed to find any cause of death). The rest of the rabbits remained well. 
 Monkeys Nos. 4 and 13, infected with this emulsion, died with typical 
 poliomyelitis. 
 
 Xo injection, therefore, was successful in which virus obtained 
 direct from human beings was used. In the following cases virus 
 was used which had been passed through monkeys. 
 
 Experiment 8. — With an emulsion of virus No. 11, passed through one 
 monkey, injections were made into eight rabbits on December 17; four 
 intraperitoneal (4 c.c), four intracerebral ('2 c.c). One of the latter died 
 on the twenty-first day from pleuropneumonia. All the rest remained well. 
 Monkeys Nos. 14 and 5 became ill on the ninth and seventh day, and died 
 with typical paralysis on the third and fourth day later. Typical -post- 
 mortem changes (cf. pp. 48 and 155). 
 
 Experiment q. — On December 24 six rabbits were injected with an 
 emulsion of virus No. 11, passed through two monkeys; three injections 
 were intravenous (2 c.c. of emulsion filtered through paper), and three 
 intracerebral ('2 c.c). All remained well. Monkey No. 15, injected on the 
 same day, became ill on the eighth day, and died of paralysis two days later. 
 Typical changes -post-mortem. 
 
ETIOLOGY OF THE DISEASE 73 
 
 Experiment 10. — On December 28, 1909, five rabbits received an intra- 
 cerebral injection ('2 c.c.) of a 5 per cent, emulsion of virus Xo. 11, passed 
 through two monkeys. The animals remained well. Monkey Xo. 16 was 
 injected with the same emulsion; it became paralysed on the sixth day, and 
 died on January 5, 1910. Post-mortem appearances typical. 
 
 It is necessary for me to discuss these results more fully than I have 
 done so far, because Krause and Meinicke have stated, in the Deutsche 
 med. Wochensch?-., 19 10, 14/15, that they are justified in not considering 
 my experiments to be unobjectionable repetitions of their own; in another 
 place these authors say their results cannot be interpreted otherwise than 
 in their own sense unless " unobjectionable repetitions " of the experiments 
 lead to different results. In my opinion no objection can be brought against 
 my own experiments. Krause and Meinicke seem to imagine that the experi- 
 ments on rabbits reported in my first paper formed the basis of my state- 
 ment that ■• the Krause-Meinicke experiments allow of an interpretation 
 other than that given by the authors."' But in my second paper, the one 
 attacked by Krause and Meinicke, it will be seen that I injected the virus 
 of three cases of human poliomyelitis and of five cases of experimental 
 poliomyelitis in monkeys into rabbits without any positive result; the virus 
 from all these cases, injected into monkeys, immediately caused disease 
 and death. These are the experiments I have described in full above ; 
 in my second paper, owing to the entirely negative character of the results, 
 I did not feel justified in burdening the reader with the full details. In 
 their first paper Krause and Meinicke made the general statement that 
 rabbits are susceptible to the virus of poliomyelitis, without specifying 
 any conditions as to age or variety of the rabbits used. If they object 
 to my experiments on this score it can be only because they overlook the 
 fact that they set up such standards at a later date. There is only one 
 point to which perhaps I have not given sufficient attention and which might 
 make the criticism of Krause and Meinicke justifiable. In their first paper 
 they state that ' : very large doses were used."' Unfortunately, no indication 
 is given as to what doses they regard as being i: very large."' Later they 
 rejected the intracerebral method of injection because it did not allow of 
 large doses being administered ; but the reports in their first paper con- 
 tradict the necessity for this course, because in them they state that they 
 succeeded in infecting rabbits by just this method. 
 
 Results obtained by other Observers. — Very competent 
 observers, such as Flexner and Lewis, Leiner and v. Wiesner. 
 Landsteiner and Levaditi, have obtained entirely negative results 
 with virus which promptly produced paralysis in monkeys. At a 
 later date Eichelberg", Selter, and Potpeschnigg all failed to produce 
 the disease by injection of lumbar puncture fluid. However, 
 Krause and Meinicke make the further accusation against me, that 
 I have not paid enough attention to the reports of positive results; 
 they quote in this connection the experiments of Bonhoff, Beneke, 
 and Dahm. 
 
 Bonhoff reported that three rabbits died twenty-two days after inocu- 
 lation with material from a case of human poliomyelitis, but that none of 
 them showed any microscopical lesions characteristic of poliomyelitis, nor 
 did material obtained from the brain, spinal cord, and spleen of these 
 animals affect other rabbits in any way. He concludes : " I cannot trace 
 
74 EPIDEMIC INFANTILE PARALYSIS 
 
 the cause of death in these animals. They were well nourished, and suffered 
 from no injuries. I agree with my colleague, Romer, that no symptoms 
 such as those described by Krause and Meinicke appeared in our animals; 
 in particular, no paralysis occurred." I do not think that this statement 
 by Bonhoff contained anything which could justly cause me to change my 
 opinion of the results obtained by Krause and Meinicke. The experiments 
 of Beneke would have been more likely to do so. He injected three rabbits 
 with material containing the virus of poliomyelitis, and observed peculiar 
 symptoms ending in the death of the animals ; but the spinal cords were 
 found to be free from any demonstrable pathological change. Considering 
 that I used the same material as Bonhoff and Beneke for an extensive series 
 of experiments on monkeys and rabbits, and that I did not observe the 
 death of one single rabbit in circumstances which were in any way sus- 
 picious, I was unable to accept the observations of Beneke and Bonhoff as 
 in any way proving that rabbits were susceptible to the virus of poliomyelitis. 
 I may add that these authors themselves do not agree that their results can 
 be considered to constitute a proof of the transmissibility of the disease to 
 rabbits, as Krause and Meinicke have tried to make out. 
 
 The observations of Dahm are of but little value, as they do not include 
 any microscopical examination of the material. 
 
 In the same papers Krause and Meinicke quote Kraus and 
 Levaditi in support of their argument. They state that the experi- 
 ments of the latter constitute a " confirmation and completion " of 
 their own. 
 
 Kraus at first was unable to obtain any positive result with intra- 
 cerebral injection of pm. virus into rabbits ; later, he saw one animal die 
 with symptoms like those of rabies; the medulla and brain of this rabbit 
 injected, into other young rabbits produced symptoms of disease. He draws 
 the conclusion that " these experiments, which will be carried further, show 
 that transmission of the disease to young rabbits is possible." Krause accen- 
 tuates the fact that " the lesions characteristic of poliomyelitis were not 
 found in these animals." Later, Krause again became very sceptical about 
 the value to be attached to experiments with rabbits. At the meeting of 
 the Freien Vereinigung fur Mikrobiologie, held in Berlin in 1910, he stated 
 that all attempts to transmit the disease from the "infected" rabbits to 
 monkeys had failed. He again called attention to the fact that the result 
 of microscopical examination was entirely negative, and said that the whole 
 question of the transmission of the disease to rabbits was not proven, and 
 that all apparently successful inoculations should be received with 
 scepticism. 
 
 The experiments of Landsteiner and Levaditi can be accepted still less 
 as constituting a " confirmation and completion " of those of Krause and 
 Meinicke. The former report that in all attempts save one they failed to 
 obtain any result ; this particular rabbit received an intracerebral injection 
 on December 2Q, igog, of virus which had been passed through a monkey; 
 twenty-four days later the animal died without showing any signs of 
 paralysis. On microscopical examination appearances were seen which 
 were similar to those observed in human poliomyelitis. The perivascular 
 infiltration, so typical in human and monkey poliomyelitis, was but little 
 marked. Landsteiner and Levaditi give it as their opinion that in this one 
 case there was an affection of the central nervous system, similar to that 
 observed in poliomyelitis in man and the monkey. How far removed they 
 
ETIOLOGY OF THE DISEASE 75 
 
 were from admitting that rabbits are suitable subjects for the investigation 
 of poliomyelitis, or that the experiments of Krause and Meinicke are of any 
 value in proving this, is shown by the exhaustive criticism to which they 
 subject this theory in their latest work (November, iqio). We shall return 
 to this matter later. Landsteiner and Levaditi say cautiously that the trans- 
 mission appears to have been successful in this case. But the proof is by no 
 means complete, as no successful inoculations into other animals, specially 
 monkeys, were made from this case. I suggest further, in view of the fact 
 that this case of Landsteiner and Levaditi is the only one in which lesions 
 in any way resembling poliomyelitis have been seen, that it is not impos- 
 sible that they were due to a spontaneous disease in the rabbit and not to 
 the experimental inoculation. Joest and Degen have proved the existence 
 of the epidemic Borna's disease in horses, and it is quite possible that a 
 similar disease occurs in rabbits. 
 
 So far, none of the results obtained by other authors can be 
 regarded as confirming' those recorded by Krause and Meinicke. 
 The experiments made by Lentz and Huntemuller at the Institute 
 for Infectious Diseases in Berlin are more to the point. 
 
 Lentz and Huntemuller received from Krause and Meinicke in Hagen 
 rabbits and monkeys which had been inoculated with the cerebrospinal 
 fluid, brain and spinal cord, spleen and blood of patients who had died of 
 infantile paralysis. They report that most of the rabbits died after a shorter 
 or longer period, generally seven to eleven days, but sometimes two 
 months (!) afterwards; rabbits and monkeys were inoculated successfully 
 with various organs from these animals. Lentz and Huntemuller believe 
 that the symptoms were due to the poliomyelitis virus received in Hagen. 
 Krause and Meinicke, in their most recent paper, formulate the conditions 
 under which a successful result with rabbits may be expected. These are :■ — 
 
 (i) Only particular varieties of rabbits must be used; Krause and 
 Meinicke describe these more closely. 
 
 (2) Only young rabbits of not excessive body weight are susceptible. 
 
 (3) Only rabbits which have received " large doses " show signs of the 
 disease. (Unfortunately, in this their latest paper these authors omit to 
 state what they mean by " large doses." If this point is really of so much 
 importance, it is essential in our opinion that some data should be given 
 respecting the weight of fluid, blood, or emulsion used.) 
 
 Renewed Repetition of the Experiments. — In view of the new 
 conditions laid down by Krause and Meinicke, and of the results 
 obtained by Lentz and Huntemuller, I felt that a new situation 
 had arisen. In collaboration with Joseph I carried out a new series 
 of experiments in order to settle the question of the utility of 
 rabbits in this field of research. 
 
 As the criticism of Krause and Meinicke was directed solely against 
 myself, I asked Dr. Joseph to form his judgment as to the suitability of the 
 rabbit for experiment quite independently ; in this way I hoped to obtain 
 an unbiased opinion. Dr. Joseph made the following experiments inde- 
 pendently of me; we also observed the animals apart from one another. 
 The conditions under which the experiments were carried out were those 
 described as the most favourable by Krause and Meinicke : Belgian giant- 
 rabbits of unobjectionable, well-attested pedigree, chosen by an experienced 
 breeder of rabbits, were used exclusively; only young animals were 
 
76 EPIDEMIC INFANTILE PARALYSIS 
 
 employed which we had watched growing up ourselves ; the weight of the 
 animals used varied from 400 gm. to 710 gm., an average of 600 gm. ; the 
 method of inoculation was that recommended by Krause and Meinicke as the 
 most certain, viz. : simultaneous intraperitoneal and intravenous injection. 
 Contrary to Krause and Meinicke, we made an attempt to measure the dose 
 given ; it was weighed in the moist state before injection. The material 
 used was an emulsion of the brain and spinal cord of a monkey which had 
 died of typical poliomyelitis. 
 
 Experiment 11, April 27, 1910. — The virus used was an emulsion of the 
 brain and spinal cord of monkey 42 (virus No. 12 passed through four 
 monkeys). Four Belgian giant-rabbits (946, 947, 948, and 949) weighing 
 from 460 gm. to 630 gm. each received 2 c.c. of 5 per cent, emulsion 
 filtered through paper intravenously, and 3 c.c. of the same emulsion un- 
 filtered into the peritoneum. On the same day monkey 49 [Macacus rhesus) 
 received an intracerebral injection of '6 c.c. of the same virus. 
 
 Result : Monkey 49 well until May 9. On the 10th paresis of the hind 
 limbs, right more than left ; this became worse during the next days. 
 Improvement began on the 13th, but there was well-marked paralysis for a 
 long time. Later the animal got quite well. 
 
 Rabbits 946, 947 and 948 remained well for four months, during which 
 time they were observed daily. Rabbit 949 became paralysed in the left 
 fore limb and left hind limb on May 14; the paralysis varied in degree 
 and was permanent. It affected only the limbs of the left side, and was 
 definitely spastic in character, e.g., the left hind limb can scarcely be bent 
 at all. The animal was killed on June 21 for purposes of diagnosis. 
 Macroscopic investigation was negative. 
 
 Dr. Joseph took the trouble to make serial sections of the spinal cord 
 and of pieces of the medulla and brain. No lesions characteristic of polio- 
 myelitis could be found in this animal. Unfortunately, he did not succeed 
 in finding any cause for the paralysis. We have never observed a spastic 
 hemiplegia in monkeys, nor has Wickman throughout his wide experience 
 in man, and it is probably not incorrect to assume that the paralysis in this 
 rabbit was not due to the injection, or, at any rate, was not the result of 
 infection with poliomyelitis. I may mention here that paralysis is observed 
 very frequently in rabbits kept in hutches in the laboratory, and that the 
 cause cannot be found always. 
 
 Experiment 12, May 19, 1910. — An emulsion of the brain and spinal 
 cord of monkey 48 (virus No. 11, passed through six monkeys) was used. 
 Rabbits 943, 944, 945, 950, 951, and 952 received an intravenous injection 
 of 2 c.c. of a 5 per cent, emulsion filtered through paper, also an intra- 
 peritoneal injection of 3 c.c. of the same virus unfiltered. Monkey 56 
 received '8 c.c. of the emulsion into the brain and 3 c.c. into the peritoneum. 
 
 All the rabbits remained perfectly well, without a trace of paralysis, 
 during four months under daily observation. 
 
 Monkey 56 remained well until June 1. On June 2 in the morning 
 paresis of the fore limbs ; in the afternoon definite paresis t»f the hind limbs ; 
 June 3 paresis more marked; June 4 total paralysis of the left hind limb 
 and of the right fore limb, marked paresis of the other limbs; June 5-7, 
 condition unchanged; June 8, marked general paralysis. Found dead on 
 the 10th. Typical microscopical appearances. 
 
ETIOLOGY OF THE DISEASE 77 
 
 Experiment 13, May 31, 1910. — An emulsion of the brain and spinal 
 cord of monkey 36 (virus No. 11 passed through five monkeys) was used. 
 
 Inoculation was carried out with rabbits 953, 954, 956, 957, 958, 959, 960, 
 961, 962, 963, and with monkey 58. The rabbits received an intraperitoneal 
 injection of 2 c.c. of a 5 per cent, filtered emulsion and an intravenous 
 injection of 3 c.c. unfiltered emulsion. Monkey 58 received '5 c.c. of filtered 
 virus into the brain. 
 
 All the rabbits remained well for four months under daily observation. 
 
 Monkey 58 remained well until June 10. On the nth total paralysis 
 of the left hind limb and paresis of the right hind limb. On the 12th total 
 paralysis of both hind limbs and paresis of both fore limbs. On the 13th 
 general paralysis and death. Microscopical appearances very typical and 
 very intense in the lumbar region. 
 
 Experiment 14, July 13, 1910. — The virus used was an emulsion of the 
 brain and cord of monkey 48 (Virus No. n passed through six monkeys). 
 Rabbits 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, and monkey 102 were 
 inoculated. The rabbits received an intravenous injection of 2 c.c. of a 
 5 per cent, emulsion filtered through paper, and an intraperitoneal injection 
 of 3 c.c. of the s per cent, emulsion unfiltered. 
 
 All the rabbits remained well for four months under daily observation. 
 
 Monkey 102 received an intracerebral injection of '6 c.c. of 5 per cent, 
 emulsion, unfiltered. Well until the 24th. On the 25th typical flaccid 
 paresis of the hind limbs and weakness of the back muscles. In the even- 
 ing paralysis of the hind limbs and of the left fore limb, facial palsy on 
 the right side. Death on the 25th. Microscopical appearances typical. 
 
 Thirty-one rabbits in four series received large doses of 
 material containing the virus of poliomyelitis by simultaneous 
 intravenous and intraperitoneal injection. The virulence of the 
 material used was proved by the fate of the four control monkeys, 
 which all died of typical poliomyelitis. Of the thirty-one rabbits, 
 thirty remained well for four months under daily observation; one 
 single animal suffered from an atypical form of paralysis for which 
 no lesion of the nature of poliomyelitis could be made responsible. 
 
 This closes the series of our experiments with rabbits. In all, 
 including the earlier experiments, there were eighty-one animals; 
 of these, one died from suppuration following a bite, two died of 
 pleuropneumonia, one of a cause unknown, and one of a form of 
 paralysis not due to poliomyelitis, but the cause of which could 
 not be elucidated. All the rest remained well. 
 
 Even when we conformed to all the conditions laid down by 
 Krause and Meinicke, we were unable to corroborate their results. 
 Our observations form a complete contrast to those obtained by 
 Krause and Meinicke, as also by Lentz and Huntemiiller. As I 
 do not believe that the matter can be carried any further by means 
 of experiment, I will attempt to do so by a critical discussion of 
 the facts. 
 
 Criticism of the Arguments in Favour of using Rabbits. — 
 Krause and Meinicke base their view, that the rabbit is a suitable 
 
78 EPIDEMIC INFANTILE PARALYSIS 
 
 animal for experiments with poliomyelitis and that their results 
 prove this, upon the following" arguments : They emphasize the 
 facts (1) that rabbits inoculated at the same time become ill at the 
 same time and some time after the infection; (2) that, consequently, 
 the symptoms observed cannot be due directly to injury received 
 at the time of injection, owing to material from another animal 
 being introduced into the blood; (3) that the symptoms observed 
 were certainly "nervous in character." This argument is not 
 quite sound; I refer the reader to the full description of my earlier 
 experiments (pp. 30-31); there he will find that the introduction 
 of morbid material of various kinds (streptococci, B. coll) in fact 
 of any foreign substance in a molecular state directly into the 
 blood-stream, will cause paralysis or symptoms similar to paralysis 
 at a time considerably later than the date of injection. 
 
 Lately Selter has again found that infection of rabbits with 
 streptococci causes paralysis. In this connection the researches of 
 Potpeschnigg are even more instructive. He obtained a diplo- 
 coccus from the cerebrospinal fluid of a case of poliomyelitis, and 
 injected living and dead cultures of this organism into the peri- 
 toneum, veins, and brains of rabbits. "In a few cases widespread 
 paralysis resulted." This author was prevented from drawing a 
 wrong conclusion from his results by a knowledge of previous 
 experiments with rabbits (cf. p. 31). In view of the present dis- 
 cussion I recommend the reader to refer again to these experiments. 
 
 In addition, Lentz and Huntemuller, who believe that they 
 have confirmed the results obtained by Krause and Meinicke, have 
 stated : " We would not lay much stress upon convulsions and 
 paralysis occurring in rabbits; we have observed rabbits which died 
 of convulsions soon after being brought to the department and 
 by inoculation from these animals zve have occasionally been able 
 to produce convulsions in others."* 
 
 Meinicke's further argument, that no other cause of death was 
 ascertainable, is of very little value; how often do we not have 
 to put a query under the heading " Cause of death," in the case 
 of rabbits which die in the laboratory? One of the best arguments 
 in support of their contention would have been the demonstration 
 that the lesions produced in their rabbits were similar to the lesions 
 of poliomyelitis in man or monkey. Indeed, In the course of a 
 lecture before the Rheinisch-Westfalischen Gesellschaft fur innere 
 Medizin und Nervenheilkunde, on November 14, 1909, Meinicke 
 said: "Together with Dr. Holm, of Essen, we were able to 
 demonstrate qualitatively the same changes in one of our rabbits, 
 which died with characteristic symptoms, as are found in typical 
 cases of poliomyelitis in man and in monkeys. Vascular and diffuse 
 cell infiltrations and small haemorrhages were found in the grey 
 matter of the spinal cord and degenerative change in the tigroid 
 of the ganglion cells." In another place he says: "It may be 
 mentioned here that we found characteristic changes (thrombosis, 
 
 * No italics in the original. 
 
ETIOLOGY OF THE DISEASE 79 
 
 nsemorrhage, diffuse and perivascular cell infiltration) in the central 
 nervous system of animals inoculated from these rabbits." Finally, 
 he said: "Thus the final proof is provided; we were justified in 
 interpreting" our results with rabbits as a true transmission of the 
 virus of infantile paralysis.'"' 
 
 But the experiments of Lentz and Huntemuller, which he him- 
 self quotes in support of his argument, are not in keeping" with 
 this generalization. These authors write : " Microscopical evid- 
 ence of any lesion is frequently very slight, but congestion of the 
 vessels, haemorrhages and cell degeneration are often to be found 
 in the grey matter, particularly of the brain. We were unable to 
 find any cell infiltration round the vessels or in the substance of 
 the central nervous system such as is found in cases of poliomyelitis 
 in man and in monkeys."* 
 
 Lentz and Huntemuller make a definite statement, therefore, 
 that they did not find perivascular infiltration as was observed by 
 Meinicke. But we shall see later that perivascular infiltration is 
 the most characteristic change in poliomyelitis. With regard to 
 the findings of Lentz and Huntemuller, I must call attention again 
 to the results of the earlier experiments in which not only bacteria 
 of all kinds but also non-living material was used. The changes 
 described by the former experimenters remind one forcibly of those 
 found by Lentz and Huntemuller. Personally, I found myself un- 
 able to agree that their specimens, which were demonstrated at a 
 meeting of the Freien Vereinigung fiir Mikrobiologie, showed the 
 presence of the lesions of poliomyelitis. Landsteiner said of these 
 specimens: "The preparations from rabbits which have been 
 demonstrated show very slight changes; in the sections of the 
 spinal cord of a monkey inoculated with material from a rabbit 
 by Lentz and Huntemuller there are none of those characteristic 
 changes which are always found in monkeys, and I do not think that 
 a diagnosis of poliomyelitis should be made, nor do I think it a 
 probable diagnosis. I have seen similar appearances in animals 
 which certainly did not die of poliomyelitis." 
 
 As there can be no doubt that the monkey is susceptible to 
 the virus of poliomyelitis, and as the disease can be reproduced 
 in monkeys in a form both clinically and pathologically similar to 
 the disease in man, the question whether the rabbits of Krause and 
 Meinicke and of Lentz and Huntemuller really died of the effects 
 of poliomyelitis virus allows of a crucial experiment. If the rabbits 
 died of poliomyelitis, inoculation of a monkey with material obtained 
 from them should produce the typical clinical and pathological 
 picture of poliomyelitis in the susceptible monkey. Krause and 
 Meinicke claim to have carried out this experiment and Lentz and 
 Huntemuller in Berlin set up the same claim. We will consider 
 these claims more closely. 
 
 I have collected the allegedly convincing experiments from Meinicke's 
 papers, and arranged them in the form of a genealogy. 
 
 * No italics in the original. 
 
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 EPIDEMIC INFANTILE PARALYSIS 
 
 
 
 
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ETIOLOGY OF THE DISEASE 8 1 
 
 We must confess to having" many doubts as to the validity 
 of the proof put forward. In the first place, it is remarkable 
 that lumbar puncture fluid should be the original virus-containing 
 material, and that at a date several days after the beginning of 
 the paralysis. As we shall see later, in no single instance has it 
 been found possible to infect monkeys with human cerebrospinal 
 fluid. It would be very remarkable if such material had affected 
 a rabbit, which is at least less susceptible than a monkey. Further, 
 the first rabbits only became ill after thirty-five days (the one 
 which was sent to Berlin only after fifty days), while the subsequent 
 rabbits (275-278) died in four to five days. I can hardly believe 
 that the fact that these animals were younger can account for such 
 a difference in incubation period. The symptoms observed in the 
 monkeys were not in any way typical of poliomyelitis. I must 
 refer the reader to Meinicke's original publication on this point; he 
 says himself that he did not observe any marked paralysis in the 
 monkeys.* 
 
 Landsteiner says of the observations made by Meinicke : " It 
 is quite uncertain from what disease these monkeys suffered.'' In 
 another place, in conjunction with Levaditi, he says: " Elles sont 
 peu nettes et ne sauraient etre idendifiees a celles que Ton releve 
 ordinairement chez l'homme, ou les simiens infectes avec du virus 
 de passage." 
 
 The Berlin experiments quoted by Krause and Meinicke show clearly 
 that these authors accept a small amount of evidence as proof that polio- 
 myelitis has been transmitted to monkeys. In these experiments the blood 
 of a monkey alleged to be suffering from poliomyelitis was said to have 
 caused abortive poliomyelitis. One of the monkeys inoculated showed 
 " transient nervous symptoms " after a week had elapsed, and Krause and 
 Meinicke actually say that " this experiment gives valuable support to our 
 own inoculations with the blood of rabbits and human beings." 
 
 How little the symptoms observed in Meinicke's monkeys had to do 
 with poliomyelitis is shown further by the observation made by him, that 
 acutely and severely paralysed cases were able to overcome the paralysis 
 occasionally, when they were stimulated to perform movements and were 
 subjected to radiant heat. Such an observation has never been made by 
 any other investigator of poliomyelitis. When Meinicke goes so far as to 
 explain the atypical character of the disease produced by suggesting that 
 the action of the virus on monkeys has been altered by its passage through 
 rabbits he is ignoring the -petitio -princifiii. 
 
 * He certainly continues : " On further careful study of the results 
 reported by Romer, I have received the impression that they more or less 
 correspond with symptoms observed in my monkeys." But I must object 
 strongly to the view that the symptoms observed by me bore the remotest 
 resemblance to those described by Meinicke. I hope that the full report 
 of the symptoms which I have given above will enable the reader to form 
 his own judgment. Let him compare them with those described by Meinicke 
 in the Deutsche med. Wochenschrift, 1910, 15, and see whether the latter 
 bear any resemblance to the symptoms I have described, and which Meinicke 
 himself demonstrated by means of the cinematograph at the Medical 
 Congress at Wiesbaden in 1910. 
 
82 EPIDEMIC INFANTILE PARALYSIS 
 
 In the Berlin experiments of Lentz and Huntemuller, which are quoted 
 as confirmatory, monkeys inoculated with human cerebrospinal fluid died 
 seven to eleven days after infection " without having shown any signs of 
 paralysis." " Pathological, microscopical, and bacteriological examination 
 proved negative." The transmission of the disease from rabbits, sent from 
 Hagen to Berlin, to monkeys was successful. The monkeys showed 
 " repeated short periods of paralysis at intervals of two to four weeks." 
 Another monkey " died of marasmus following two attacks, from which 
 it had recovered partially." Yet another was " killed during an attack." 
 In these monkeys were found " marked engorgement of the vessels, 
 haemorrhages, degeneration of the ganglion cells, which were invaded by 
 small cell infiltration," i.e., no adventitial or perivascular infiltration, the 
 characteristic lesion of the disease. 
 
 It is clear that in these experiments neither true paralysis nor 
 characteristic microscopical lesions were observed. Lentz and 
 Huntemuller assume that the virus was attenuated in order to 
 explain this. The difference between my results and those of the 
 Hagen and Berlin investigators cannot be bridged. I found that 
 material which was fully virulent in monkeys was non-virulent in 
 rabbits, and yet in Hagen and Berlin material which was feebly 
 virulent or non-virulent for monkeys was virulent for rabbits The 
 question of a biological change having taken place in the virus might 
 have been considered if I and other writers had not obtained similar 
 results by using virus taken direct from human beings. The fact 
 that Lentz and Huntemuller were able to infect rabbits easily with 
 virus sent to them by Landsteiner from Vienna and by me from 
 Marburg, while we found the same virus entirely non-virulent for 
 rabbits, still remains to be cleared up. I shall return to the question 
 of how these contradictions may be explained. 
 
 So far, the results of a critical analysis prove that Krause and 
 Meinicke are not justified in claiming that their results prove that 
 rabbits are susceptible to the virus of poliomyelitis and, therefore, 
 that they are suitable animals for research, nor that they had suc- 
 ceeded in transmitting the disease to rabbits. A number of im- 
 portant considerations still remain. 
 
 Further Objections to Experiments with Rabbits. — To begin 
 with, it is remarkable that the intracerebral method should have 
 proved less efficacious than the intraperitoneal and intravenous 
 methods. Experiments with monkeys have proved the intracerebral 
 method to be the most certain. Considering the selective affinity 
 -of the virus to the central nervous system, it is difficult to under- 
 stand why bringing virus and the central nervous system directly 
 together should have given such poor results. Further, it is really 
 extraordinary that, besides the brain and spinal cord, the lumbar 
 puncture fluid, the spleen pulp, and the blood of-human beings, and 
 the liver of a monkey should all prove to contain the virus. Even 
 by using the very susceptible monkey, no other experimenter has 
 succeeded in demonstrating the virus in this material. I myself had 
 consistently negative results when using blood and cerebrospinal 
 
ETIOLOGY OF THE DISEASE 83 
 
 fluid direct from man to monkey, and Flexner and Lewis, Leiner 
 and v. Wiesner, Landsteiner and Levaditi have all had the same 
 experience. Selter and Potpeschnigg injected cerebrospinal fluid 
 without result. Only Flexner and Lewis have been able to find 
 virus in the blood and cerebrospinal fluid of monkeys, and then only 
 by using enormous quantities of blood and under special conditions 
 with cerebrospinal fluid (intracerebral injection of the monkey with 
 removal of the cerebrospinal fluid before the occurrence of para- 
 lysis). 
 
 The experience of Lentz and Huntemuller relative to the 
 resistance of the virus to glycerine is totally different to my own. 
 They state that preservation in 50 per cent, glycerine diminishes 
 the virulence; that they succeeded in inoculating" only one out of 
 four monkeys with the virus which I sent to them does not alter the 
 fact that in my experiments the glycerine virus was transmitted 
 readily from monkey to monkey, and led to a typical illness in 90 
 per cent, of the cases. 
 
 Bearing in mind all the objections, the uncertainty of the 
 clinical symptoms and the absence of any typical microscopical 
 change, one can only be very surprised that Krause and Meinicke 
 believe that their opinion, that the inoculation with material con- 
 taining pm. virus was the cause of death in their rabbits, " has been 
 confirmed in all directions." 
 
 To recapitulate : the following facts justify the scepticism with 
 which numerous authors have looked upon rabbits as subjects for 
 experimental poliomyelitis and have regarded the interpretation 
 which Krause and Meinicke have placed upon their results. The 
 symptoms observed in rabbits are of no value. The alleged positive 
 results were obtained with material which was proved not to con- 
 tain the virus in an infective condition, because it failed to produce 
 poliomyelitis even in such a sensitive animal as the monkey. The 
 experimentum cruris must be considered to have failed since reinfec- 
 tion from the rabbit back to the monkey did not produce poliomye- 
 litis in the latter. The histological lesions found in the rabbits 
 correspond to lesions which are easily produced whenever any 
 foreign material is injected into rabbits, and they are quite different 
 to the lesions of poliomyelitis. The alleged positive results 
 obtained by Krause and Meinicke, Lentz and Huntemuller are 
 opposed by the at least equally numerous negative results obtained 
 by a larger number of observers, who worked with highly virulent 
 material and in part under the optimum conditions as formulated 
 by Krause and Meinicke. No support is given by any investigations 
 along the lines of serum-diagnosis {vide infra). 
 
 An Attempt to explain the Difference. — It is naturally very 
 difficult to elucidate the cause of death in the rabbits observed by 
 Krause and Meinicke and Lentz and Huntemuller. The following 
 is a possible explanation : It is possible that the animals suffered 
 from some other disease, which was inoculable from one to the 
 other and was carried by a non-bacterial virus. The difference 
 
84 EPIDEMIC INFANTILE PARALYSIS 
 
 between the results obtained by Lentz and Huntemiiller on the one 
 hand, and Joseph and myself on the other, using the same virus, 
 would seem to point to this. In Berlin the virus from Marburg 
 produced the same results in rabbits as that from Hagen; in our 
 hands, under the most favourable conditions and with rabbits which 
 were said to be of the most susceptible variety, the virus proved 
 itself innocuous to rabbits. One sentence in the paper by Lentz 
 and Huntemiiller is also significant; they say that rabbits which 
 had not been injected and had only just arrived at the laboratory 
 sometimes suffered from convulsions, and that inoculations made 
 from these animals into others caused convulsions. We cannot say 
 if this explanation is the true one, and I agree with the position 
 taken up by Landsteiner and Levaditi : " que les divergences doivent 
 dependre de quelques circonstances encore mal definies a l'heure 
 actuelle." 
 
 Practical Conclusions. — Krause and Meinicke, by making 
 claims to which they have no right, make it necessary that the whole 
 position of the rabbit should be clearly defined even at the risk of 
 fatiguing the reader. Krause and Meinicke make no less a claim 
 than this: "That these experiments prove for the first time that 
 acute epidemic infantile paralysis is a communicable disease." In 
 another place: " The proof, furnished by us for the first time, that 
 the virus of poliomyelitis can be cultivated for a considerable time 
 within the bodies of animals has made it possible to determine the 
 nature of the virus more exactly, to test the efficacy of therapeutic 
 measures by means of experiments with animals, and, above all, to 
 study the question of immunity in animals." They claim further 
 that they are the first to demonstrate the capacity of the virus to 
 pass through a filter. I hope that I have proved conclusively that 
 there is no justification for such claims. 
 
 A more important reason than this question of priority arises 
 from the nature of the practical deductions drawn by Krause and 
 Meinicke. In our opinion they are not justified. They recom- 
 mend the rabbit for testing for the presence of poliomyelitis virus 
 in faeces, in urine, in mucus from the throat, and in articles of 
 food. They advise inoculation into rabbits for diagnostic purposes 
 in doubtful cases, even in the abortive type of poliomyelitis. They 
 hope to arrive at a diagnosis by injecting the blood of a doubtful 
 case during life into a rabbit. A grave practical danger is present 
 in these recommendations; the rabbit is so sensitive to all kinds 
 of trauma and disease, and reliable criteria, by which a positive 
 result may be judged, are so few that serious mistakes are inevit- 
 able. 
 
 One more assertion by Krause and Meinjcke requires correc- 
 tion. They say: "A comparison of our results with rabbits and 
 those obtained by other writers with monkeys seems to show that 
 the rabbit is at least as susceptible as the monkey, and perhaps 
 more so." In another place they speak of " the relatively great 
 susceptibility of the rabbit," in which " relative " can apply only 
 
ETIOLOGY OF THE DISEASE 85 
 
 to the monkey, the only other animal which enters into the question. 
 The facts are the following" : 90 to 95 per cent, of monkeys which 
 receive an intracerebral injection of the virus become affected with 
 poliomyelitis, and most of them die of the disease; in my own 
 experience and that of most other authors not one single rabbit 
 contracted poliomyelitis, and a critical examination of alleged posi- 
 tive results makes it clear, that at any rate it is very improbable 
 that the symptoms observed can be connected with the virus in any 
 way. 
 
 On one point one can agree with Krause and Meinicke. They 
 point out that monkeys are not suitable for the study of conditions 
 of immunity, because large series of these animals are not possible 
 for obvious reasons. Unfortunately a knowledge of this fact does 
 not render other unsuitable animals any more suitable for the 
 purpose. 
 
 Krause and Meinicke have underestimated the importance of 
 the experiments made with monkeys; they clearly do not realize 
 how susceptible the monkey is and how typical are the clinical and 
 pathological features which are produced. The number of experi- 
 ments which can be carried out with monkeys by each individual 
 investigator must remain small; but when we are in a position, as 
 at the present time, to collect the results of experiments performed 
 all over the world (New York, Paris, Vienna, Marburg), results 
 may be obtained, as we have seen already and shall see later, which 
 are of the greatest importance to science. With rabbits the most 
 experienced investigators — Flexner and LeAvis, Landsteiner and 
 Levaditi, Leiner and v. Wiesner, and many others — have obtained 
 only the most dubious results. 
 
 So far the rabbit has not proved to be a suitable animal for the 
 investigation of poliomyelitis. 
 
 [Since Professor Romer thus defined the position of the rabbit 
 as an animal for experiment, the American investigator, H. K. 
 Marks, has carried out further experiments. Using virus obtained 
 from the brain and spinal cord of a monkey affected with poliomye- 
 litis he made intravenous and intraperitoneal injections into rabbits; 
 the animals died on the eighth to fifteenth day with convulsions. 
 Post-mortem examination revealed no lesions, but the disease was 
 able to be transmitted to further rabbits by injection of the brain and 
 spinal cord in most cases, and sometimes by using the liver and 
 spleen. Marks was unable to carry the disease through more than 
 six rabbits in this manner. From the second, fourth, and sixth - 
 rabbit-passages, however, he was able to produce typical lesions of 
 poliomyelitis in three monkeys by intracerebral inoculation with the 
 brain and spinal cord of the respective rabbits. Marks says 
 definitely that in the rabbits " the disease cannot be recognized as 
 poliomyelitis"; further, he claims only to have demonstrated that 
 " the disease can survive and probably even be propagated in a 
 domestic animal that does not show any of the peculiar symptoms 
 
86 EPIDEMIC INFANTILE PARALYSIS 
 
 of the disease as it occurs in man." From this it is clear that his 
 experiments do not give any support to the claims made on behalf 
 of the rabbit by Krause and Meinicke. It is true that the results 
 of re-inoculation from the diseased rabbits into monkeys proved the 
 presence in them of the virus of poliomyelitis, but until the monkey 
 was employed there was no evidence that the virus of poliomyelitis 
 was present in the rabbits. The position of the rabbit thus remains 
 the same as when it was defined by Professor Romer. — Trans.] 
 
CHAPTER IV. 
 
 Pathology and Pathogenesis. 
 
 I.— HISTORICAL RETROSPECT— THE SALIENT 
 
 FEATURES. 
 
 Heine's Views. — In my opinion a retrospect of the pathology 
 of the disease should begin with a man whose name is not often 
 heard in this connection. Heine in his first monograph mentioned 
 the spinal cord as the probable seat of the lesion involved, and in 
 his second monograph he insisted upon the spinal nature of the 
 disease. In order to do full justice to Heine's clear and definite 
 statement it is necessary to remember that before him no one had 
 studied the disease in a scientific manner, and also what the condi- 
 tion of neuropathology was at that time. It is true that Heine did 
 not demonstrate the lesion which he postulated, but that does not 
 detract from the value of his discovery. He himself regretted that 
 he could produce only hypotheses and not facts in the matter of 
 the pathogenesis of the disease. The arguments by which he estab- 
 lished his thesis were so exact and so comprehensive, that I feel 
 impelled to draw attention to this portion of his services to 
 medicine. 
 
 He first excludes the brain as the seat of the disease and, by 
 a process of clear, logical criticism, arrives at the spinal cord as 
 the site of the cause of the paralysis. " Although the primary irri- 
 tative signs mentioned above do not exclude the possibility of a 
 lesion of the nerve centres, and although one cannot be sure that 
 some of the symptoms observed during the acute period are not 
 due to an irritative lesion of the brain, yet the subsequent signs 
 point rather to a lesion of the spinal cord as the essential factor in 
 producing the paralysis, without more than a transient affection of 
 the brain and its functions. The disease may consist in a sudden 
 pressure on the cord produced by capillary extravasations or other 
 exudates, which would lead to atrophy later, or there may be some 
 other kind of lesion." A contemporary statement of Bardeleben's 
 shows how much Heine's view appealed to clinicians : " Against 
 the cerebral, and in favour of the spinal localization of the lesion, 
 the following facts are of importance : the absence of lasting 
 
88 EPIDEMIC INFANTILE PARALYSIS 
 
 cerebral signs; the integrity of the organs of special sense and of 
 the intellect; finally, the rapid loss of electrical excitability in the 
 muscles. It is well known that in paralysis due to a cerebral lesion 
 the electrical excitability is maintained for years, while the spinal 
 cord in this respect behaves like a nerve, and a lesion of it causes 
 disappearance of the reaction in the muscles in two or three weeks." 
 
 Heine was undoubtedly wise in rejecting rickets, scrofula, and 
 syphilis as being of any pathogenic importance. His firmness in 
 adhering to his view of the spinal nature of the disease was of great 
 value when the celebrated French clinicians, Rilliet and Barthez, 
 published negative results from autopsies and gave the name of 
 " essential paralysis " to the disease. And again, when Bouchut 
 considered the disease to be a " paralysis idiopathica " caused by 
 cold. Bardeleben criticized the negative findings of the former two 
 authors with the words : " They are of but little value owing to the 
 exclusively macroscopical nature of the investigation." 
 
 Heine's reasons for assuming a lesion of the cord were the 
 following: The functions of the brain are not affected; the paralysis 
 succeeds the general symptoms immediately, which would not be 
 the case if the lesion were peripheral; the loss of electrical excita- 
 bility, the absence of sensory symptoms., the degree of paralysis, 
 the frequency with which the paralysis affects the lower limbs, the 
 subsequent muscular atrophy, the incurability of the paralysis are all 
 points against a peripheral localization. The occurrence of similar 
 paraplegia in lesions due to other diseases affecting the spinal cord 
 led Heine directly to a spinal localization. Finally, and this reveals 
 the born clinician in Heine, he was convinced by the appearance of 
 the helpless patients that he had to deal with a deep-seated lesion 
 of the nervous system. He drew attention especially to the grey 
 matter of the cord as " the chief channel of motor activity." With 
 a prophetic insight into the true nature of the pathogenesis he adds : 
 " Knowing all this, knowing that the grey matter is so well sup- 
 plied with blood-vessels that accidental plethora may easily cause 
 extravasations, while the grey matter is exceedingly liable to suffer 
 from variations in its nutriment, knowing that the sections show 
 atrophy of the grey matter to be the cause of the paralysis, what is 
 to hinder us from deducing the cause of the diminution of motility 
 from the same factors ? Why should we not suppose some acute 
 process to take place, which causes an alteration in the grey matter, 
 impairs its conductivity, produces the paralysis in the lower limbs, 
 and, by affecting the nutrition of the grey matter, causes secondary 
 atrophy in it?" In another place: "Although the preceding 
 anatomical facts and my experimental experience lead me to consider 
 the various types of paralysis as due to spinal lesions, and being, in 
 a way, different degrees of the same disease, I must not be under- 
 stood to set apart particular portions of the cord as the invariable 
 seat of the primary infection nor to consider any particular kind of 
 lesion as pathognomonic; in the present state of our knowledge of 
 the physiology and pathological anatomy of the part I cannot 
 
PATHOLOGY AND PATHOGENESIS Sq 
 
 make more than conjectures. Yet I cannot but give expression to 
 my firm conviction that it is not in the brain or in the peripheral 
 nerves, but in the spinal cord itself, speaking generally, that we 
 must seek the cause of infantile paralysis. Even although we 
 possessed no anatomical proof, yet the uniformity of the symptoms 
 in 150 carefully observed cases, all pointing to this organ, is of no 
 small importance; a theory based on observation of so large a 
 number of cases might even venture to fill the gaps left in our 
 knowledge of the pathology. I would ask those who are not 
 satisfied with the results of pathological research (I myself, con- 
 scious as I am of their incompleteness, cannot regard them as being 
 a final proof), whether they are able to bring forward other facts 
 in support of their own different opinions or to formulate any theory 
 which will hold as good in all the circumstances. If such people, 
 who are only too prone to give the name ' essential infantile para- 
 lysis ' to our disease, because it avoids the difficulty of specifying 
 the nature of the illness, bring to me sections which show no lesion 
 of the nerve centres, I would advise them to use the microscope ; if 
 this also fails to reveal a lesion I would suggest that, if at the 
 present time changes are not evident to our eye, it is the latter 
 which is at fault. 
 
 " Although I cannot but emphasize my conviction that it is the 
 spinal cord which is involved, yet it remains only my humble 
 opinion. I shall be quite satisfied if my statement has the practical 
 result of stimulating the interest of physicians in the disease, so that 
 the number of pathological investigations may increase and thereby 
 a definite result be attained. 
 
 " On consideration of all the factors, and with the concurrence 
 of many authors, I have adopted the name paralysis infantilis 
 spinalis for this form of paralysis; with all respect to the authority 
 of Rilliet in matters pertaining to diseases of children, I consider 
 his term ' paralysie essentielle ' which has been so widely adopted, 
 as also that of Bouchut, ' paralysis idiopathica,' to be incorrect." 
 
 It is not going too far to say that it was Heine who showed the 
 way for all subsequent research; he indicated the spinal cord as the 
 seat of the disease, and in so far he was the founder of the patho- 
 genesis of the disease. 
 
 From Heine to Charcot, Roger and Damaschino. — The post- 
 mortem reports published by Heine included some cases of paralysis 
 due to other diseases ; in one case (Longet, " Anatomie et Physiolog'ie 
 du Systeme nerveux, " Part I) there was paralytic club-foot, marked 
 atrophy of the anterior roots and the corresponding lumbar and 
 sacral nerves, but no abnormality of the spinal cord. Another case 
 (Hutin) was certainly one of old infantile paralysis; in this there 
 was an extraordinary atrophy of the spinal cord. This was the first 
 positive post-mortem, although the findings were only macroscopic. 
 
 The Frenchman Cornil (1863) made the first thorough micro- 
 scopical examination of a case (a woman, aged 49, who had suffered 
 from the effects of infantile paralysis for forty-seven years). He 
 
go EPIDEMIC INFANTILE PARALYSIS 
 
 found considerable atrophy of the ventrolateral column, particularly 
 in the dorsal and lumbar regions, amyloid bodies in the anterior 
 horns, most numerous in the vicinity of the blood-vessels. Cornil 
 passed by the most important change, although he not only observed 
 it but also described and illustrated it: "On voit une cellule ner- 
 veuse, qui est du reste la settle qui montrait cette preparation; 
 mais stir les coupes plus epaisses nous avons vu que les cellules ner- 
 veuses etaient intactes et avaient conserve leurs rapports normaux.'' 
 Cornil therefore observed the absence of ganglion cells, but did not 
 lay any stress upon it. His discovery was confirmed by Laborde in 
 1864, who examined two cases and found inflammatory connective 
 tissue in the anterior and lateral tracts, but noted that the ganglion 
 cells were " parfaitement saines." 
 
 In 1865 Prevost and Vulpian went distinctly further; they noted 
 atrophy of the anterior horns and diminution in the number of 
 ganglion cells, as well as atrophy of the anterior and lateral 
 columns. Lockhart Clark confirmed this in 1868. These authors 
 therefore observed the most important fact and described it, but 
 did not appreciate that it was the one thing by which the occurrence 
 of the paralysis could be explained. 
 
 This was reserved for a work which on that account may be 
 considered as laying the true foundation of all subsequent micro- 
 scopical pathology. Charcot and Joffroy, in 1870, made an examina- 
 tion of a woman aged 40, who had been paralysed for thirty-three 
 years; they found similar appearances as the authors mentioned 
 above, but they recognized the fundamental pathological importance 
 of the loss of the ganglion cells, and formulated the brilliant hypo- 
 thesis that the ganglion cells form a kind of trophic centre for the 
 nerves and muscles belonging to them; this theory made it possible 
 to understand the occurrence of the paralysis, and the subsequent 
 muscular atrophy. The investigations of Charcot and Joffroy are 
 important, not only because of this generally accepted neuro- 
 physiological theory, but because of the further conclusions which 
 they drew. On account of the remarkable way in which certain 
 groups of cells, markedly in the lumbar enlargement, were chiefly 
 affected, and in view of the absence of any true inflammatory or 
 haemorrhagic changes, they inferred a primary affection of the 
 ganglion cells with the production of a certain degree of secondary 
 reaction in the neighbouring interstitial tissues. 
 
 Charcot's and Joffroy 's observations were confirmed in the 
 same year by Parrot and Joffroy, who accepted the theoretical con- 
 clusions of the former. But one further discovery was made which 
 was to be of great importance for the further development of the 
 subject. In a child aged 3, one year after it had been afflicted with 
 poliomyelitis, they found blood-vessels which were more numerous, 
 thickened, and infiltrated with small round cells in situations where 
 the ganglion cells appeared normal. As, however, they found 
 ganglion cells affected in other places without any particular change 
 in the blood-vessels being present, they adhered to the theory of 
 
PATHOLOGY AND PATHOGENESIS 9 1 
 
 Charcot. In the next year (1871) Roger and Damaschino were 
 able to demonstrate marked changes in the vessels, with cell pro- 
 liferation in the anterior horns in more recent cases (i.e., after two 
 and a half, six, and thirteen months). They raised the question, 
 without giving any decisive answer, whether the process was 
 primarily parenchymatous, as Charcot believed, or primarily inter- 
 stitial. 
 
 In any case these investigations excluded the possibility that 
 the process was a purely degenerative one; it was undoubtedly an 
 inflammatory, "myelitic" process. 
 
 The Dispute over Charcot's Theory. — The discussion appears 
 at first sight to be tiresomely academic. Wickman points out that 
 it is not so, because the assumption of a primary interstitial inflam- 
 mation at once raises the difficulty as to how the "systematic" 
 character of the symptom-complex in most of the cases can be 
 explained. 
 
 (a) Investigation of Chronic Cases. — Discussion was limited at 
 first to the results obtained by examination of cases of long stand- 
 ing. Roth confirmed the findings of Roger and Damaschino, but 
 came to the conclusion that the interstitial changes were primary 
 and the degeneration of the ganglion cells secondary. Schultze in 
 1875 pointed out that frequently only isolated groups of cells were 
 affected, and he considered that this would not be possible if the 
 pathological process was primarily parenchymatous. Other oppo- 
 nents of Charcot's theory were Erb, Leyden (1875). Turner (1879), 
 Taylor (1879), Eisenlohr (1880), Archambault and Damaschino 
 (1883). who drew attention to the frequent occurrence of peri- 
 vascular cell infiltration, and conceived the whole process to be one 
 of diffuse myelitis with a tendency to greater intensity in particular 
 regions. Eisenlohr observed further that the posterior horns and 
 the white matter were also affected. Kawka (1889) proved the 
 connection between the localized lesions and the changes in the 
 vessels by means of serial sections. Jagic, Hoche. van Gehuchten, 
 Bielschowsky, and others opposed Charcot's theory as a result of 
 investigation of chronic cases. 
 
 On the other hand, supporters of Charcot appeared, Dejerine 
 (1878), Stadelmann (1883), an d. m particular, von Kahlden in 1893 
 and 1 901, who examined five chronic cases, and gave it as his 
 opinion that the interstitial changes present did not need any theory 
 of a primary interstitial affection for their explanation. His point 
 of view was certainly influenced, if not determined, by his theory of 
 the nature of inflammation in general ; in common with YVeigert he 
 regarded all inflammation in a parenchymatous organ as primarily 
 parenchymatous in nature. Other authors adopted a middle view 
 between the two extremes. Schmaus. Schwalbe, Lovegren, and 
 Praetorius pointed out the possibility of simultaneous affection of 
 both the parenchymatous and interstitial elements, and laid stress 
 on the difficulty of solving the problem along morphological lines. 
 
 As a result of these studies the important conclusion was 
 
92 EPIDEMIC INFANTILE PARALYSIS 
 
 arrived at, that the same process occurs in adults as in children ; 
 Combault in 1873 substantiated the theory of Duchenne that a spinal 
 paralysis of adults exists, analogous to the spinal paralysis of 
 children. 
 
 (b) Investigation of Acute Gases. — The problem had not 
 reached solution by means of examination of chronic cases; more 
 was to be hoped of examination of acute cases. 
 
 We owe the first comprehensive and thorough investigations to 
 Rissler. In three acute cases he found interstitial change as well 
 as degeneration of the ganglion cells; although the stroma was 
 markedly affected he contended that the cells were primarily 
 affected because: " The pathological changes in the neighbourhood 
 of the cells were neither so constant nor sufficient to be considered 
 to be the cause or even a contributory cause of the cell degenera- 
 tion." He bases his argument largely upon one case, in which 
 cell degeneration was very marked, while interstitial changes were 
 but slight. Rissler admitted the possibility that the morbid agent 
 might have an effect upon the walls of the blood-vessels as well. 
 He was the first to prove that the pia was involved by the disease. 
 Leegaard (1889), Gowers (1892), and Monckeberg (1903) agreed with 
 Rissler's view. Monckeberg found poliomyelitis acutissima in a 
 case of Landry's paralysis. He indicated one difficulty inherent in 
 the theory that the localization of the disease depends upon the 
 distribution of the blood-vessels: "How is one to understand the 
 special liability to disease of certain regions, particularly the central 
 portions of the cord in poliomyelitis?" He considers the theory 
 of Goldscheider not a very happy one: "That the vessels in that 
 region have certain peculiarities in their walls, and that the condi- 
 tions of pressure of the stroma are different to those in other por- 
 tions." Monckeberg agrees with Weigert's view that there is 
 primary damage to the ganglion cells with secondary change in 
 the vessel walls, rendering them more permeable to leucocytes. 
 " In poliomyelitis we find the typical picture of inflammation in a 
 parenchymatous organ." In quite recent times (191 1) Cassirer has 
 given his adherence to the theory of primary involvement of the 
 ganglion cells. 
 
 At the same time it is impossible not to realize that the more 
 Investigation of acute cases has been carried out the more opinion 
 has inclined towards a primary interstitial, vascular process. Cer- 
 tain investigators, Dauber (1893-94 — a five days' case), Redlich 
 (1894 — a ten days' case), Medin (1898), Neurath (1905 — a three 
 days' case), leave the question an open one and prefer to suppose a 
 simultaneous affection of both parenchyma and interstitial tissue. 
 But most investigators adopt the " interstitial " theory. Gold- 
 scheider (1893 — a twelve days' case) was particularly impressed by 
 the intensity of the vascular change, and goes so far as to state that 
 the localization of the disease is determined by the vascular changes. 
 He draws attention to the manner in which the central artery is 
 affected (with reference to Kadyis's work), and holds that the cell 
 
PATHOLOGY AND PATHOGENESIS 93 
 
 degeneration is secondary and due to nutritional disturbance. 
 Siemerling (1894 — an eight days' case) also regards the vascular 
 changes as the essential feature. Similar views were expressed 
 subsequently by Bickel and Roder (1898), Biilow-Hansen and 
 Harbitz (1899), Matthes (1899), Placzek (1901), Marinesco (1901), 
 and Batten (1904). 
 
 Wickman's Investigations. — The work of Wickman (1905) was 
 of extreme importance not only because of its extent (seven acute 
 cases, three of Rissler's cases re-examined, and two cases during 
 Convalescence) and its thoroughness and clearness of description, 
 but also because of the expert critical analysis of all the vexed 
 points in the pathology and pathogenesis of the disease which it 
 contains. He raised the questions, really for the first time, of the 
 point of entrance, the method of infection and of spread of the virus. 
 The conclusions drawn from his exhaustive studies are extremely 
 valuable. In 1910 he amplified them by the study of seven more 
 acute cases. 
 
 In the following I shall not give Wickman's results in detail. 
 I propose to compare the results I obtained by microscopical 
 examination of cases of experimental poliomyelitis in monkeys in 
 each case with those obtained by research in man; I shall refer 
 mainly to the investigations of Wickman in this connection because 
 his descriptions are so clear and his illustrations so excellent that 
 is is easy for the layman in microscopic pathology, as I must con- 
 sider myself to be, to arrive at a clear understanding of his mean- 
 ing. The following is a short sketch of the more important 
 theoretical conclusions arrived at by Wickman. 
 
 The symptoms of poliomyelitis acuta of both adults and 
 children (the lesions are the same in both) are due to an inflamma- 
 tory process in the central nervous system. This process is not 
 limited to the spinal cord, but occurs in a disseminated form in the 
 medulla, pons, cerebellum, cerebrum, and meninges. It is essen- 
 tially therefore a disseminated meningo-myelo-encephalitis. Not 
 only the anterior horns, nor even the grey matter in general, but 
 also the white matter and the pia mater are affected; the process is 
 usually most intense in the anterior horns in the cervical and lum- 
 bar enlargements. The variation in the intensity of the process is 
 dependent upon the varying richness of blood supply to the parts. 
 Both parenchymatous and interstitial changes are found; the latter 
 are particularly well marked. Changes in the ganglion cells are 
 never found in the absence of interstitial lesions, but the opposite 
 condition is present sometimes. The process therefore is mainly 
 interstitial and of the infiltrative, lymphocytic type. The infiltra- 
 tion mainly follows the distribution of the blood-vessels. Inflam- 
 matory oedema also plays some part in the pathology. 
 
 Within the nervous system the inflammation travels along the 
 perivascular lymphatics ; the perineural lymphatics probably carry 
 the infection from the site of inoculation to the spinal cord. The 
 alimentary tract is probably the site of infection in most cases, 
 
94 EPIDEMIC INFANTILE PARALYSIS 
 
 because, clinically, intestinal symptoms are common, and the para- 
 lysis usually begins in the lower limbs. 
 
 As a side issue it is important to note that Wickman established 
 the identity of Landry's paralysis and certain forms of myelitis 
 with poliomyelitis. These investigations into the microscopic 
 pathology of the disease formed the basis of his later clinical studies 
 and enabled him to obtain a comprehensive view of these diseases, 
 which differ so much in their symptomatology and yet are probably 
 identical in their etiology. His well-deserved clinical discoveries 
 were the ripe fruit of his careful pathological studies. 
 
 More Recent investigators. — These have been numerous since 
 Wickman (Forssner and Sjovall, Harbitz and Scheel, Barnes and 
 Miller, Kadwalader, Marburg, Hoffmann, Hochhaus, Bauer, 
 Strauss, Benecke, Pirie, Marchand). The results of Harbitz and 
 Scheel are important both because their material was extensive 
 (thirteen cases) and because they differ from Wickman on one point. 
 They consider that the infection is carried to the central nervous 
 system by the blood as well as by the lymph-stream; the vessels of 
 the meninges are attacked first, and the infection then follows the 
 vessels into the substance of the cord. Forssner and Sjovall lay 
 stress on the role played by phagocytes in the destruction of the 
 ganglion cells, and Wickman, who paid little attention to this point 
 in his earlier works, recognizes its importance in his later ones. 
 These two authors have the credit of being the first to describe 
 the affection of the spinal ganglia, which discovery has been con- 
 firmed by Marburg, Strauss, Harbitz and Scheel, and Bauer. In 
 his latest work Wickman has described round cell infiltration in the 
 subpericardial fat. 
 
 These are the results so far of investigation by methods of 
 microscopic pathology. Now that it is possible to produce experi- 
 mentally a symptom complex in monkeys similar to that which 
 occurs in man, we may hope that the doubtful points will be 
 cleared up. The problems of the pathogenesis of the disease 
 are : — 
 
 (i) Where is the most common point of entry of the virus? 
 
 (2) Along what route does the virus reach the brain and spinal 
 cord? 
 
 (3) How does its further distribution within the central nervous 
 system take place ? 
 
 (4) What point in the central nervous system is first affected ? 
 
 II— THE DISTRIBUTION AND SPREAD OF THE 
 VIRUS WITHIN THE ORGANISM. 
 
 The Demonstration of the Virus in Different Organs. — It is of 
 
 primary importance, if the above questions are to be solved, to 
 know where in the body the virus may be found. As the virus is 
 so stable, we may assume that the distribution of it which is found 
 in the cadaver holds good for the living body. In the next place 
 
PATHOLOGY AND PATHOGENESIS 95 
 
 it is necessary to distinguish between the distribution found in man 
 and that found in the monkey; in the latter the disease has been 
 produced only experimentally by methods which we know do not 
 correspond to the natural method of infection for the most part, 
 or which we know to be but imperfect imitations. So far, the only 
 way to prove the existence of the virus has been by means of experi- 
 ments with monkeys, and the method of intracerebral injection has 
 shown itself to be the most certain in its effects. 
 
 (a) In Man. — As has been shown in the chapter on the etiology, 
 the virus was first proved to be present in the spinal cord of persons 
 dead of Heine-Medin disease, as was to be expected a priori. The 
 virus has also been found in the brain, specially in the cortex ; 
 whether it is always present in this situation, even when the clinical 
 symptoms are purely spinal in character, cannot be stated definitely. 
 
 All attempts to demonstrate the virus in the cerebrospinal fluid 
 have failed; this is extremely unfortunate as its presence would 
 have been an important aid to diagnosis. I have injected fluid from 
 two severe acute cases into monkeys; one of the cases was in the 
 earliest paralytic stage. Flexner and Lewis have had equally nega- 
 tive results; in 1907 they gave intracerebral and intraperitoneal 
 injections to monkeys without any result. The experience of 
 Leiner and v. Wiesner, Strauss and Huntoon, Netter, Potpeschnigg 
 and Selter has been similar. Experiments with the blood of persons 
 actually ill with poliomyelitis or dead of the disease have had the 
 same negative result. 
 
 Owing to the analogy which exists between poliomyelitis and 
 rabies I thought of the possibility that the virus might be found in 
 the salivary glands. I therefore gave intracerebral injections to 
 monkeys of emulsions of the parotid gland and pancreas of a case 
 which had died during- the acute stage of the disease; the result was 
 negative. The virus was present in the central nervous system of 
 this case in a fully virulent form (cf. p. 41). In order to test the 
 excretion of the virus I filtered the saliva of several children, after 
 having - diluted it with saline, through a Berkefeld filter; intra- 
 cerebral injection of the filtrate into monkeys produced no effect. 
 
 The virus has been found in only one situation outside the 
 central nervous system in man. Flexner and Lewis proved it to be 
 present in the mesenteric glands of a child which had died of acute 
 poliomyelitis; the injection of an emulsion of the glands into a 
 monkey produced the disease after an incubation period of ten 
 days. In no other instance has the presence of the virus anywhere 
 in the human body been proved except in the central nervous 
 system. Experiments in this direction have been so far few, and 
 more extended researches are necessary. Similar experiments with 
 monkeys are useful as supplementary studies. 
 
 (b) In Monkeys. — In these animals the central nervous system 
 is the chief place where the virus is found, more particularly in the 
 regions corresponding to the paralysed limbs. In order to make 
 as sure as possible of a successful result, those segments of the 
 
g6 epidemic infantile paralysis 
 
 cord should be used which correspond to the limb most recently 
 attacked. The virus is found wherever the typical lesions occur, 
 i.e., in the medulla, pons and brain. 
 
 The experience of most authors with cerebrospinal fluid has 
 been negative (Landsteiner and Levaditi, Leiner and v. Wiesner, 
 Romer), even with the most varied methods of inoculation. Flexner 
 and Lewis alone obtained positive results and only when they used 
 the fluid of monkeys which had received either intracerebral or 
 intraspinal injections of the virus and when the fluid was removed 
 during" the pre-paralytic stage. They found also that the fluid 
 withdrawn at this time gave evidence of a recent pial infection, 
 being cloudy and containing more cells than normal and an in- 
 creased amount of albumin. Human cerebrospinal fluid presented 
 the same appearances and Flexner and Lewis express the hope that 
 with the aid of monkeys the inoculation of cerebrospinal fluid may 
 prove of use in the establishing of an early diagnosis. At the same 
 time it must be remembered that the virus has been found only in 
 monkeys infected by the intracerebral or intraspinal method, which 
 certainly does not correspond to the method of infection occurring 
 in man. Flexner and Lewis report that when paralysis has set in 
 the cerebrospinal fluid becomes clear again, as is the case in man, 
 and that it no longer contains virus in a virulent state. 
 
 We ourselves have been unable to find any evidence that the 
 virus is present in the blood of infected monkeys; Flexner and 
 Lewis, as well as Leiner and v. Wiesner, have had the same 
 experience in the main. In one instance the Austrian observers 
 were able to find virus in the blood; this was during the paralytic 
 stage. They have never found it in the stage of incubation, which 
 is important from the point of view of the theory that the virus 
 is carried by the blood. Flexner and Lewis obtained a positive 
 result in one case by using a very large quantity of blood (25 c.c. 
 intravenously), withdrawn after paralysis had set in; the monkey 
 became ill only on the seventeenth day, so that the amount of virus 
 present in this very large amount of blood was probably small. 
 
 Experiments with spleen pulp, liver, kidney, and bone marrow 
 were negative throughout and confirmed the previous negative 
 results with blood (Flexner and Lewis, Leiner and v. Wiesner). In 
 view of these results it is improbable that the virus is carried to 
 any extent by the blood-stream. 
 
 The question of the excretion of the virus has been studied in 
 a number of experiments. Saliva, bile, urine, and intestinal con- 
 tents have been found free of virus by many authors. We our- 
 selves obtained a negative result when using the contents of the 
 small intestine of a monkey which had severe gastro-intestinal 
 symptoms and in which the mesenteric glands were much swollen 
 and contained highly virulent virus. 
 
 Monkey 50 (Rhesus). — On April 25, 1910, -received simultaneously 
 an intracerebral (1 c.c.) and an intraperitoneal (5 c.c.) injection of extract 
 of the contents of the small intestine filtered through a Berkefeld filter and 
 remained well. 
 
PATHOLOGY AND PATHOGENESIS 97 
 
 At first we considered the possibility that the virus was excreted 
 into the intestine, but in view of the experience of ourselves and 
 others that possibility must be rejected; even the injection of the 
 mucous membrane of the stomach and intestines has produced no 
 result (Flexner and Lewis, Leiner and v. Wiesner). Landsteiner 
 and Levaditi found virus once in the saliva, but they lay little 
 stress on this case in view of the consistently negative results of 
 their further experiments. Leiner and v. Wiesner found no virus 
 in the salivary glands, which coincides with our own experience. 
 
 So far the injection of the organs of monkeys had produced 
 practically no results. The following- positive experiments are of 
 more importance. Flexner and Lewis began with the idea that, 
 considered epidemiologically, there were many points of similarity 
 between epidemic poliomyelitis and epidemic meningitis (cf. Chap- 
 ter V). In previous experiments they had proved that in monkeys 
 previously infected intracerebrally with the meningococcus the 
 organism was found in the nasal mucous membrane; conversely 
 they had found that after infection of the nasal passages the virus 
 wandered to the meninges. It now occurred to them to examine 
 whether also in poliomyelitis the nasal mucous membrane acts as 
 the point of entrance and of excretion of the virus. They succeeded 
 in demonstrating that the mucous membrane of the nose and 
 pharynx of monkeys after intracerebral infection contained the 
 virus; emulsions of the mucous membrane, filtered through a 
 B'erkefeld filter, when injected into the brain of a monkey, promptly 
 produced paralysis. The blood contained in the mucous membrane 
 could not have contained the virus since the experiments detailed 
 above had proved that the blood contains either no virus or at 
 most the minutest quantity. Leiner and v. Wiesner confirmed the 
 results obtained by the American experimenters. Osgood and 
 Lucas found virus in the mucous membrane of the nose and 
 pharynx eight w r eeks and even six months after intracerebral 
 infection. Owing to the remarkable similarity betwen epidemic 
 meningitis and poliomyelitis one is inclined to believe that the virus 
 is excreted by way of the nasal mucous membrane, but the fact 
 must not be lost sight of that there is no direct proof available 
 that the secretion contains the virus; Flexner and Lewis, as well 
 as myself, have failed to find the virus in mucus from the nose of 
 human beings. 
 
 The discovery of the virus in the olfactory lobes after successful 
 inoculation of the nasal mucous membrane by Landsteiner and 
 Levaditi is of first-rate importance, as showing that the virus follows 
 the track of the nerves. 
 
 Experiments showing the relation of the glands to the virus 
 are of much importance. Flexner and Lewis obtained a positive 
 result by the subcutaneous method; they found the site of inocu- 
 lation free of virus, but the corresponding glands, as well as the 
 spinal cord, contained virus. The virus had been absorbed by way 
 of the lymphatics beyond the possibility of doubt. Still more im- 
 
 7 
 
98 EPIDEMIC INFANTILE PARALYSIS 
 
 portant, it seems to me, are the results obtained by Joseph and 
 myself. We proved that after intracerebral injection the virus 
 passed to the mesenteric glands. 
 
 Monkey 38 received an intracerebral injection on March 2, 1910. 
 On the 10th depressed; much diarrhoea. On the nth, condition the same; 
 in addition, slight paresis of all limbs; 12th, universal paralysis; died at 
 noon. The autopsy revealed typical microscopical changes. Swelling of 
 the mesentric glands was very marked; the coils of intestine appeared red, 
 and the lymph follicles and Peyer's patches were swollen. The mesenteric 
 glands were proved to contain no bacteria on microscopical examination, 
 and were preserved in glycerine. On March 22, monkey 42 received an 
 intracerebral injection of an emulsion of the glands. It remained well until 
 April 1. On the 2nd, sudden severe paralysis of the hind limbs and slight 
 paresis of the fore limbs set in ; the paralysis became worse during the day, 
 and was total in all limbs by the evening. The animal was found dead on 
 the 3rd. The autopsy showed typical, intense changes. 
 
 I shall discuss the clinical and pathological importance of this 
 case later. Flexner and Lewis obtained an opposite result even 
 when the virus was injected directly into the alimentary tract. On 
 the other hand, the more systematic research of Leiner and v. 
 Wiesner confirmed and amplified our results. In the case of 
 monkeys killed during the first days of illness after intracerebral 
 injections they found virus in the submaxillary glands, glands of 
 the neck, the mesenteric and prevertebral glands ; the inguinal 
 glands were found to be free of virus. In so far as these experi- 
 ments allow of a general interpretation we may say, that after 
 intracerebral injection in monkeys the virus passes with ease from 
 the spinal cord to the glands in its vicinity. Leiner and v. Wiesner 
 arrived at the conclusion that the type of disease produced by 
 inoculation with virus from the glands was a not very severe one. 
 
 Conclusions. — The general impression produced by the fore- 
 going recital of results obtained is perhaps rather confusing; yet, 
 on the whole, the results make up a very uniform picture of the 
 distribution of the virus within the bodies of human beings and 
 monkeys. The virus has a strong affinity to the central nervous 
 system and is found in the greatest quantity there. The other 
 organs are practically free of the virus. The relation of the virus 
 to the lymphatic system is exceedingly remarkable ; it seems to 
 indicate that the virus tends to spread to organs which contain 
 much lymphoid tissue. The objection, that the experiment merely 
 indicates the absorption of the virus from the alimentary tract, may 
 be brought against the results of examination of the mesenteric 
 glands in man; the same examination in monkeys, which had 
 received an intracerebral injection, is not open to that objection, 
 and the result shows that the virus travels by way of the lymphatics 
 and possibly develops in them. At first I was inclined to look upon 
 the presence of the virus in the mesenteric glands of monkeys which 
 had received an intracerebral injection as evidence that the virus 
 was carried by the blood. On considering the results as a whole and 
 
PATHOLOGY AND PATHOGENESIS 99 
 
 particularly the fact that the blood is usually free from virus, it 
 seems to me more probable that the virus passes by the lymphatics. 
 That virus has been found in the mucous membrane of the nose 
 and throat, is a further instance of the affinity of the virus for 
 lymphatic tissue; Flexner and Lewis hold the view that the virus 
 is most probably carried from the meninges to the mucous mem- 
 brane by the lymph channels. Key and Retzius proved the exist- 
 ence of such channels when they found that injection of the sub- 
 arachnoid space caused injection of the lymphatics of the nasal 
 mucous membrane. The marked richness in lymphatic tissue of the 
 nose and throat is another argument in favour of the existence of 
 such an affinity. 
 
 The Methods of Inoculation. — From all that we know of the 
 relation the virus bears to the central nervous system, it is clear 
 that the intracerebral method is the most certain. Intraspinal 
 inoculation is usually successful. Leiner and v. Wiesner observed 
 a certain regularity in the occurrence of paralysis after intracerebral 
 injection; they found that the limb opposite to the side where the 
 injection was made was affected first and that it was usually the 
 hind limb. They made the injection usually into the central con- 
 volutions as near the vertex as possible. After hearing of this 
 observation made by the Austrian writers, we re-examined our 
 material from this point of view, and with the following interesting 
 result. I must mention first that, owing to the position of the 
 operating table, we happened to make all our injections on the 
 left side of the skull in the region of the central gyri; in the case 
 of all the injections we entered only so far from the mid-line as 
 to avoid wounding the longitudinal sinus. This situation cor- 
 responds with the fact that the lower limbs were affected first in 
 most of our cases. Paralysis appeared first in the left hind limb 
 of only one monkey out of twenty which had been injected on the 
 left side. In eight cases one side was not affected before the 
 other, but it must be remembered that at the time we were not 
 paying special attention to this point. In no less than eleven 
 experiments the limbs on the right side were paralysed first. In 
 the majority of the cases the paralysis began in the right hind limb 
 and then affected the left hind limb. When the fore limbs were 
 involved first, it was the right one, with one exception, which was 
 affected. Unfortunately, at the time w T hen we became aware of 
 the importance of this question we had almost finished our series 
 of experiments. I may mention, however, that both monkeys 
 injected ad hoc on the right side became paralysed first in the 
 contralateral limbs. Should these observations be confirmed they 
 would seem to indicate that the active agent spreads along the 
 neuron or, at least, spreads more quickly in this direction than in 
 any other. It is to be supposed that in doing this it passes along 
 the lymph channels accompanying the neuron, although this would 
 pre-suppose a considerable degree of isolation of these channels. 
 A large number of experiments, directed towards this particular 
 
IOO EPIDEMIC INFANTILE PARALYSIS 
 
 question, are necessary; they should include as many variations 
 in the method of injection as possible. 
 
 Direct injection into the nerves is a method which is of 
 particular interest. The authors who have tried this method are 
 unanimous that it is very effective and that paralysis always occurs 
 first in the limb corresponding- to the nerve injected (Flexner and 
 Lewis, Landsteiner and Levaditi, Leiner and v. Wiesner). This is 
 confirmatory of the views expressed by Wickman, Harbitz, and 
 Scheel, that the virus follows the course of the nerves. Leiner 
 and v. Wiesner designed a very beautiful experiment to illustrate 
 the point. They first ligatured the sciatic nerve of a monkey, then 
 injected the nerve peripheral to the ligature and finally severed the 
 nerve at the ligature. The monkey remained well, while another 
 monkey, in which the sciatic nerve was injected without previous 
 ligature, quickly became paralysed in the corresponding limb. This 
 progress of the virus along the nerve may be compared with the 
 absorption of the virus of rabies and of tetanus. If we accept the 
 view of Meyer and Ransom, that the axis-cylinder itself carries 
 the virus in the latter case, it is more probable that the living virus 
 of poliomyelitis wanders in a centripetal direction along the peri- 
 neural lymphatics. The experiment confirms Wickman's theory 
 that the virus reaches the central nervous system primarily by way 
 of the nerves. 
 
 Other authors incline to the view that the infection is hemato- 
 genous. It is true that intravenous injection can cause the 
 disease, but the method is an uncertain one. Landsteiner and 
 Levaditi have shown that successful infection is produced even 
 when the virus has to pass through the liver (injection of a mesen- 
 teric vein). This demonstration that infection is possible via the 
 blood-stream is no proof that the virus reaches the central nervous 
 system by that channel. We shall return to this later. 
 
 So far it has proved impossible to inoculate through the 
 unbroken skin; on the other hand, infection by subcutaneous in- 
 jection has been successful in a few instances. The virus passes, 
 in part at least, through the lymphatic glands (cf. the experiment 
 of Flexner and Lewis quoted above). Direct injection into the 
 lymphatic glands has been successful. As in rabies, inoculation 
 into the anterior chamber of the eye has produced the disease 
 (Leiner and y. Wiesner, Landsteiner and Levaditi). It is doubtful 
 whether intraperitoneal injection alone will give a positive result. 
 
 It follows from all these successful artificial methods of 
 inoculation that, in the case of the monkey, which is as susceptible 
 as man to the disease, a positive result can be obtained with 
 certainty only when the virus is brought into direct contact with 
 nervous tissue. These experiments, however, only go to prove 
 what route the virus takes when it is once within the body. They 
 show that the active agent is certainly capable of reaching the 
 central nervous system by way of the perineural lymph spaces. 
 This is not disproved by the fact that direct intravenous injection 
 
PATHOLOGY AND PATHOGENESIS IOI 
 
 has been successful; we know that, in the case of tetanus, intoxica- 
 tion by way of the blood-stream is promptly successful, but that 
 the toxin does not pass straight from the blood to the brain and 
 spinal cord, but is absorbed by the peripheral endings of the nerves. 
 It is interesting- to note that in successful intravenous injections the 
 paralysis occurred first in the upper half of the body, i.e., in the 
 segments of the cord which are furnished with relatively short 
 peripheral nerves. 
 
 Attempts to determine the Point of Entrance of the Virus.— 
 The following experiments help to elucidate this problem. They 
 are based upon clinical experience, which indicates the upper and 
 lower respiratory tract (sore throat, coryza, and bronchitis) or the 
 alimentary tract (gastro-intestinal symptoms) as the portal by which 
 the virus enters. It is not easy to cause infection through the 
 nasal mucous membrane ; Landsteiner and Levaditi obtained no 
 results through the undamaged mucous membrane ; they were 
 successful when the virus was injected into the mucous membrane, 
 the infection following the nerves (the virus was found in the 
 olfactory lobe) and causing the "type superieur " of poliomyelitis. 
 Flexner and Lewis succeeded by rubbing in the virus. Leiner and 
 v. Weisner first cocainized the mucous membrane and then rubbed 
 in the virus with a hard brush. Infection through the nasal mucous 
 membrane is thus undoubtedly possible; it appears to be necessary, 
 however, for the mucous membrane to be injured in some way 
 previously. 
 
 Flexner and Lewis had no success with tracheal injections and 
 inhalation; on the other hand, the same methods proved immediately 
 successful in the hands of Leiner and v. Wiesner. Paralysis 
 occurred in these cases first in the upper half of the body, in the 
 neck and arms. In some instances the paralysis remained limited 
 to these regions, in others it descended. The same authors have 
 done much to clear up the problem of infection through the 
 alimentary tract. Their experiments had no result at first. They 
 then fed monkeys, which had been starved for twelve to twenty- 
 four hours, and in which peristalsis had been diminished by means 
 of opium, with the virus; this was effective. Paralysis was pro- 
 duced also by direct injection of virus into a loop of small intestine. 
 In these experiments the paralysis always affected the lower half 
 of the body first. Krause and Meinicke were not successful by the 
 method of feeding monkeys with virus, nor were Landsteiner and 
 Levaditi, although they used large quantities. 
 
 One is impressed, even more than in the experiments on the 
 nasal mucous membrane, with the fact that infection is only possible 
 under certain conditions. 
 
 These experiments, however, give some support to the clinical 
 views mentioned above. 
 
 Finally, an observation may be recorded here which has been 
 made by all the workers in this field. In no case has spontaneous 
 infection of a monkey ever been observed. In the course of our 
 
102 EPIDEMIC INFANTILE PARALYSIS 
 
 own experiments healthy monkeys were kept in quite small cages, 
 together with monkeys which had been infected and with those 
 which were actually suffering from the disease. Leiner and v. 
 Wiesner purposely brought healthy monkeys into close contact 
 with diseased monkeys, and no infection resulted. One may 
 suppose that monkeys are not liable to infection in the natural way, 
 although this is contradictory to the experience that they can be 
 infected by way of the natural portals of entry of the virus and 
 that they are very dirty among themselves. It is more probable 
 that the artificially infected animals do not excrete the virus. It 
 is in favour of this theory that the virus was never transmitted 
 to anyone who was occupied with the animals, nor was it carried 
 by them to their relatives or to any other persons, although the 
 animals had to be kept in our laboratory itself from lack of other 
 rooms which could be kept warm. 
 
 III.— THE PATHOLOGICAL CHANGES FOUND 
 IN EXPERIMENTAL POLIOMYELITIS IN 
 MONKEYS COMPARED WITH THOSE 
 FOUND IN MAN. 
 
 It is not claimed that the statements made in this section are 
 the result of a systematic study of the pathological picture presented 
 by experimental poliomyelitis in monkeys, and they should not be 
 regarded as such. Our time was too much taken up with the 
 purely experimental side of the work (apart from other studies 
 altogether) for us to be able to make that detailed study of the 
 histology of the disease which is both necessary and desirable. 
 We were obliged to use a great deal of our material for research 
 into the nature of the virus, the means of preserving it and the 
 question of immunity. Usually we were satisfied with the examina- 
 tion of small pieces from the lumbar cord, particularly the lumbar 
 enlargement, the cervical enlargement, the medulla, the central 
 ganglia and the cerebral cortex. We consider such an examination 
 to be of the utmost importance, even though the clinical symptoms 
 appear quite conclusive; otherwise serious errors may occur, as in 
 our experience with cerebral abscesses. Histological examination 
 is very reliable ; in cases where we saw no lesions we were unable 
 to prove the presence of virus. On the other hand, the finding 
 of typical acute microscopical changes was followed usually by a 
 positive result in the inoculation experiment. I will say at once 
 that we made no microscopical examination of organs, apart from 
 the central nervous system. As far as I know there is only one 
 observation on record : Plexner found a round-celled infiltration 
 close to a vessel at the site of a subcutaneous inoculation. There 
 is a wide field for research in this direction. The lymphatic glands 
 might repay study; they are known to contain the virus, and I 
 think therefore that a specific lesion may be found" in them. 
 
PATHOLOGY AND PATHOGENESIS 103 
 
 Technique Directly after the death, or after the killing of the 
 
 dying monkey, the portions of the nervous system mentioned above were 
 cut out and put into 7 to S per cent, formalin for twenty-four hours or longer. 
 They were then hardened in alcohol of increasing strength for at least 
 three days. iVfter being completely dehydrated in absolute alcohol they 
 were transferred to xylol, where they remained until they were quite clear,, 
 usually two to three hours ; the xylol was changed twice. Then they were 
 put into a concentrated solution of pure xylol and soft paraffin for two to. 
 three hours, then into paraffin with a melting point of 42 for one hour,, 
 for five hours into paraffin with a melting point of 4S , and, finally, they 
 were embedded. 
 
 The sections, about 15 n thick, were cut with a microtome, and stained 
 either with hsematoxylin and eosin or with van Gieson. For demonstrating 
 any bodies which might be included in the cells we used Joest's modification 
 of Mann's stain, which he used for Negri bodies; as I have mentioned 
 above, we found no such bodies. 
 
 Thus I am unable to give results of a systematic nature. This, 
 necessary limitation perhaps does not involve any great loss; after 
 examining the brain and spinal cord for diagnostic purposes in 
 about forty monkeys, I am sure that a full description of them 
 would be monotonous. I shall confine myself to a summary 
 description, with the aid of micro-photographs, of the changes 
 found, and I shall compare these with the appearances in human 
 poliomyelitis described by Wickman. 
 
 Macroscopic Changes. — In monkeys which have died of acute 
 poliomyelitis no changes are found outside the central nervous 
 system in most cases. Occasionally small areas of broncho- 
 pneumonia were present, usually only in those monkeys in which 
 the death agony was prolonged. These changes can hardly be due 
 to the action of the virus. Redness of the intestinal mucous mem- 
 brane was common, but is probably of but little significance owing* 
 to the frequency of intestinal disturbance in monkeys kept in 
 captivity. On the other hand, we are inclined to attach importance 
 to the swelling" of the lymph follicles and of Peyer's patches, and 
 particularly to the enlargement of the mesenteric glands, since they 
 have been shown to contain virus. Landsteiner has observed in- 
 flammatory swelling's in the neck, which were more marked than 
 those due to the pharyngitis which is so common in these animals. 
 Other pathological appearances have not been seen in monkeys. 
 
 In human beings the spleen is swollen sometimes; cloudy 
 swelling and even inflammation of the kidneys has been observed, 
 and in some cases the tonsils were sw'ollen (Beneke). Swelling" 
 of the follicles and Peyer's patches were relatively common. 
 
 The macroscopic changes in the brain and spinal cord of mon- 
 keys dead from acute poliomyelitis may be so little characteristic, 
 that even when one has had much experience it is not possible to 
 say definitely whether a lesion is present or not, and certainly not 
 to say that true poliomyelitis is present, even when the microscope 
 reveals typical and well-marked changes. In the majority of cases, 
 however, macroscopic changes are more obvious. On removal of 
 
io4 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 the skull-cap the pressure within the dura is found to be raised; 
 there is an excessive flow of clear cerebrospinal fluid when the 
 dura is turned down. The pia mater on the surface of the brain 
 is congested, the surface itself is shiny and moist. Compared with 
 the normal monkey's brain, which is of a yellowish white colour, 
 the brain appears diffusely red; on section this redness is seen to 
 be most marked in the grey matter, which has an almost violet 
 tinge. The convolutions are often flattened. On section the brain 
 
 " S ' " , -*■* v-.-'c '. 
 
 h,:- \*s$ -TV^y '■ . '•-' * '. '--A . - i-- 
 
 v.- -•*--^.-K 
 
 Fig. 17. 
 
 The greater part of the right half of the spinal cord of a normal monkey. 
 Above and to the left, the anterior longitudinal fissure ; above the centre, 
 the right anterior horn. To the left, and below, the posterior horn. 
 
 is markedly cedematous. The changes in the spinal cord are more 
 ■constant. The dura is more distended than usual, and an excessive 
 amount of fluid escapes when it is opened. In quite acute cases 
 only is there a slight opacity, with a corresponding increase in the 
 •number of cells present (lymphocytes). Generally it is quite clear. 
 
PATHOLOGY AND PATHOGENESIS 
 
 I05 
 
 The pia mater is congested. The cord is moist, smooth, and in 
 places softer than normal, although without any true softening 
 being present. The grey matter is distinctly more red than normal; 
 this is most marked in the segments corresponding to the distribu- 
 tion of the paralysis. The anterior horns are most affected, but 
 frequently the whole grey matter stands out in a red-violet colour. 
 On looking closely minute drops of blood are seen in the grey 
 matter; microscopical examination shows that these are almost 
 
 
 ■S-^^l 
 
 n& 
 
 ■ "■'• •>■/ - 
 
 Fig. 18. 
 
 Section of the lumbar cord of monkey Xo. 58. To the right and above, 
 the slightly affected right anterior horn with infiltration into its substance and 
 into the veins. In the middle, the central canal; just to the left an in- 
 filtrated artery; still more to the left, the left anterior horn, slightly 
 infiltrated. 
 
 always haemorrhages into the substance of the cord. The white 
 matter appears quite normal or perhaps slightly cedematous. 
 
 The macroscopical appearances in man are so exactly similar 
 to those just described that it is unnecessary to deal with them. 
 
io6 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 Definite morbid changes appear to be rather less frequent; that 
 they are relatively more marked in the monkey may be due to the 
 intracerebral method of infection. 
 
 Microscopic Changes. — In monkeys these are usually much 
 more widespread than would be expected from the macroscopic 
 changes or the clinical symptoms. The microscopic lesions are- 
 more intense and constant in the spinal cord than in the brain. I 
 mention this point specially because we are dealing with monkeys 
 infected by way of the brain. In most cases a glance at the section 
 under a low magnification is enough to settle the diagnosis. The 
 most obvious change seen is the remarkable increase in the number 
 
 Fig. 19. 
 
 Shows marked changes in the left anterior horn and part of the posterior 
 horn of the lumbar cord of monkey No. 24. 
 
 of cell nuclei; this is most marked in the anterior horns. In fig. 17* 
 I reproduce the appearances of the normal spinal cord; figs. 18, 19, 
 and 20 represent sections showing' the changes due to poliomyelitis 
 under the same magnification. The difference is clear even in the 
 
 * The photographs, figs. 17 to 49, were taken by myself by means of a 
 Zeiss microphotographic apparatus kindly lent to me by the firm of Behring 
 in Marburg. The objectives AA, D and E were used, and in order to obtain 
 different enlargements the length of the tube was varied, and not the eye- 
 piece. Unfortuntely, I omitted to note how far the tube was drawn out in 
 each case, so that I am unable to give the exact amount of enlargement. 
 
 Most of the photographs were taken with objective AA and a tube of 
 '65 m. 
 
PATHOLOGY AND PATHOGENESIS 
 
 107" 
 
 case of monkey No. 58 (for the clinical history see p. 77), in which 
 the changes are only slight; it is very obvious in figs. 19 and 20, 
 taken from the severely affected spinal cords of monkeys Nos. 24- 
 and 4 (cf. p. 66 and p. 42), which print more darkly, owing to the 
 increased number of cell nuclei. These illustrations, taken with a 
 low power, show that the posterior horns are also affected. A 
 
 Fig. 20. 
 
 Anterior and posterior horns from the lumbar region of monkey No. 4 ; 
 well-marked changes. The dark areas in the left anterior horn are mainly 
 haemorrhages. To the right above, a pial septum infiltrated. At the right 
 border, the fold of the pia lying in the anterior longitudinal fissure, much 
 infiltrated. Below, veins with marked infiltration, some of them passing 
 to the posterior horn. 
 
 higher magnification is necessary in order to analyse the nature of 
 the lesions. 
 
 Pia. — In the lower part of the cord the pia is much affected. 
 I found that involvement of the pia was most marked in the lower 
 lumbar region, and became less in an upward and downward 
 
ioS 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 
 
 - ';'->'-?-? : '■■- ^'^^'^S^'--'- 
 
 
 
 '&££$ 
 
 
 
 -\r- -■ -■ ''~^yMz'J'i>~-Sj 
 
 <■■ ■'"' '7/ ' '/•■'<%'*i : '~£'-':'', 
 
 
 
 
 ii 
 
 'WW 
 
 "i>^'--> ."Sis' 
 
 Fig. 
 
 21. 
 
 
 Slight infiltration of the pia at the entrance to the anterior longitudinal 
 fissure in monkey Xo. 2. Also some infiltration within the fissure. 
 
 
 Fig. 22. 
 
 Well-marked round cell infiltration in the deeper part of the anterior fissure 
 (from the lumbar cord of monkey Xo. 2). 
 
PATHOLOGY AND PATHOGENESIS 109 
 
 direction from that region. Irregularly scattered changes in the pia 
 are found in the upper segments of the cord in varying degrees. 
 
 The chief change in the pia is a round cell infiltration, which is 
 partly diffuse and partly in connection with the vessel walls. 
 
 This infiltration is more marked on the anterior surface of 
 the cord, but is found also on the posterior surface. A few round 
 cells are found in the posterior septum, but both at the entrance 
 to the anterior fissure and in the deeper parts of the process of pia 
 mater the infiltration is frequently considerable in amount. 
 
 Fig. 22 gives some idea of the amount of infiltration. Some- 
 times infiltration occurs on the antero-lateral aspect of the cord; 
 I found such a condition in a monkey which had been ill for only- 
 twelve to twenty-four hours (fig. 23). 
 
 Fig. 23. 
 
 Marked round cell infiltration of the pia on the right anterior aspect of the- 
 lower lumbar cord of monkey Xo. 1. 
 
 Infiltration of the pia is often seen between the nerve bundles 
 of the anterior or posterior roots. The blood-vessels in the pia 
 are usually distended and full of well-preserved corpuscles. Peri- 
 vascular infiltration is most marked in the depths of the anterior 
 fissure; the infiltrated vessels can be seen curving outwards to reach 
 the anterior horns. More rarely a pial septum passing through the 
 white matter is seen; I have never observed any direct extension 
 of the infiltration from the pia to the white matter. 
 
 The pia mater of the brain shows similar changes, not only at 
 the site of inoculation, where they are invariable, but also on the 
 base of the brain (vide fig. 24). 
 
 I found the dura mater normal in every case. 
 
i IO 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 FIG. 24. 
 
 Infiltrated pia from the base of the brain of monkey Xo. 4 at the entrance 
 -to a sulcus. Above and to the right there is a septum slightly infiltrated, 
 passing into the cortex. The infiltration is shown surrounding a distended 
 -vessel. 
 
 '<-'/• 
 
 /;■-'■■ % .\ iusM4 
 
 .- ■- \ •> ■ v> : ■■j>-rM ■'■■■ 
 
 m« ■ ' * ' < ■ 
 
 %\ E ' J V- - ■ '■'■ '"''"'•'r.;\ '* 
 
 Fig. 2^ 
 
 General view of a longitudinal section of a human spinal cord from a 
 .case of poliomyelitis. In the middle, the pia with much infiltration around 
 -the vessels; to the right and left of the pia, normal white matter; still further 
 
 outwards on both sides, the markedly infiltrated anterior horns. On the left 
 
 side more white matter is seen. 
 
PATHOLOGY AND PATHOGENESIS 
 
 III 
 
 The condition of the pia is sufficient to explain the irritative 
 symptoms observed in some monkeys (hyperesthesia and vomiting"). 
 
 The pathological changes found in the pia in human beings 
 correspond very closely with those just described. The pia mater 
 of the brain appears to be affected more frequently and more 
 markedly in monkeys than in man; the reasons for this are probably 
 those given above. 
 
 Spinal Cord. — In the spinal cord itself the grey matter is 
 undoubtedly the part mainly affected. This is very clearly demon- 
 strated by means of longitudinal sections. Professor Beneke has 
 very kindly allowed me to make use of one of his own longitudinal 
 sections of the spinal cord from a case of poliomyelitis from which 
 I have made photographs. 
 
 
 ■ ' ■:■:■■■. r '..■■*■■ ,;; m 
 
 "". • ■ ■?"■••■ ■ ■• ; ••-' ' : ■•$« 
 
 ■ : '" '■$■■■"■>; 
 
 i ■ ... •"■■■ .hV'}! : v^^^:V7 
 
 , ■•>. .. •- v •;. *:"■<■• *-\* : M^ 
 
 Fig. 26. 
 
 Portion of a longitudinal section of the same spinal cord as in fig. 25. 
 From left to right, a portion of the left anterior tract, the fold of pia mater 
 with marked infiltration, the right anterior tract, the right anterior horn 
 invaded by round cells. 
 
 The general view (fig. 25) shows the two infiltrated anterior 
 horns lying between bundles of normal white matter. The median 
 fissure contains infiltrated pia mater. The condition is seen more 
 clearly under a higher power (fig. 26). 
 
 The increase in the number of nuclei affects the anterior horns 
 most; it is not seen all over the anterior horns, but stands in a 
 definite relationship to the vessels. Very frequently infiltrated 
 vessels are seen passing from the edge of the fold of pia lying in 
 the anterior fissure to the anterior horns and, sometimes, to the 
 posterior horns (vide fig. 27). The peripheral vessels are affected 
 as often as the central vessels (vide fig. 28). The infiltration usually 
 
112 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 affects the adventitia, more rarely the perivascular lymph spaces. I 
 agree with Wickman that the veins are more frequently involved. 
 
 The manner in which the infiltration affects the vessels more 
 than the general substance of the cord is well shown in fig. 29. 
 
 In fig. 30 a slightly infiltrated artery and several veins with 
 marked infiltration are seen. In some instances the diffuse infiltra- 
 tion does not seem to have any relation to the distribution of the 
 vessels (figs. 31, 32), although it is very difficult to be sure on this 
 point. 
 
 Sometimes, more usually in the anterolateral portion of the 
 anterior horns, small infiltrations are seen which are quite uncon- 
 nected with any vessel; from their situation I judge that they are 
 determined by the presence of the ganglion cells. 
 
 Fig. 27. 
 Lumbar cord of monkey No. 4. 
 (cf. fig;. 20). Above, the deepest 
 part of the anterior fissure with 
 its pia. In the middle and below, 
 blood-vessels passing to the pos- 
 terior horn, much infiltrated. 
 
 
 
 FIG. 28. 
 
 Lumbar cord of monkey No. 4. 
 Antero-lateral portion of left 
 anterior horn. To the left, some 
 peripheral vessels, much infil- 
 trated, passing from the white into 
 the grey matter. The collections 
 of cells seen to the right are not 
 made up of round cells, but are 
 haemorrhages. Markedly degene- 
 rate ganglion cells are seen lying 
 in the loose, cedematous tissues of 
 the cord. 
 
 The involvement of the vessels is shown further by their 
 engorgement, which is more noticeable in the case of the veins. 
 When stained with van Gieson the vessels are seen filled with well- 
 preserved blood corpuscles. Haemorrhages into the cord are not 
 rare in acute cases; they are associated usually with interstitial 
 inflammation (cf. fig. 20). Finally, the oedema remains to be con- 
 sidered, which sometimes causes considerable loosening of the 
 
PATHOLOGY AND PATHOGENESIS 
 
 I I 
 
 Fig. 29. 
 
 Another view of the same section as in figs. 25 and 26. In the right 
 half of the illustration, two peripheral vessels with marked infiltration, lying 
 at the boundarv between white and grey matter. Otherwise similar to 
 fig. 26. 
 
 Fig. 30. 
 
 Lumbar cord of monkey No. 58 [cf. fig. 18). To the left, the central 
 canal ; close to it, an artery with slight infiltration. An infiltrated vein is 
 seen running to the anterior horn (upwards and to the right in the photo- 
 graph). Some diffuse infiltration in the anterior horn (to the right, above). 
 
ii4 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 tissues. This I found most frequently in the region of Clarke's 
 column in the upper lumbar region (cf. fig. 33); the tissues were 
 distended and formed a wide mesh-work. It cannot be merely a 
 
 Fig. 31. 
 
 Left anteiior horn in the lumbar cord of monkey No. 46. The apex 
 of the horn lies above. To the ri^ht, a vessel slightly infiltrated. In the 
 middle and above to the right, diffuse infiltration of the grey matter. 
 
 FIG. 32. 
 
 Right anterior horn (apex above) in the lumbar cord of monkey No. 24. 
 Marked, diffuse infiltration. The tissues are swollen with oedema. Vessels 
 slightly infiltrated. Ganglion cells have almost disappeared. 
 
 matter of chance that Wickman found a similar condition most 
 marked in that region in man also. 
 
PATHOLOGY AND PATHOGENESIS 1 15 
 
 Three kinds of alteration of the ganglion cells were to be seen 
 in my preparations. In many instances they had simply disappeared, 
 and it was impossible to say how this had happened. It was as 
 though they had dissolved like a lump of sugar in water. It seems 
 to me not improbable that the oedema is the active agent in this 
 process. In other cases a microscopical change preliminary to 
 disintegration could be seen. The cells lose their polygonal shape, 
 the protoplasm has a washed-out, homogeneous appearance, the 
 nucleus stains poorly. After making due allowance for the possi- 
 bility of error which Wickman has pointed out. that only portions, 
 of normal cells are seen in the sections, I was able by means of 
 serial sections to convince myself that this variety of alteration 
 exists. Strauss has shown that the first change which takes place 
 
 Fig. 33- 
 
 Upper lumbar region in monkey No. 48. Near Clarke's column. The 
 tissues are disintegrated. A small haemorrhage is present to the left and 
 somewhat upwards. 
 
 in such cases is a swelling of the intracellular network of neuro- 
 fibrils. Such a change may be the forerunner of the alterations- 
 described above, and lead ultimately to the complete disappearance 
 of the cell. The third method, which is the most unequivocal, is 
 that usually called neuronophagy. It seems to occur more fre- 
 quently in monkeys than in human beings. In his earlier researches- 
 Wickman met with it so rarely that he did not consider it of much 
 pathological importance. In monkeys it occurs frequently, and 
 several stages can be made out. Figs. 34, 35 and 36 show a certain 
 degree of neuronophagy under a low, moderate, and high magnifi- 
 cation; in figs. 37, 38, 39 and 40 an advanced stage of neuronophagy 
 is seen. 
 
lib 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 The illustrations show that neuronophagy consists in invasion 
 of the ganglion cells by round cells; the latter devour the former 
 until nothing is left of the substance of the ganglion cells, and only 
 swollen round cells remain. Wickman's suggestion is correct, that 
 neuronophagy occurs frequently in acute cases of poliomyelitis in 
 monkeys. I believe that it is just because poliomyelitis is so acute 
 in monkeys, as compared with the disease in man, that neurono- 
 phagy is so often seen in the former. The following clinical histories 
 show that the examples of neuronophagy recorded above were 
 obtained from monkeys in which the disease ran a particularly acute 
 course. 
 
 Monkey Xo. 35 suffered for a considerable time from the disease, but 
 the paralysis which caused death came on very suddenly in the form of a 
 relapse. 
 
 Fig. 34- 
 Left anterior horn from the lum- 
 bar region of monkey Xo. 35. 
 Active neuronophagy beginning in 
 the ganglion cells. Moderate in- 
 filtration of the anterior horn. 
 
 FIG. 35- 
 Enlargement of part of fig. 34. 
 The neuronophagy is more easily 
 seen. 
 
 Monkey Xo. 24 received an intracerebral injection of the virus on 
 January 25, 1910. On the 29th it became suddenly completely paralysed, 
 and it was found dead on the following morning. 
 
 Marked destruction of the ganglion cells was usually accom- 
 panied by well-marked interstitial changes. Where this appeared 
 not to be the case I found either that the tissues were much sw r ollen 
 with oedema, or that the vessels in the neighbourhood w r ere 
 markedly infiltrated. Even when there was no connection between 
 infiltration and destruction of the ganglion cells, in almost every 
 case infiltration was present in some part of the section. In order 
 
PATHOLOGY AND PATHOGENESIS 
 
 117 
 
 to come to a conclusion on this point, it would be advisable to kill 
 and examine monkeys in an earlier stage of the disease — directly 
 after the appearance of the paralysis. With our small material we 
 were unable to carry out this plan. In selecting areas for purposes 
 of photography. I tried to find one which showed this destruction 
 of ganglion cells in the absence of infiltration of the interstitial 
 substance; the failure which attended my search has led me to 
 believe that such destruction does not occur. The contrary con- 
 
 
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 Fig. 36. 
 
 High magnification of the part outlined in fig. 35. Four ganglion cells 
 undergoing neuronophagy. 
 
 dition is frequently found; cells which are quite normal, as far as 
 can be proved microscopically, are seen near or even in the middle 
 of areas of infiltration. 
 
 The posterior horns are usually less affected; they sometimes 
 show one infiltrated vessel (fig. 41). 
 
 In confirmation of Wickman's observation in human beings, 
 that in the upper lumbar and lower dorsal regions the posterior 
 
ii8 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 horns seem to bear the brunt of the attack, I may refer to the section 
 made from the upper lumbar region of monkey No. 48; fig. 42 
 
 Fig. 37. 
 
 lumbar cord of monkey No. 24. Left anterior horn. An infiltrated 
 septum is passing- from the white matter above and to the left to the anterior 
 horja. Marked neuronophagy in the horn. 
 
 Fig. 38. 
 Increased magnification of the part outlined in fig. 37. 
 
 represents the anterior horn, but little damaged; fig. 33 the marked 
 swelling up of the tissues in the region of Clarke's column; and 
 
PATHOLOGY AND PATHOGENESIS 
 
 119 
 
 Fig. 39- 
 Still higher magnification of the part outlined in fig. 38. 
 
 
 Fig. 40. 
 Very high magnification of the part outlined in fig. 39. 
 
I.20 EPIDEMIC INFANTILE PARALYSIS 
 
 fig. 43 the changes in the posterior horn in the same section. 
 Speaking- generally, however, the changes are much less marked in 
 the posterior horns, and the nervous tissue suffers much less 
 destruction in them. 
 
 In the neighbourhood of the central canal, tissue infiltration is 
 generally only slight, but the vessels are much involved, the arteries 
 relatively less than the veins (fig. 30). I always found the ependyma 
 unaffected. Wickman occasionally observed infiltration of it in 
 human beings. 
 
 When the white matter is affected at all, it shows only slight 
 infiltration of the tissues or of the vessels. An infiltrated pial 
 septum may traverse the white matter, but the infiltration never 
 invades the white matter itself. I could not find any relation 
 
 Fig. 41. 
 Infiltrated vessel in the right" posterior horn: from the middle of the lumbar 
 
 cord of monkey No. 4. 
 
 between the areas affected in the white matter and those in the 
 grey. 
 
 I did not examine the spinal ganglia. According to Flexner 
 and Lewis, Landsteiner and Levaditi, changes are seen in them 
 similar to those observed in man, diffuse infiltration lying between 
 the ganglion cells and between the nerve fibres while the ganglion 
 cells are degenerate. 
 
 The peripheral nerves were not examined. Slight degenera- 
 tive changes have been observed in human beings, but no inflam- 
 matory lesions (Redlich, Monckeberg). 
 
 Changes similar to those in the spinal cord are found in the 
 medulla and pons. The areas affected are generally smaller, further 
 apart from one another, and distributed in an irregular manner. 
 
PATHOLOGY AND PATHOGENESIS 
 
 121 
 
 The vessels are most affected, and this is very obvious because of 
 the distance between the areas involved. Wickman's observation 
 that these areas bore no relation to the nuclei of the cranial nerves 
 
 x£ 
 
 \ 
 
 Fig. 42. 
 
 Anterior horn, slightly infiltrated, from the upper part of the lumbar cord 
 
 of monkey Xo. 4S. 
 
 *:>■ 
 
 Fig. 43. 
 
 Round cell infiltration in the posterior horn from the upper lumbar region 
 
 of monkey Xo. 48. 
 
 is generally true also in monkeys. Occasionally very distinct, small 
 infiltrations are seen which are clearly in relation to ganglion cells; 
 they are found to be examples of neuronophagy. On the other 
 
122 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 hand, infiltration of the vessels in the pons and medulla is common, 
 even when the clinical history does not lead one to expect it. 
 
 Brain. — Infiltration is seen most frequently (when it is seen at 
 all) in the cortex near the site of inoculation. It is often not more 
 intense than that found elsewhere in the brain, i.e., in the opposite 
 hemisphere, at the base of the brain, and in the central ganglia. 
 Figs. 44 and 45 represent lesions in the cortex of the side opposite 
 to the injection from a case which appeared, clinically, to be one 
 of cerebral paralysis (monkey No. 27, cf. p. 53). 
 
 The outstanding feature is the great degree of involvement of 
 the vessels, while the infiltration of the tissues is only slight. 
 
 Fig. 44. 
 
 Marked infiltration of the vessels of the cerebral cortex of monkey No. 27, 
 with slight general infiltration. 
 
 Fig. 47 shows one of the infiltrated vessels in fig. 44 under a higher 
 magnification. 
 
 The distribution of the areas is very irregular in the brain, as 
 in the medulla. They are far apart and the component round cells 
 are not numerous or closely massed together in the infiltrations of 
 the tissues. It is remarkable that in many cases, where inoculation 
 was performed by the intracerebral method, no trace of lesions in 
 the brain could be found. 
 
 I did not investigate the cerebellum. In man, lesions similar 
 to those in the cerebrum are found. Neither was I able to give 
 much attention to the character of the cells forming the infiltrations. 
 As far as I can judge, Wickman's interpretation applies equally well 
 to the appearances found in monkeys. It is well known that there 
 
PATHOLOGY AND PATHOGENESIS 1 23 
 
 has been much controversy as to whether these cells are leucocytes 
 or are derived from the fixed tissue elements. Apart from a few 
 polymorphonuclear leucocytes, Wickman considers the cells to be 
 lymphocytes or lymphocytes which have undergone further develop- 
 ment. We were able to demonstrate very clearly that the process 
 is a different one from that which occurs in true suppurative inflam- 
 mation, in the course of the examination of those monkeys in which 
 a secondary infection had unfortunately taken place at the site of 
 inoculation. The cells which Wickman regarded as being derived 
 from lymphocytes are similar to the " polyblasts " of Maximow. 
 Instead of the round nucleus with much chomatin and the small 
 amount of cytoplasm which characterize the true lymphocyte, these 
 cells have a nucleus which is lighter in colour, contains less chroma- 
 tin, is not quite round but slightly folded, and a wider margin of 
 cytoplasm. Wickman found cells in all stages intermediate between 
 the true lymphocyte and the polyblast, and concluded therefore that 
 
 4 
 
 A- 
 
 \v- 
 
 
 Fig. 45. 
 
 Infiltrated vessel in the cortex of monkey No. 27 (from the side opposite 
 to that on which the injection was made). 
 
 the latter is a derivative of the former. The polyblasts are specially 
 numerous in tissue infiltrations; in the infiltrated vessels and pia 
 mater the true lymphocyte predominate (vide fig. 22). In neurono- 
 phagy many polymorphonuclear leucocytes as well as polyblasts are 
 seen, but Wickman considers that the latter alone act as phagocytes. 
 
 As the appearances found in man in the pia mater, spinal cord, 
 medulla, brain, &c, correspond almost exactly with those found in 
 the monkey, it is unnecessary to describe them in detail. I refer 
 the reader to Wickman' s description. 
 
 In man and in the monkey, therefore, the so-called poliomyelitis 
 has been shown to be a non-suppurative, infiltrative inflammatory 
 process of a lymphocytic type, which may affect the pia mater or any 
 other part of the central nervous system in a disseminated manner, 
 although it tends to involve the grey matter, and, in particular, the 
 anterior horns 
 
124 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 Fig. 46. 
 Infiltration into the tissues of the brain of monkey Xo. 27. 
 
 • 1 rJ*2^sS 
 
 
 Fig. 47. 
 Infiltration of a vessel (one of those seen in fig. 44). 
 
PATHOLOGY AND PATHOGENESIS 
 
 I2 : 
 
 The Stage Of Repair.— I was able to study this stage in only 
 one instance. Most of the monkeys which became paralysed died 
 in a few days, and even those which survived the first few days 
 died shortly afterwards with symptoms of marasmus. The sole excep- 
 tion to this was monkey Xo. t>7, which was inoculated on March 2, 
 1910. Paralysis set in on the 9th, and speedily became complete in 
 the hind limbs. The monkey died (for details see p. 57) on April 14, 
 forty-three days after inoculation and thirty-six days after the onset 
 
 / 
 
 Fig. 48. 
 
 The greater part of the left half of the spinal cord of monkey No. 37. 
 area is seen at the apex of the left anterior horn. 
 
 An 
 
 of paralysis. The brain was not examined. No lesions were found 
 in the medulla, the cervical or the dorsal regions; in the lumbar 
 region almost symmetrical lesions were present, as shown in 
 fig. 48, although the magnification is low. 
 
 Under a higher power the lesion is seen to involve the greater 
 part of the anterior horn (.fig. 49), particularly in its lateral part. 
 
126 EPIDEMIC INFANTILE PARALYSIS 
 
 There is considerable rarefaction of the stroma, the wide meshes of 
 which are filled by a fine network containing" small collections oi 
 round cells. Ganglion cells are almost entirely absent; it is remark- 
 able that one v/ell preserved cell was found in the middle of the 
 lesion. I have been unable to find any proliferation of the blood- 
 vessels, as has been described in this stage by several authors. In 
 fig. 49 an infiltrated vessel may be seen. After thirty-six days,, 
 therefore, a considerable lesion was still present in the anterior 
 horns, but nothing of the nature of scar tissue. Judging by the 
 clinical history of the acute stage of the illness, and by the appear- 
 ances found in other monkeys, it is very probable that other and 
 more widespread lesions were present at first, which had disappeared 
 with the exception of those in the anterior horns. It may be that 
 
 r? ; 3» 
 
 :--6l 
 
 Fig. 49. 
 
 The anterior horn in fig. 48 under a higher power. Chronic changes ; 
 rarefaction of the stroma; increased number of cells; to the right a blood- 
 vessel with infiltrated walls ; marked destruction of the ganglion cells. 
 Below and to the left of the centre, a well preserved ganglion cell. 
 
 the peculiar liability to the disease of this part of the spinal cord 
 is shown better in these chronic cases. Levaditi and Stanesco found 
 scar tissue and proliferation of the blood-vessels in monkeys which 
 died sixty-seven days after the onset of paralysis. 
 
 According to the more exact descriptions of the stage of repair 
 in man, particularly in those given by Wickman, the lesions are 
 characterized by the presence of cells containing fat granules; such 
 cells are met with frequently in lesions of the nervous system, they 
 are associated with degeneration of the nervous elements and are 
 found close to blood-vessels. The glia cells are increased in 
 number in the later stages of repair. It has been shown during this. 
 
PATHOLOGY AND PATHOGENESIS 1 27 
 
 stage that the process is not limited to the anterior horns, but takes 
 place extensively in Clarke's column and in the posterior horns. 
 Degeneration of the tracts and of the anterior roots has been 
 demonstrated by means of suitable methods. 
 
 In all the monkeys which recovered completely from the 
 paralysis we were unable to find any lesions. It is true that these 
 monkeys were only killed some months after inoculation and several 
 weeks after all paralysis had disappeared. Monkeys which were 
 reinfected without any result after they had recovered from 
 paralysis showed no microscopical lesions, even when they 
 were examined only a short time after reinfection (in one case 
 eighteen days). 
 
 I will mention here certain observations which have been made 
 on monkeys killed or dying during the stage of incubation. In my 
 own series there are two such cases. Monkey No. 22 received an in- 
 jection simultaneously into the brain and peritoneum on January 18, 
 1910; it died of gastro-enteritis on the 24th before any paralysis had 
 appeared. The monkey used as a control became paralysed on the 
 tenth day. Microscopical examination revealed purely normal con- 
 ditions. 
 
 Monkey Xo. 62 died four days after infection; the control 
 became paralysed on the ninth day. Xo lesions were found in the 
 spinal cord. 
 
 Landsteiner and Levaditi had a similar experience with four 
 monkeys which received intracerebral and intraperitoneal injections 
 on the same day. Three were killed on the second, fourth, and 
 seventh days respectively. The fourth became paralysed on 
 the eleventh day. The central nervous system of the first 
 three was found normal except that there was a slight traumatic 
 inflammation of the meninges in the case of the two killed on the 
 second and fourth days. 
 
 In the light of these experiments it seems clear that lesions 
 occur only just before the onset of paralysis. The experience of 
 Leiner and v. Wiesner was somewhat different; they found changes 
 in the spinal cord (hypersemia, small haemorrhages, degeneration of 
 the g _ anglion cells) on the third day after infection; the control 
 became paralysed on the eighth day. Whether the lesions, which 
 were not quite typical, were really due to the virus cannot be stated 
 with certainty. Further injections made with material from this 
 spinal cord into other monkeys w T ere not successful. The cord of a 
 monkey killed on the fifth day was proved to contain virus. 
 
 The Final Stage. — This, the stage of scar formation, I have 
 not been able to observe from reasons which I have given above. 
 In man a scar occupies the anterior horns usually, and makes them 
 appear diminished in size. Under the microscope this scar appears 
 to be composed of fibrillar sclerotic tissue with no nervous elements. 
 In other cases the only change seen is atrophy of the ganglion 
 cells; Charcot's theory of a primary cell lesion was probably based 
 on such cases. The blood-vessels are thickened in the sclerotic 
 
128 EPIDEMIC INFANTILE PARALYSIS 
 
 areas. The anterolateral tracts show some degeneration; much 
 importance was attached to this change by the earlier investigators 
 whose attention was thus turned away from the more important 
 lesions. This degeneration of the lateral tract must not be regarded 
 as evidence that the process had invaded the white matter, but as 
 an endogenous degeneration. It is seen at levels where the grey 
 matter is normal. In rare instances it may be due to small lesions 
 in the white matter. Degeneration and atrophy of the peripheral 
 nerves and muscles are present. Finally, there are traces of atrophy 
 in the cerebral motor area; this is probably a secondary result of 
 the destruction of the lower motor neuron. Wickman, however, 
 has reminded us that the effect of the cerebral lesions must not be 
 overlooked, and our experience with monkeys has shown that 
 lesions are specially liable to occur in the central convolutions. 
 
 Poliomyelitis in Adults, Landry's Paralysis, Polyneuritis, 
 Rabies and Borna's Disease in their Relation to Heine-Medin 
 Disease. — I have already mentioned the important contributions to 
 our knowledge of the nature of Heine-Medin disease which have 
 resulted from the investigations into the pathology of the disease 
 by Wickman and others. Wickman was the first to demonstrate 
 afresh the complete identity of poliomyelitis in adults and infantile 
 poliomyelitis; he showed that Landry's paralysis and poliomyelitis 
 acuta are identical from the point of view of their pathology, and 
 produced evidence which made it probable that their etiology is the 
 same also. By means of a critical analysis he showed that in many 
 instances, from purely clinical reasons, the term polyneuritis is 
 used for cases which are caused de facto by a poliomyelitis. The 
 clinical symptoms (parsesthesiae, pains, &c.J can be explained by a 
 poliomyelitic lesion, and the good prognosis which attaches to 
 " polyneuritis " is not incompatible with a poliomyelitic process. 
 As Striimpell suggested a long time ago, Wickman considers that 
 the differentiation between polyneuritis and poliomyelitis is more or 
 less artificial. In Chapter II we have seen how important a recog- 
 nition of this fact is for clinical work. 
 
 Wickman 's observations on the similarity of the pathological 
 picture in poliomyelitis and rabies has shown the way in regard to 
 studies into the etiology of Heine-Aledin disease. The pathological 
 process in rabies is a disseminated, infiltrative myelitis, which shows 
 a preference for attacking the blood-vessels and particularly the 
 anterior horns. 
 
 Again, Joest and Degen have shown that the so-called Borna's 
 disease in horses presents an almost complete pathological analogy 
 to Heine-Medin disease in man. In that disease they found a dis- 
 seminated, infiltrative meningo-myelo-encephalitis of a lvmphocytic 
 type, which specially affected the blood-vessels. The only difference 
 between it and infantile paralysis lies in the fact that it tends rather 
 to involve the brain, by preference the olfactory lobe. But it also 
 affects the rest of the central nervous system, and in the spinal cord 
 the anterior horns are a favourite situation. In other particulars 
 
PATHOLOGY AND PATHOGENESIS 1 29 
 
 the pathological features are very similar (slight macroscopic 
 changes, involvement of the meninges, relation to the blood-vessels, 
 the condition of the cerebrospinal fluid). I have already mentioned 
 the bodies which Joest and Degen found in the ganglion cells, and 
 which they regard as specific to Borna's disease. It would be not 
 uninteresting to investigate {e.g., by means of serum diagnosis) the 
 biological relationship between the virus of Heine- Aledin disease 
 and that of Borna's disease. I stated in Chapter III that horses 
 are not susceptible to the virus of Heine-Aledin disease. 
 
 IV PATHOGENESIS. 
 
 In the first section of this chapter I gave a summary of the 
 historical aspect of the pathology and pathogenesis of the disease; 
 I also formulated four questions. Having sketched the progress 
 which has been made by experiments on animals, I will attempt to 
 provide answers to these questions. 
 
 The Point of Attack of the Virus. — At what point in the central 
 nervous system does the virus first have an effect ? Controversy has 
 raged around the question whether the ganglion cell is affected 
 primarily, as Charcot believed, or whether the first change is an 
 interstitial one, according to the suggestion made by Roger and 
 Damaschino. Such a controversy is perfectly natural. On the 
 one hand, Charcot's theory explained the clinical symptoms which 
 in great part point to a purely motor paralysis. Such a selective 
 action of the virus was not a new idea; we were accustomed to it in 
 the case of tetanus. On the other hand, pathological investigation 
 showed not only that the lesion was not purely degenerative, but 
 that it was by no means confined to the motor regions of the cord. 
 In that case how was the motor character of the paralysis to be 
 explained ? Further , accepting the fact that the pathological pro- 
 cess mainly affected the motor regions, why should a virus which 
 acted by producing disseminated lesions show this preference for 
 the anterior horns ? 
 
 Keeping to the microscopical appearances, the interstitial 
 character of the process appears to be very well marked. The 
 involvement of the blood-vessels is so striking that in many cases 
 one may say that the distribution of the lesions depends mainly upon 
 the vascular supply and particularly upon the situation of the veins. 
 The question arises, whether the disease of the vessels may not be 
 explained by some pathological process affecting the ganglion cells 
 or glia, and secondarily acting as an irritant to the vessels, causing 
 emigration of the lymphocytes. In such a case, an accumulation of 
 lymphocytes around the blood-vessels would be a natural sequence. 
 Against this view, however, the observations made by Wickman 
 and ourselves on the kind of vessel involved are of much importance. 
 According to the theory, the smallest vessels, the capillaries, should 
 be the most affected, but we find it to be the veins. Further, well 
 preserved ganglion cells are often seen in the middle of a markedlv 
 
 9 
 
I30 EPIDEMIC INFANTILE PARALYSIS 
 
 infiltrated area and even quite close to veins which are severely 
 affected. There is little justification for supposing" that the cells 
 are really damaged, but that this cannot be seen, because slight 
 changes in the cells are so easily recognized. It is therefore impos- 
 sible to believe that the involvement of the vessels is secondary to 
 an affection of the nervous elements. The finding of infiltrated 
 vessels in the middle of the white matter, at a distance from the 
 grey matter, is another argument for the primary nature of the 
 lesion in the vessels; so also is the presence of lesions in the pia 
 mater, particularly when they are found on the posterior aspect 
 of the cord, far from the grey matter, and at levels in the cord 
 where the grey matter is scarcely involved at all. Everything 
 points to the change in the vessels being largely independent of 
 changes in the nervous elements; there is no doubt that in at any 
 rate very many places we arc justified in considering tlic lesion to be 
 primarily vascular or perivascular. 
 
 But this does not mean that the virus attacks the vessels alone 
 and has no direct effect upon the ganglion cells. The general 
 impression is that the changes in the ganglion cells are of a secon- 
 dary nature; it may be that the infiltrative process extends directly 
 from the vessels to the ganglion cells, or that the cells succumb to 
 nutritional disturbances resulting from the diseased condition of the 
 vessels or from the oedema. The argument drawn from clinical 
 experience, that the occurrence of paralysis so suddenly can be 
 explained only by a primary affection of the ganglion cells, cannot 
 be maintained; the experiments on monkeys have shown that inter- 
 stitial change is very considerable in those cases where paralysis 
 sets in suddenly and rapidly causes death. Demonstrable lesions in 
 the interstitial tissues may occur therefore quite as rapidly as in the 
 parenchyma. I again call particular attention to the absence of any 
 lesion shortly before the onset of paralysis in monkeys. Some- 
 times, it is true, the ganglion cells appear to be the only structures 
 involved ; but in my opinion enough importance is not attached to 
 the oedema which is frequently present in such cases. One fact 
 proves conclusively that primary affection of the ganglion cells may 
 occur; that is the neuronophagy which is seen in the most acute cases. 
 Although here interstitial changes are by no means absent, yet the 
 isolated cells surrounded by round cells give the impression of a 
 localization of the damage to the ganglion cell. Landsteiner and 
 Levaditi observed degenerative change in the cells before the 
 occurrence of neuronophagy, but I was unable to find it. I believe 
 that this type of alteration in the cell is not followed by neurono- 
 phagy and is caused indirectly. I saw quite normal cells surrounded 
 by lymphocytes. Nor could I convince myself that the interstitial 
 changes were preceded by recognizable alterations in the ganglion 
 cells, as has been reported by Landsteiner and Levaditi. and on 
 which they base their argument that the process always begins in 
 the ganglion cells. [They quite recognize that the changes in the 
 vessels and the pia may appear independently.] On the contrary, I 
 
PATHOLOGY AND PATHOGENESIS 131 
 
 have frequently seen well preserved ganglion cells lying within the 
 infiltrated areas. In the atypical (marantic) forms of the disease 
 Leiner and v. Wiesner found no cell infiltration but hyperaemia, 
 haemorrhages and degeneration of the ganglion cells. In discussing 
 the pathogenesis of the typical, paralytic form of the disease it 
 seems to me to be an important observation that the non-paralytic 
 form presents appearances indicative of essential involvement of the 
 ganglion cells. 
 
 The general conclusion arrived at is this : The process is mainly 
 primarily interstitial; the ganglion cells are affected primarily in 
 some degree, but this is small compared with the interstitial change. 
 Our position is the same as that taken up by Fr. Schultze many 
 years ago on the basis of histological and critical studies. 
 
 Having arrived at this point, as Wickman rightly says, the 
 •difficulty in explaining the clinical symptoms really begins. One 
 would expect from the microscopical appearances to find the clinical 
 picture of a transverse myelitis; instead of which the symptoma- 
 tology is that of a system disease of the spinal cord. The in- 
 congruity between the symptoms and the pathological findings has 
 .given much trouble to the adherents of the primary vascular theory. 
 Many hypotheses have been suggested, which all depend upon some 
 -cause outside the nervous parenchyma to explain the peculiar 
 susceptibility of the anterior horns. This liability of the anterior 
 horns is a fact admitting of no doubt. A point of special import- 
 ance arising out of the experimental work is the fact that in mon- 
 keys which were inoculated intracerebrally the favourite situation 
 of the pathological process was in the grey matter of the anterior 
 horns of the spinal cord; the symptoms were mainly those of a 
 flaccid motor paralysis, usually of the hind limbs, and so, in spite 
 of the abnormal, artificial point of entry of the virus, the appear- 
 ances presented by human " spinal " paralysis were reproduced 
 with considerable fidelity. How can this be explained ? 
 
 In view of the special involvement of the blood-vessels it has 
 heen suggested that peculiarities of the vascular supply are the 
 ■cause of the remarkable vulnerability displayed by the anterior 
 horns. The area of distribution of the anterior spinal artery was 
 said to be particularly liable; Kadyis had shown that it supplied 
 the anterior horns by branches which passed into the cord at the 
 "bottom of the anterior longitudinal fissure and then turned out- 
 wards. Pierre Marie stated in consequence of this, that the whole 
 process was one of embolism of the anterior spinal artery. Wick- 
 man has shown that this supposition is certainly incorrect. Apart 
 from the fact that no embolism or thrombosis is found in the vessel 
 the character of the lesion does not suggest that it is of embolic 
 origin; no necrosis is seen. Again, embolism artificially produced 
 shows no tendency to affect the grey matter more than any other 
 part. Further, it has been seen that not the arteries but the veins 
 are the more affected and, finally, the process is by no means 
 confined to the central regions of the cord; the peripheral portions 
 
I32 EPIDEMIC INFANTILE PARALYSIS 
 
 are hardly less affected. For these and other reasons the theory 
 of embolism must be rejected, and no cause operating" by way of 
 the anterior spinal artery alone can be accepted. Wickman's theory 
 is worthy of more consideration; he associates together the vulner- 
 ability and the vascularity of the different parts of the cord. The 
 greater the blood supply is, the more intense the pathological 
 process. When the arrangement of vessels changes the localization 
 of the lesions is found to change also; in the lower lumbar regions 
 the lesions are found mainly in the anterior horns, but in the upper 
 lumbar and lower dorsal regions the process is more in the region 
 of Clarke's column, which at this level is much more richly supplied 
 with blood-vessels. I shall return later to certain difficulties which 
 even Wickman's theory does not explain. 
 
 The Spread of the Virus within the Central Nervous System. — 
 The microscopical appearances indicate that the vessels constitute 
 the main channel along which the virus spreads. Wickman holds 
 that the clinical symptoms contra-indicate this route; there is a 
 certain regularity in the way the paralysis spreads which indicates 
 that the pathological process underlying it is advancing in a con- 
 tinuous if rapid manner. This continuity of spread of the lesion 
 is shown in microscopical sections (compare the photographs of 
 longitudinal sections), and leads one to suspect the lymph channels. 
 Experimental studies have shown that the virus has a special affinity 
 to the lymphatics, and Wickman has shown that in the central 
 nervous system the blood-vessels are surrounded by perivascular 
 lymph channels in which the first signs of a lesion appear. Further, 
 the lymph channels which lie in the nervous matter itself must be 
 considered. Some of the observations made on monkeys have a 
 bearing on this point; after intracerebral inoculation into the central 
 convolutions on one side, the paralysis appeared usually on the 
 contralateral side. This leads me to the difficult question of ex- 
 plaining how it is that monkeys when inoculated into the brain 
 suffer subsequently from paralysis which is mainly spinal. I 
 imagine that the virus passes along the perineural lymph spaces 
 as well as the perivascular ones; on reaching certain regions in 
 the spinal cord which are richly supplied with lymph (the grey 
 anterior horns) it finds there a particularly suitable soil. The 
 objection, that there is plenty of opportunity for the virus to 
 develop in the brain itself, is not justifiable; in the first place, 
 cerebral lesions are certainly more common in monkeys which have 
 received an intracerebral inoculation than in man; in the second 
 place, the motor cells in the brain have not the same close relation 
 to the blood-vessels which is found within the narrow limits of 
 the spinal cord, with its complex network of vessels. While I 
 agree with Wickman that richness in vascular and lymphatic supply 
 causes the peculiar liability of the anterior horns, I am inclined to 
 explain the predominance of spinal symptoms in monkeys which 
 have received intracerebral inoculation by the direct passag'e of 
 the virus along the perineural lymph spaces down to the anterior 
 
PATHOLOGY AND PATHOGENESIS 1 33 
 
 horn of the opposite side, where it finds a soil suitable for its 
 further development. Joest's observations on Borna's disease lend 
 some support to this view; he found the most severe lesions in 
 the olfactory lobe and connects this with the entrance of the virus 
 through the nose. In Borna's disease the virus spreads along" the 
 perivascular and perineural lymphatics, and finally becomes localized 
 in the anterior horns of the grey matter of the cord. 
 
 In short, the virus spreads along the lymph channels in the 
 central nervous system, along those which surround the vessels 
 as zvell as those running in the substance of the brain and spinal 
 cord. The virus develops more freely zvherever there is a rich 
 supply of lymph. 
 
 Hoche assumes that the central canal serves as a channel for 
 the virus. His theory is founded upon experimental evidence, and 
 he considers that the patency of the canal in children is the cause 
 of the frequency with which they suffer from the disease. This 
 explanation cannot be accepted. In the first place, the poliomyelitis 
 of adults, in whom the central canal is closed, is quite similar to 
 that of children, and in the second place the central canal is only 
 rarely involved in human beings and never in monkeys, according 
 to my own experience. 
 
 The Route by which the Virus reaches the Spinal Cord. — 
 At first sight, considering how extensively the vessels are affected, 
 it seems as though the virus must have been brought to the cord 
 by the blood-stream. However, Wickman has shown that it is not 
 the capillaries, as one would expect in such a case, but the veins 
 which are principally, and sometimes exclusively, involved. That 
 the blood and the organs rich in blood contain no virus, or at most 
 the minutest quantity, is strong evidence against the theory of 
 hematogenous infection. Virus has never been found in the blood 
 during the stage of incubation. The following observation made 
 by Renault is further evidence against this possible method of 
 transmission of the virus : A pregnant woman had a severe attack 
 of poliomyelitis, recovered, went to term and bore a healthy child 
 with no signs of paralysis. As the virus is capable of passing 
 through the most perfect filters known, one would expect that it 
 would be transmitted to the foetus, if it circulated in the blood- 
 stream. It has been clearly shown by experiment, that inoculation 
 into nerves is commonly successful, the virus passing up within 
 the nerve to the spinal cord and causing paralysis of the muscles 
 supplied by that nerve. Further, it has been demonstrated that 
 there is a definite relationship between the situation chosen for 
 inoculation and the part of the spinal cord which is first affected; 
 the virus always chooses the shortest way to the cord, i.e., the path 
 of the nerves. 
 
 On page ioo I have shown that the occasional success attending 
 intravenous inoculation does not contradict the theory of trans- 
 mission by the nerves. Consequently the conditions are almost 
 exactly those which obtain in the case of rabies. [Some authors 
 
134 EPIDEMIC INFANTILE PARALYSIS 
 
 recently have revived the hematogenous theory for rabies, on the 
 ground that the lesions first observed are vascular in type; the 
 above critical analysis makes it clear that this is no valid argument 
 in favour of transmission by the blood-stream.] 
 
 Harbitz and Scheel, as well as Flexner, accept the suggestion 
 made by Schultze a long time ago, that the virus first settles in 
 the meninges and then causes the lesions in the cord by direct 
 extension of the meningitic lesion. According to our views, it is 
 quite possible and probable that the virus, proceeding along the 
 nerves, first reaches the pia mater and gives rise to lesions in it. 
 But that the spinal cord is affected only directly from the meninges 
 seems to us, as it does to Wickman, exceedingly unlikely; there 
 is no exact correspondence between the lesions in the pia and those 
 in the cord, and the pia in the depths of the anterior fissure is 
 usually more affected than that covering the exterior of the cord. 
 It is by no means rare to find the infiltration of the fold of pia 
 cease when the pia reaches the surface of the cord. If we bear 
 in mind the knowledge gained from experiments, that the virus 
 tends to follow the lymph-stream, we shall not be far wrong in 
 saying that the virus of Heine-Medin disease travels centripetally 
 in the lymphatics lying round and in the peripheral nerves until it 
 readies tJie central nervous system, where it attacks the pia mater 
 and simultaneously gains entrance into the cord along the spinal 
 roots. 
 
 Joest's observations on Borna's disease in horses give valuable 
 support to this view. After a most careful consideration of all 
 the probable paths along which the virus could travel he arrives 
 at the conclusion that the active agent reaches the brain by way 
 of the interstices and the sheath of the nerves. In Borna's disease 
 infection begins in the nasal mucous membrane ; hence the early 
 and intense involvement of the olfactory lobe. The virus passes 
 in a centripetal direction to the subarachnoid space, causes a certain 
 amount of meningeal irritation, and then passes along the nerve 
 into the brain. Joest denies that the further extension of the 
 process within the central nervous system is due to direct involve- 
 ment from the pia mater. 
 
 The Portal of Entry of the Virus. — The initial symptoms of 
 the disease point to the mouth and throat and the respiratory tract 
 or to the alimentary tract as the situations where the virus enters 
 the body. The occurrence of lesions, which are clearly due to the 
 virus, in the gastro-intestinal tract after inoculation by any method 
 and the appearance of the virus in the mucous membrane of the 
 throat under the same condiions, lead one to believe that these 
 symptoms are the result of a secondary inoculation with the virus. 
 But since these symptoms almost invariably precede an attack of 
 Heine-Medin disease in human beings, I cannot but think that they 
 are symptoms of primary infection. The experimental results do 
 not put these situations out of court as points of entry of the virus, 
 although it is not easy to produce infection by these routes. In 
 
PATHOLOGY AND PATHOGENESIS 135 
 
 consideration of the known predilection of the virus for lymphatic 
 tissue, it is quite probable that the mucous membranes of the throat 
 and of the intestinal canal constitute the chief portals of entry of 
 the virus because they are so richly provided with lymphatics. It 
 is difficult to say which of the two is the more common portal. 
 Different epidemics differ in this respect. If our theory is correct, 
 that the virus always takes the shortest route to the central nervous 
 system, we are inclined to consider the gastrointestinal tract as 
 the main point of entry, because the large majority of cases are 
 affected in the lower limbs. The fact that the lower limbs are 
 usually affected, wherever inoculation has taken place, must not be 
 ignored. In future, therefore, it will be of the greatest importance 
 to notice carefully where paralysis first shows itself. Particularly 
 it must be noted whether cases, which have symptoms first in the 
 mouth and throat, develop paralysis first in the upper limbs. It 
 would not be remarkable if such cases ultimately were affected in 
 the lower limbs more than in the upper, because we know that the 
 segments of the spinal cord which correspond to the lower limbs 
 are so much more easily affected than the rest of the segments. 
 It is improbable that the virus often enters through the nasal 
 mucous membrane, because the cerebral forms of the disease are 
 rare. 
 
 Conclusions. — None of the deductions we have drawn can be 
 considered conclusive. In the natural sciences it is rare to find 
 a certainty. Many steps in our arguments are based on hypotheses. 
 The following is the most probable of all the theories advanced 
 to explain the pathogenesis of the disease. 
 
 The virus enters the body by way of the lymphatics of the 
 throat or of the intestinal tract, or of both (this varies in different 
 epidemics). Thence it passes in the lymphatics within or around 
 the peripheral nerves to the spinal cord. Here it causes slight 
 infiltrative inflammation of the pia mater, and then enters the cord 
 along- the spinal roots. It spreads within the cord chiefly along 
 the lymph spaces round the veins, but also in those lying in the 
 nervous tissues themselves. It develops freely in parts of the 
 cord, such as the anterior horns of the grey matter, in which the 
 vascular and consequently the lymph supply is rich and where the 
 texture of the tissues is loose. Here the virus gives rise to in- 
 filtrative inflammation of the lymphocytic type, which causes 
 degeneration and destruction of the ganglion cells either by inter- 
 ference with the nutrition of the cells, or by direct involvement 
 in the infiltrative process. In other cases, particularly those in 
 which the process is very acute, the ganglion cells are affected 
 primarily, the cells being always destroyed by the action of 
 phagocytes which are usually lymphocytes. 
 
CHAPTER V. 
 
 Epidemiology. 
 
 I.— HISTORY OF THE EPIDEMICS. 
 
 Early Reports.— The disease has certainly existed for a very- 
 long" time. Heine mentions patients who had suffered from the 
 disease more than fifty years before his time; he says that the 
 disease " is not rare " and quotes an author, Shaw, who met with 
 it in India, Egypt, and other extra-European countries. " Another 
 author, Colman," writes Heine, "' even mentions an epidemic." 
 Wickman considers that this latter statement requires considerable 
 reservation; an author named Colmer (not Colman) reported that 
 he had heard from the mother of a child suffering from hemiplegia, 
 that several cases of hemiplegia and paraplegia in children had 
 occurred in the district within a space of three or four months. 
 The report therefore contains little that is of value as evidence. 
 
 It is curious that the older literature contains not a single 
 reference to any epidemic, although infantile paralysis most cer- 
 tainly occurred. After the appearance of Heine's monographs, and 
 at a time when the literature of the disease was becoming extensive, 
 no mention was made of any epidemic before 1880. It may have 
 been because small groups of cases were not recognized as such, 
 owing to the infectivity of the disease being unknown, or because 
 the clinical differences between the cases caused them to be 
 regarded as examples of different diseases. But when the sym- 
 ptomatology of the commonest type of the disease had been fully 
 described under the name of spinal " infantile paralysis," the 
 absence of reports of epidemics can be explained only by the fact 
 that such epidemics did not occur before 1880. 
 
 The Scandinavian authors were the first to draw attention to 
 the epidemic occurrence of the disease. At about the same time 
 reports were received from other countries concerning groups of 
 cases and the occurrence of several cases in one family. The 
 following is a short summary of the epidemics recorded in the 
 different countries. 
 
 Sweden and Norway. — These two countries dispute one 
 another's claim to priority in the matter of recording the first 
 epidemic. Xetter states that a Norwegian author, Ch. Bull, 
 
EPIDEMIOLOGY 137 
 
 recorded a small epidemic of fourteen cases, four of which were 
 fatal, in the year 1868; Bull is said to have called the disease 
 "meningitis spinalis acuta," but to have described it so that there 
 can be no doubt of its being infantile paralysis. Unfortunately I 
 have not been able to read the report. The epidemic lasted from 
 May to August, and reached its climax in July, when eight cases 
 occurred. According to Wickman, the Swedish physician Bergen- 
 holtz was the first to report an epidemic in 1881 ; he described 
 eighteen cases from Umea in the north of Sweden. In this case 
 there is no doubt of the disease being Heine-Medin disease. The 
 epidemic remained unknown, as the report was only sent to the 
 local health authorities. The observations of Oxholm (Norway) 
 and Cordier (France) also passed unnoticed; they include some state- 
 ments pointing to an epidemic outbreak of the disease. 
 
 Medin first made widely known the epidemic which he observed. 
 He published his exhaustive clinical studies on forty-three cases 
 which occurred in and near Stockholm during the months May to 
 November, 1887, and on twenty-one cases which came under his 
 notice in 1895. The subsequent epidemics in Sweden were studied 
 very thoroughly. Wickman obtained unexampled experience 
 during the epidemics of 1899 (fifty-four cases in Stockholm), 1903 
 (twenty cases in Goteborg), and 1905-1906 (about 1,100 cases spread 
 over a great part of Sweden). His description has become a classic. 
 During the years 1907 and 1908 many more cases were reported 
 from Sweden. 
 
 Oxholm observed a small epidemic of five cases in 1886. It is 
 doubtful if he recognized the true nature of the disease. In the 
 same year Leeg'.aard reported a small epidemic in Mandal, a small 
 Norwegian town. In 1893 Bulow-Hansen and Harbitz made a 
 careful pathological examination of three cases which occurred in 
 one family. Looft observed a small epidemic in 1898-99 in Bergen. 
 The first large epidemic in Norway took place from July to October, 
 1899, fifty-four cases in Bratsberg-, which were studied by Leegaard. 
 On this occasion he made the remarkable discovery that the 
 infection spread along the lines of traffic. In 1904 Nannestad 
 examined forty-one cases and Platou twenty-four. 
 
 Finally, at the same time as the great Swedish epidemic, about 
 1,000 cases occurred in Norway in 1905-06 (Leegaard, Harbitz and 
 Scheel, Geirsvold, &c). 
 
 Assuming that earlier epidemics had not occurred unnoticed, a 
 gradual increase is found, from 1880 onwards, in Scandinavia. At 
 first only small groups of cases, some in families, were noticed, then 
 small endemic outbreaks, later a true epidemic in Sweden in 1887, 
 still later a larger epidemic in both countries in 1899, and. finally, 
 a big epidemic over a great part of Scandinavia in 1905. In propor- 
 tion to the population this was certainly the most serious epidemic. 
 The progress of the epidemics is comparable to that of the North 
 American prairie fires, which begin with a small outbreak, spread 
 insidiously, and finally burst into a mighty conflagration. 
 
ISO EPIDEMIC INFANTILE PARALYSIS 
 
 Germany. — The epidemics in Germany have followed on similar 
 lines. 
 
 In 1882, Mobius and Sanger saw a brother and sister, one of 
 whom suffered from the spinal, and the other from the cerebral 
 form of the disease. 
 
 Striimpell observed three cases in one month in 1886; two of 
 the cases were brother and sister, which lent support to his theory 
 that the disease was infectious. Two further reports were due to 
 the influence of Strumpell's theory. Briegleb in 1890 published 
 live cases which occurred close together near Jena within a period 
 of four weeks. Briegleb published these cases " because they seem 
 to support Strumpell's theory, that a disease which makes its 
 appearance in several places in the same neighbourhood and at the 
 same time is probably caused by some organized morbid agent." 
 The paper by Pleuss is very similar; in 1897 he observed four cases 
 in the neighbourhood of Kiel within three months. Hoffmann in 
 1904 observed a small familial group of cases in Dusseldorf. A 
 brother and sister became ill on the same day; the six-year-old boy 
 suffered from a cerebral hemiplegia, the four-year-old sister from 
 spinal paralysis. Up to this time only small groups of cases had 
 occurred in Germany. 
 
 But matters seemed to be becoming serious when Auerbach 
 reported no fewer than fifteen cases in the months May to Decem- 
 ber, 1898, in Frankfurt alone. The number was large when one 
 considers that from 1892 to 1897 Auerbach had met with only eleven 
 cases. The groups of cases reported in 1908 were larger, one 
 occurred near Heidelberg (thirty-six cases — Hoffmann), one near 
 Hamburg (twenty-two cases — Nonne). These small epidemics 
 proved to be the forerunners of the great epidemic of 1909 in 
 Germany. This mainly affected Westphalia and Rheinland, where 
 certainly 700 cases occurred. The epidemic Avas studied by many 
 authors (P. Krause, Meinicke, Grober, Reckzeh, Wollenweber, 
 Gasters, Lasch, Yieten). It then passed on to Hesse-Xassau, 
 where Ed. Miiller saw 130 cases, and used them for his clinical 
 and epidemiological studies. Thirty-four cases in Hanover (Eichel- 
 berg) followed, about fifty cases in Schleswig (O. Forster), and 
 fifty-one cases in Pomerania (PieperJ. At least 1,000 cases 
 occurred in Germany during 1909. It appears from the proceedings 
 of the medical societies of Berlin that further groups of cases 
 occurred near that city towards the end of 1910. The progress of 
 the epidemics was similar to that in Scandinavia, at first only small 
 groups of cases, then small epidemics, and finally a large epidemic. 
 
 Austria. — In 1898, the first year in which infantile paralysis was 
 met with in Germany in a somewhat epidemic form. Zappert and 
 Neurath reported on groups of cases, which " almost constituted an 
 epidemic," in the neighbourhood of Vienna. Forty-two cases were 
 seen during the summer of 1898, chiefly in August and September, 
 while only 129 instances of the disease had been met with during 
 the preceding ten years. During September there were twelve 
 
EPIDEMIOLOGY 139 
 
 cases, a figure larger than the average yearly number for the ten 
 years before. In Austria also this was only a warning of what was 
 to follow. In 1908 there was an epidemic of about 300 cases in 
 Vienna and Lower Austria, which was investigated by Zappert, 
 Xenrath, Frankl-Hochwart, Locker, Lindner and Alally. and many 
 others. The epidemic began in July, and reached its greatest 
 height in September and October. It is of particular historical 
 interest, because it was the occasion on which Landsteiner and 
 Popper successfully transmitted the disease to monkeys. In 1909 
 the epidemic passed on to Upper Austria and the Steiermark ; 
 according to Furntratt and Potpeschnigg, at least 600 cases 
 occurred. Karnten was also affected. Potpeschnigg made the 
 interesting observation that the large epidemic was preceded by 
 several small ones during 1906 and 1907. In Austria, as in the 
 other countries, the same warning is given before the occurrence 
 of a great epidemic. 
 
 Holland and Switzerland. — The other European countries have 
 not suffered from widespread epidemics. Groups of cases have 
 occurred in 1906 and in 1909 in Holland, but no epidemic. During" 
 1909 there were twenty-four cases in Leyden, and fourteen cases 
 in Warnsweld and Zutphen. During 1910 cases occurring in groups 
 were observed in Switzerland by Eichhorst and Hagenbach. 
 
 England. — There are few reports from England. The experi- 
 ence of Pasteur in 1896 was remarkable. Seven children in one 
 family became ill within ten days: some suffered from the cerebral, 
 some from the spinal form; the others had only indefinite feverish 
 symptoms, and belonged to what we should call now the abortive 
 type. In 1897 Buzzard observed four cases in London, two of 
 which were brother and sister, while two lived in adjacent streets. 
 Batten saw nine cases within six weeks during July and August, 
 1902. In the same year Mitchell Stevens made a similar observation 
 in Cardiff. In 1909 Treves reported a small epidemic in Upminster, 
 and Parker collected thirty-seven cases in Bristol. During 1910 
 outbreaks occurred in Carlisle (thirty-four cases — Beard), Edinburgh 
 (sixty-two cases — Low), Tillycoultry (five cases — Currie and Bram- 
 well). Barrow (thirty-seven cases — Garrow), Maryport (thirteen 
 cases — Garrow), and South Shields (five cases — Mostyn). In 
 191 1 the number of small epidemics was larger. The disease 
 appeared in epidemic form in Huntingdonshire, Hampshire, Stow- 
 market, Derbyshire, Devon. Cornwall and Dorset. In Devon 
 and Cornwall no less than 224 cases occurred within the year 
 (Reece). Thus in England the same phenomenon is seen as in 
 other countries. The small epidemics have become more frequent 
 and involve an increasing number of cases, but so far we have been 
 spared from a large epidemic. The disease was made compulsorily 
 notifiable in London in September, 191 1, and in some provincial 
 centres since then. 
 
 France. — The French observations are not without interest as 
 they are analogous in many respects to those made in Scandinavia, 
 
140 EPIDEMIC INFANTILE PARALYSIS 
 
 Germany, and Austria. Cordier reported thirteen cases in 1888; 
 they were collected after the epidemic in Sainte-Foye d'Argentiere, 
 a villag'e with 1,400 inhabitants near Lyons; there were four fatal 
 cases. Cordiers observations make it probable that in two cases 
 infection could be traced to visits made to patients already ill. The 
 cases occurred largely in adjacent houses. It was at this time that 
 the contagiousness of the disease was indicated. In 1893 Andre 
 saw four cases near to Saint-Girons, and several cases in Toulouse 
 in 1895, in which there was probable infection from neighbours. In 
 the same year Beclere received a reliable report of a dozen cases 
 which occurred within three months in one village. The same 
 author observed the disease in brother and sister in 1898; Guinon 
 and Rist the same in 1903. In the year 1909 there was a definite 
 epidemic of the disease in Paris and its surroundings; Netter states 
 that at least one hundred cases occurred. 
 
 Spain. — Only small epidemics have occurred in Southern 
 Europe. Roset reported a small epidemic of eight cases from the 
 neighbourhood of Vails in 1896; curiously enough five cases were 
 hemiplegic in type. 
 
 Italy. — There are many reports from Italy, but they all concern 
 groups of cases or quite small epidemics (1895, thirteen cases from 
 the surroundings of Padua, observed by Cerevesato ; in the same 
 year seven cases in fifteen days in Montespertoli near Florence, 
 reported by Pieraccini). In 1895, Buccelli saw seventeen cases in 
 Genoa, which all occurred in the same' part of the town, several in 
 one house and in one family. Further observations are those of 
 Fabris (twenty-two cases in the years 1897, 1898 in Conegliano), 
 Simonini (twenty cases in September and October in Vicence), and 
 Lorenzelli (twenty-six in 1901 in Parma). 
 
 Russia. — There is one communication by Jogichess that 
 grouped cases of infantile paralysis occurred in St. Petersburg in 
 the years 1909 and 1910. 
 
 North America. — Great epidemics have occurred in North 
 America, but they were preceded by warning outbreaks in the shape 
 of groups of cases and small endemics. Thirty-eight cases were 
 observed in Massachusetts in 1892. Caverley and Macphail 
 reported an epidemic of 126 cases from Vermont in 1894, which 
 they diagnosed incorrectly as cerebrospinal meningitis. In 1896 
 there were groups of cases in Alabama and Maine. In 1897 H. L. 
 Taylor observed twelve cases in a small district of New York; in 
 1898 M. Taylor saw four cases, two of these were brother and sister 
 and one a cousin of the same. In the same year Newmark and 
 Packard observed the disease in families, in 1899 Chapin saw seven 
 cases in Poughkeepsie, and Mackenzie seventeen cases in Dutchess 
 County, in 1900 Painter thirty-eight cases in Boston, and 
 Bondurand and Woods fifteen cases in Alabama. During 1901, 
 fifty-five cases were reported from San Francisco; in 1906 there were 
 large groups of cases of infantile paralysis in New York (Collins 
 and Romeiser). 
 
EPIDEMIOLOGY 141 
 
 The large American epidemics began in 1907. In New York 
 2,500 cases occurred (Collins, Gibney, Wallace, Romeiser, Koplik, 
 Starr, Berg, Clowe, and others), in Massachusetts there were 234 
 cases, and the disease spread to New Jersey and Connecticut. There 
 was a small epidemic of 136 cases (Lovett and Emerson) in Massa- 
 chusetts in 1908, also in Pennsylvania, Iowa, Wisconsin, Michigan, 
 and Minnesota. The Nebraskan epidemic occurred in 1909, and 
 during these three years (1907-1909) the number of children affected 
 had risen to the considerable total of 20,000. 
 
 Flexner says that few of the States have been spared; the 
 Southern States appear to be free, but this is probably due to faulty 
 reports. Flexner further points out that the epidemic began in the 
 States on the east coast, which receive many emigrants from 
 Scandinavia. 
 
 Cuba. — Lebdreo and Recio reported an epidemic in 1909. 
 
 South America appears to remain free from the disease. 
 
 Australia. — Small epidemics have been reported here and there. 
 In 1895, fourteen cases in Port Lincoln (Alston); in 1904, chiefly 
 during March and April, thirty-four cases in Sydney and Brisbane 
 (Wade); in 1908, 135 cases in Melbourne (Stevens). 
 
 The Origin of the large Epidemics. — The preceding facts lead 
 to the conclusion that it is the northern countries, particularly 
 Scandinavia and North America, which are most attacked by the 
 disease. Large epidemics occurred first in Scandinavia. The 
 occurrence of small epidemics shows that southern countries are 
 by no means immune to this disastrous scourge. It is, perhaps, 
 only a question of time before they are afflicted by a great epidemic. 
 
 We see that all large epidemics are preceded by warning out- 
 breaks in the shape of small groups of cases. It is doubtful there- 
 fore whether the view that Flexner seems to take is correct, that 
 the outbreak of a severe epidemic is determined by the importation 
 of the disease from Scandinavia, although the fact that the 
 Scandinavian epidemics antedated the others seems to give some 
 support to this view. But since the so-called sporadic form of the 
 disease has always been found extensively in each country before 
 the outbreak of an epidemic, and since we know that the sporadic 
 and epidemic forms are identical, there seems to be no conclusive 
 proof that the epidemics in Germany, Austria, and North America 
 have been due to importation of the virus from Scandinavia. It is 
 most remarkable that a disease, which had been well known in its 
 sporadic form for many years, should attack groups of cases in 
 1880 and onwards, and should appear in epidemic form first in 1905. 
 Any attempt to explain this must remain more of less a hypothesis. 
 Some suggest that the cause of the disease became more virulent, 
 and instance, in support of this theory, that fatal cases are more 
 frequent during epidemics and adults are more often attacked than 
 by sporadic poliomyelitis. It is probable that both these statements 
 are incorrect; when there was no epidemic the cause of death was 
 not diagnosed as due to poliomyelitis, nor was the disease diagnosed 
 
142 EPIDEMIC INFANTILE PARALYSIS 
 
 as such in adults before the works of Medin and Wickman became 
 well known. The following is a possible explanation of the sudden 
 appearance of the disease in epidemic form; owing" to a particular 
 chain of causes a group of children becomes affected, and the 
 resultant accumulation of infective material makes a wider dis- 
 tribution of the disease possible. But there still remains the ques- 
 tion why it is only in the last few years that these unknown factors 
 have caused this accumulation of the virus. Possibly, the great 
 increase in the network of railways has resulted in a wider distri- 
 bution of infective material. In truth, we are quite ignorant of 
 the causes which have produced this result, and can only confess 
 the fact. 
 
 II.— THE EPIDEMIOLOGICAL 
 
 CHARACTERISTICS OF THE SEVERAL 
 
 OUTBREAKS. 
 
 Season. — In almost all the outbreaks mentioned above we find 
 certain definite relations between the outbreak of an epidemic and 
 the time of year. The disease is pre-eminently one of the summer 
 and autumn, in particular of the late summer and early autumn. 
 The following curve made by Wickman demonstrates very clearly 
 the great increase in the number of cases which occurred during 
 the months of July to October, 1905, in Sweden (fig. 50). 
 
 The highest point of an epidemic may be somewhat delayed. 
 This happened with our own cases in Hesse-Xassau which were 
 observed by Ed. Muller; he found many more cases during October 
 and November than in August and September (fig. 51). The com- 
 parative distribution of the cases in the Swedish epidemic observed 
 by Wickman and of those of our own epidemic in Hesse-Xassau has 
 been put into tabular form by Ed. Muller (figs. 52 and 53). 
 
 Muller is probably correct in surmising that the delay in reach- 
 ing its highest point which was seen in our epidemic was due to 
 the fact that the contagion passed over to us from Westphalia rather 
 late in the year. 
 
 Wickman mentions that the maximum in an epidemic may be 
 reached during the winter months. Such an epidemic was recorded 
 in the north of Sweden. The onset of winter does not guarantee 
 that an epidemic will cease in some cases. Here I may mention 
 again the extraordinary resistance to cold shown by the virus. The 
 Australian epidemics are no exception to the rule that the disease 
 occurs during the summer months, because March and April in 
 Australia correspond to our summer. 
 
 Age, Sex, Predisposition.— Reports from the different 
 epidemics agree as regards the usual ages at which patients are 
 attacked by the disease. Children are most affected, although the 
 epidemics show very clearly that adults are attacked more often 
 than was formerly supposed. The percentage rate of incidence of 
 
EPIDEMIOLOGY 
 
 143 
 
 the disease cannot be expressed more clearly than by the curves 
 constructed by Ed. Miiller (figs. 54-57)- 
 
 Ninety-six per cent, of all cases occur during the first decade 
 (fig. 54), and nine-tenths of these children had not readied the age 
 of five years (fig. 55). More than three-quarters of the cases 
 occurred" during the first three years of life, of these most in the 
 second year (fig. 56), and mainly in the second half of that year 
 
 
 Jan. 
 
 Feb. 
 
 Mar. 
 
 April 
 
 May 
 
 June 
 
 July 
 
 Aug. Sept. 
 
 Oct. 
 
 Nov. 
 
 Dec. 
 
 350 
 
 - ! 
 
 
 
 
 
 1 1 
 
 
 
 
 300 
 
 550 
 200 
 
 
 
 
 
 
 
 
 
 — 1 — 
 
 
 
 
 
 / ' > 
 
 
 150 
 
 100 
 
 to 
 
 - 
 
 
 
 • 
 
 
 
 
 
 
 1 
 
 ■k 
 
 
 Fig. 50. 
 
 Monthly number of cases of Heine-Medin 
 disease in Sweden (after Wickman). 
 
 50°/o 
 40% 
 30°/o 
 20% 
 lOO/o 
 0°/o 
 
 Aug. 
 
 Sept. Oct. 
 
 Nov. Dec 
 
 - 
 
 «V?a 
 
 1 
 
 " 
 
 
 \«?» 
 
 / \ 
 
 / 
 
 \ 
 
 ~6% 
 
 --"WMl 
 
 k 
 
 FIG. 
 
 Percentage of fre- 
 quency of cases in 
 Hesse - Nassau from 
 August to December, 
 1 909 (after Ed. 
 
 Miiller). 
 
 Fig. 52. 
 
 Distribution of Wickman ; s cases 
 in the third and fourth quarters 
 (Swedish epidemic, 1905). (After 
 Ed. Miiller.) 
 
 50° 
 60% 
 
 III Q. IV. Q 
 
 : «•. 
 
 - / 
 
 
 - / 
 
 60% 
 40% 
 S0% 
 20% 
 IOO/ 
 0% 
 
 - / 
 
 - J 
 
 - \ 
 
 - \ 
 
 - 1SV 
 
 
 - 
 
 
 Fig. 53- 
 
 Distribution of cases in Hesse- 
 Nassau in the third and fourth 
 quarters. (After Ed. Miiller.) 
 
 (fig. 57). The experience of other investigators at other places 
 coincides with this. 
 
 Males are somewhat more affected than females, but the differ- 
 ence is not large. Most observers have been unable to detect any 
 
144 
 
 EPIDEMIC INFANTILE PARALYSIS 
 
 indications that predisposition plays any role in the disease. Strong 
 and healthy children are affected quite as often and as severely as 
 weakly children; in particular, children with a neuropathic taint 
 show no special liability to the disease. 
 
 While discussing the pathogenesis of the disease I have already 
 touched on the question : Why children are so easily and frequently 
 attacked. 
 
 100% 
 80% 
 80% 
 70% 
 60% 
 SOO/o 
 40% 
 30% 
 20% 
 lOO/o 
 0% 
 
 -1 D. -2D. -3D. 
 
 |Z'» Z 
 
 »0% 
 
 80% 
 70% 
 «0% 
 60% 
 
 (0"„ 
 •0% 
 
 ao% 
 
 lOO/o 
 
 -iY. 
 
 -ioY 
 
 -isY 
 
 -20Y" 
 
 -25Y 
 
 -30Y. 
 
 |«% 
 
 
 
 
 
 " 
 
 
 
 
 
 
 " 
 
 
 
 
 
 
 
 
 
 
 
 
 
 , 
 
 
 
 
 
 
 
 
 
 
 
 - 
 
 
 
 
 
 
 - 
 
 
 
 
 
 
 
 ^U 
 
 7% 
 
 2% 
 
 ^0% 
 
 Fig. 54- 
 
 Percentage distribution of the 
 cases among the first three decades 
 of life. (After Ed. Muller.) 
 
 FIG. 55- 
 
 Percentage distribution of cases 
 in the first six 5-yearly periods of 
 life. (After Ed. Muller.) 
 
 -lY. -2Y. -3Y. -4Y. -5Y. -6Y. -?Y. -8Y. -9Y. -10Y. 
 
 - 
 
 A3 
 
 ?°o 
 
 
 
 
 
 
 
 
 - / 
 
 
 \20 
 
 
 
 
 
 
 
 
 _«% 
 
 
 
 
 
 
 
 
 
 
 - 
 
 
 
 Vr 
 
 ^ 
 
 vs. 
 
 J°o 
 
 ~~!2£. 
 
 0'. 
 
 iv. 
 
 Fig. 56. 
 
 Percentage distribution of cases in 
 the first ten years of life. (After Ed. 
 Muller.) 
 
 60% 
 50% 
 40O/ o 
 30% 
 20% 
 10 0/0 
 0% 
 
 •IM. -12 M -18 M. -24 M. 
 
 - 
 
 
 
 50% 
 
 - 
 
 
 
 
 - 
 
 
 
 
 - 
 
 21,1- 
 
 ' / 
 
 
 - / 
 
 
 ^•ttl 
 
 Z'/. 
 
 _ >a < 
 
 % 
 
 
 
 FIG. 57- 
 
 Percentage distribution of 
 cases in the first four half years 
 of life. (After Ed. Muller.) 
 
 Proof Of Contagiousness. — Now that a living micro-organism 
 is known to be the cause of Heine-Medin disease, the question arises 
 as to how infection takes place and what are the sources of 
 contagion. 
 
 The first observations to be mentioned are those which relate 
 to the occurrence of paralysis in certain animals, chiefly in dogs, 
 fowls and rabbits, at the same time as epidemics of infantile 
 paralysis in human beings. Such a coincidence is very hypothetical, 
 and is rendered still more unlikely by the number of epidemics 
 
EPIDEMIOLOGY 145 
 
 which have been observed which were not associated with any such 
 disease in animals. The evidence obtained from experimental work 
 all points in the opposite direction, all these kinds of animals being 
 proved to be not susceptible to the cause of Heine-Medin disease in 
 man. It would be of scientific interest to determine in what relation 
 the active agent of Borna's disease in horses stands towards the 
 virus of poliomyelitis in man, because of the extraordinary 
 similarity, not to say identity, of the microscopical lesions in the 
 two cases. 
 
 Since it is exceedingly doubtful whether the disease may 
 be transmitted from an animal to man, it becomes necessary to 
 determine whether infantile paralysis can pass from man to man 
 and so belong to the contagious variety of diseases. In this con- 
 nection the older observations offer a certain amount of evidence, 
 e.g., Cordier's statement that he saw the disease in one patient who 
 had previously visited another. The occurrence of several cases 
 in one family pointed in the same direction; further, Leegaard 
 observed that an epidemic followed the lines of traffic. 
 
 All these examples were only significant, and until 1905 there 
 was no clear proof of the contagiousness of the disease; up to that 
 time observers were inclined to take rather the opposite view, e.g., 
 Medin thought that direct infection was exceedingly rare, and 
 Zappert was definitely opposed to the idea. 
 
 The exemplary investigation into the Swedish Epidemic of 1905 
 by Wick-man turned the current of opinion in a contrary direction. 
 
 Wickman worked under particularly favourable conditions; 
 owing to compulsory notification being enforced by the Govern- 
 ment he was able to investigate every single case. Further, the 
 lonely parishes of Sweden with their isolated farms and houses made 
 it possible to trace the course of the epidemic under very simple 
 conditions. Wickman did not shirk the labour of tracing every 
 case, and he made it possible to obtain a clear general view of the 
 individual cases by the use of maps. Xo one, who wishes to 
 gain a thorough knowledge of the epidemiology of the disease, can 
 avoid the trouble of carefully examining the studies of Wickman. 
 
 We shall only summarize Wickman's arguments, by which he 
 proved that Heine-Medin disease is contagious, i.e., communicable 
 from man to man. 
 
 In the first place, in the Swedish epidemic it was possible to 
 prove contact between the individual cases almost universally. It 
 is true that contact was not direct in every case, frequently there 
 were intermediaries who remained healthy. Wickman would never 
 have been able to establish this fact if he had not known of the 
 abortive cases from his clinical studies and had not taken them into 
 consideration. When this is not done it happens too often, as I 
 mentioned in the first chapter, that the hasty and incorrect conclu- 
 sion is reached that no contact has occurred between the cases. 
 Wickman made a careful analysis of the circumstances accom- 
 panying infection in almost every case, 1,031 in all. 
 
 10 
 
I46 EPIDEMIC INFANTILE PARALYSIS 
 
 His observations in the little parish of Traestena have become specially 
 celebrated, because they form a classical example of his theory that the 
 disease is contagious. Out of 500 inhabitants, living in 102 houses, mostly 
 isolated from one another, 49 persons (= 10 per cent.) became ill, 26 of 
 these (= 5 per cent.) had de'finite paralysis. The source of infection in most 
 cases was the school ; the disease was carried to the different houses by the 
 children, some of whom became ill themselves, while others remained well. 
 Wickman therefore arrived at the important conclusion that the disease 
 could spread by means of " carriers," as in the case of so many other infec- 
 tious diseases. Where it was not possible to trace the infection directly to 
 the school, it could be proved that visits had taken place to houses which 
 had already been infected from the school. The infection spread from this 
 parish in a radial manner, in the same way as was observed in larger 
 affected areas. 
 
 Even when it was not possible to trace the spread of the 
 epidemic so clearly as in the above example, yet the grouping of 
 the cases was important; in many instances several persons in one 
 house or in adjacent houses were attacked. Further, the connec- 
 tion between the chief roads and railways and the spread of the 
 disease was very evident, particularly among the more scattered 
 cases. 
 
 From all these facts Wickman came to the conclusion that 
 Heine-Medin disease behaves exactly like other contagious diseases 
 as far as its method of spread is concerned. Wickman explained 
 also why this had not been recognized before. The earlier small 
 epidemics had not given opportunities for such observations, and 
 the importance of abortive cases and of healthy carriers had not 
 been recognized. 
 
 Wickman considers that indirect transmission, i.e., by non- 
 living objects, is a great rarity. He himself only met with one 
 case in which the infection was carried by a picture, and one in 
 which the milk was blamed. These observations have remained 
 unique; no similar examples of indirect transmission have been 
 reported. 
 
 Confirmation of Wickman's Statements. — Subsequent epi 
 -demies provided excellent opportunities of testing Wickman's 
 conclusions. In our epidemic in Hesse, Mullef succeeded in 
 tracing very clearly the track of the epidemic, because the number 
 of cases was not very great, and in many villages only one case 
 occurred. A tendency to grouping of the cases was observed. 
 As in Sweden, it was abundantly clear that the infection followed 
 the lines of the railways and the great roads. Miiller was able to 
 find cases in which the infection was brought by healthy carriers 
 and could have been brought in no other way. 
 
 A particularly instructive example was provided in the case of the small 
 epidemic in the little town of Frankenau. The midwife of the town had 
 visitors from Westphalia from September 11 to the 13th. On the 20th one 
 of her children was stricken with paralysis and two others suffered from 
 gastro-intestinal symptoms. Some time later a neighbour's child, who had 
 
EPIDEMIOLOGY 147 
 
 played with the children of the midwife who had remained unaffected, 
 became ill, so also a child of the schoolmaster (the healthy children of the 
 midwife attended the school); finally, the child of a workman became ill, 
 who had been in the same schoolroom with the midwife's children. The 
 track of the epidemic was therefore as follows : The virus was brought by 
 healthy carriers from Westphalia; in the village it was disseminated by the 
 healthy children of the midwife. 
 
 Direct transmission of the disease by the patient was more rare, 
 a fact which had been observed by Wickman. Muller found the 
 disease less among" the peasants who remained on their land than 
 among those who followed a trade, particularly those that came 
 much into contact with the rest of the world (inn-keepers, coach- 
 men, postmen, and railway workers); shoemakers or their children 
 were curiously often affected, a fact noticed also by Eichelberg. 
 
 Confirmation of Wickman' s observations, particularly of those 
 with reference to the subject of the healthy carrier, was given by 
 the reports of Krause (Westphalia), Leegaard (Norway), Xetter 
 (France), of Locker, Lindner and Mally (Upper Austria), and also 
 of Emerson, Armstrong, Jones, Shidler, and, to a certain extent, 
 Lovett, who all reported American epidemics. 
 
 Zappert is very reserved in his opinion on the contagiousness 
 of the disease. He observed grouping" of the cases in Lower 
 Austria; in Vienna itself the disease appeared in certain quarters of 
 the city and in certain groups of houses; occasionally he saw more 
 than one case in the same family; but he was quite unable to trace 
 any connection between the different cases. It must be remembered 
 that he had to carry out his research in a large capital and in a thickly 
 populated province. 
 
 No proofs of the contagiousness of the disease could be obtained 
 in the great epidemic in New York in 1907, nor in the epidemic in 
 the Steiermark (Furntratt, Potpeschnigg) nor in Pomerania 
 (Peiper). Wickman quite rightly emphasizes the fact that all these 
 ■observers were unable to prove any other method of transmission 
 ■of the disease. 
 
 The reasons usually brought forward against the theory of 
 •contagion are the occurrence of completely isolated cases, the 
 observation that so often only one child in a family is affected, 
 the absence of any epidemics in hospitals, and the occasional 
 appearance of the disease among the "most isolated" people 
 (prisoners!). It is, however, questionable whether these isolated 
 people are really so isolated as they appear to be; in particular it 
 must be remembered that abortive cases may have occurred in the 
 neighbourhood and that contact with healthy carriers is possible. 
 Serum diagnosis may throw some light on these cases (see following 
 ■chapter). 
 
 Wickman justly draws the comparison between Heine-Medin 
 ■disease and cerebrospinal meningitis; the epidemiology of the two 
 diseases has many points in common; in both, children are chiefly 
 affected, adults are not entirely immune, only one or, at most, two 
 
I48 EPIDEMIC INFANTILE PARALYSIS 
 
 children in a family are affected, the disease is certainly transmitted 
 by healthy carriers, " sporadic " cases occur, and finally, no com- 
 pletely satisfactory explanation of the epidemic occurrence of the 
 diseases has ever been found. Scarlet fever might be instanced for 
 comparison on many points. 
 
 No sound argument has been brought against the contagion 
 theory so far. 
 
 All attempts to find another way by which the infection travels 
 have failed, such as transmission by drinking-water (epidemics in 
 towns with a faultless water supply), by fruit (epidemics at a time 
 when there was no fruit), by cow's milk (children at the breast have 
 contracted the disease, see Wickman's exception quoted above), 
 and by other articles of food. Transmission by insects is not pro- 
 bable because of the occasional epidemics during the winter. 
 
 Certain observations seem to support the idea that the virus 
 may remain in a house (i.e., on non-living things) and thus be 
 transmitted. That the virus has been proved experimentally to 
 remain active for a long time is an argument in favour of this view, 
 which deserves consideration. 
 
 We agree with Wickman that the chief method of transmission 
 of the disease is the direct one, from human being to human being. 
 
 It is very difficult to say how infection takes place. When 
 discussing the pathogenesis of the disease we arrived at the con- 
 clusion that probably the lymphatic tissues of the mouth, nose, 
 throat, and alimentary tract, served as the portal of entry of the 
 virus. Many things point to the virus remaining for a long time 
 in the mucous membrane of the mouth and throat of infected 
 individuals. One might think of infection by the saliva in speaking, 
 coughing, sneezing, or in more direct contact. Unfortunately 
 there is as yet no proof that the virus is contained in the saliva. 
 I have given monkeys an intracerebral injection of saliva filtered 
 through a Berkefeld filter from cases of poliomyelitis and have not 
 succeeded in producing the disease. Considering how little we 
 really know about the pathogenesis of the disease, any attempt to 
 explain how infection occurs under the conditions of an epidemic 
 must be fraught with almost insuperable difficulties. 
 
 One fact may be accepted as practically proved by Wickman — 
 the disease is contagious. Xo one knows how infection takes 
 place, whether by direct contact, by the breath, by virus which has 
 adhered to non-living objects, clothes and shoes, or finally, by 
 some animal carrier which has been overlooked. We are still at 
 the beginning of this question. 
 
 There are tzi'o mysteries awaiting an explanation. The one is- 
 general in character, the question hozu the great epidemics arise. 
 The other is particular, how does infection fake place in each 
 epidemic ? 
 
 [Kling, Wernstedt, and Pettersson bave since succeeded in 
 producing the disease in monkeys by using saliva and intestinal 
 contents. Neustaedter and Thro succeeded in using dust from the 
 sick-room for this purpose. — Translator.] 
 
CHAPTER VI. 
 
 The Fight Against the Disease. 
 
 I.— IMMUNITY AND IMMUNIZATION. 
 
 Clinical and Epidemiological Experience.— Before attempting 
 to produce artificial immunity to an infectious disease, it is necessary 
 to consider whether the evidence points to the development of a 
 natural immunity in the course of the disease. In the case of 
 Heine-Medin disease this inquiry leads to no definite conclusion and 
 is beset with difficulties. In the first place, we have only recently 
 become acquainted with the epidemic form of the disease ; secondly, 
 the total number of cases is, fortunately, relatively small, and they 
 occur within narrow limits of ag'e. Even though many children 
 survive one epidemic, by the time that another occurs these patients 
 have attained an age in which infection is rarely found. It is con- 
 sequently very difficult to prove by figures that one attack of Heine- 
 Medin disease protects against a second attack. 
 
 However, it is worth placing' on record that observers who 
 have paid special attention to this point and who have had the 
 opportunity of observing large epidemics, have never seen the 
 disease attack the same child twice (Wickman, Ed. Miiller, Stiefler). 
 Harbitz and Scheel observed the great Norwegian epidemic, and 
 state that " it seems proved beyond doubt that when a district has 
 been visited by the disease in one year, it remains free during the 
 following years." Zappert came to the same conclusion in the 
 course of his extensive studies. In 1898 there was an epidemic in 
 Vienna, and in the following year the number of cases was much 
 below the average; this corresponds also with our experience with 
 regard to other infectious diseases : the number of cases in the years 
 following an epidemic is always remarkably small. 
 
 There are a few records which indicate that the same individual 
 may suffer twice from the disease. Eshner saw a patient who had 
 the first attack at the age of three and the second at fourteen. The 
 exact nature of the second illness is, however, not quite clear; it is 
 not impossible, though improbable, that it was really a traumatic 
 neuritis. Eckert reported another case, unfortunately giving very 
 meagre details: " H. Sch. was attacked by poliomyelitis in 
 
150 EPIDEMIC INFANTILE PARALYSIS 
 
 September, 1903. Tenotomy and a mechanical support were neces- 
 sary for the left leg - , which was paralysed. At the beginning of April, 
 1909, he suffered from a second attack, in which the right leg was 
 paralysed." Unfortunately I have been unable to see the original 
 paper by Sterne, quoted by Netter and Levaditi, in which a large 
 number of cases were reported in adults, who had suffered from 
 poliomyelitis during childhood. In these cases the second attack 
 followed 9. 17, 19, 23, and 54 years after the first. 
 
 It is quite possible that if immunity be established it does not 
 last throughout a lifetime; Sterne's results might be explained on 
 this assumption. Further, it must be remembered that increase 
 of paralysis does not always mean a second attack of the disease; 
 a spinal cord which has once been damaged is particularly liable 
 to further damage of a non-specific kind, with destruction of those 
 elements which had remained capable of functioning. But even 
 although isolated cases of reinfection do occur, that does not do 
 away with the possibility that survival of one attack leaves behind 
 it a specific protection against another. Even in the case of 
 diseases, such as small-pox, in which this occurs to a very marked 
 degree, occasional exceptions to the law of immunity are met with. 
 Biological laws are not mathematical in their application. 
 
 Relapses, which are very rare, constitute no proof that 
 immunity is not conferred by an attack of the disease. Medin and 
 Neurath both observed relapses. Wickman found them exceedingly 
 rarely, and Ed. Miiller not at all. I once saw a relapse in a case 
 of experimental poliomyelitis (see p. 59). Under these circum- 
 stances they appear to be extremely rare, and I believe that the two 
 cases described by Levaditi and myself are the only instances 
 known. 
 
 All these observations fail to prove that immunity is not con- 
 ferred, and yet it is very difficult to obtain exact proof of the 
 opposite, if one ignores the general impression obtained from the 
 study of epidemics. In the case of monkeys, which behave towards 
 the virus in other respects just like human beings, it is quite certain 
 that immunity is present. This makes it probable that in man one 
 attack produces immunity for a longer or shorter period against a 
 second attack. 
 
 The existence of such immunity may explain some of the 
 observations made during epidemics. Wickman was struck by the 
 small incidence rate of the disease. In the district which was 
 most severely affected only 5 per cent, of the inhabitants became 
 paralysed; the inclusion of all abortive cases only brought the 
 figure up to 10 per cent. Now, Wickman's observations offer 
 convincing proof that the virus may be transmitted by healthy 
 carriers; we know also, from our experience with typhoid fever, 
 cholera, and other diseases, that these clinically healthy carriers 
 have suffered from the infection in some way or another, because 
 specific products of reaction to the virus can be found in their 
 blood-serum. It seems to me worth considering whether we shall 
 
THE FIGHT AGAINST THE DISEASE 151 
 
 not eventually find specific antibodies in the serum of a large 
 number of apparently healthy people during an epidemic. Such a 
 discovery would be of the greatest importance epidemiologically 
 and, merely as a working hypothesis, such a consideration will be 
 of value to future investigators. 
 
 Attempts to Reinfect Monkeys. — Apart from all epidemi 
 ological considerations it would have been natural to make investi- 
 gations into the question of immunity in experimental poliomyelitis. 
 The existence of a successful method of protective inoculation in 
 the case of the analogous disease of rabies, although the epidemi- 
 ology of that disease offered no evidence of the occurrence of 
 immunity, would in itself have stimulated us to make the experi- 
 ment. The following is a series of experiments in which monkeys 
 which had survived the first infection were given a second injection 
 of the virus. 
 
 Experiment 1. — On December 28, igog, the following monkeys received 
 an intracerebral injection of '5 c.c. of an emulsion of virus No. 11. 
 
 (a) Control monkey No. 16 {Macacus rliesus). 
 
 December 2Q-January 2. — Well. 
 
 January 3. — In the evening rather tired, looks cross. 
 
 January 4. — Severe flaccid palsy of both arms and the neck; slight 
 weakness in the hind limbs. 
 
 January 5. — Lies on the floor, apparently completely paralysed. Death 
 at noon. Microscopical appearances typical. 
 
 (b) Monkey No. 6 (Macacus rhesus) received an intracerebral injection of 
 '8 c.c. of virus of Case 3, passed through Berkefeld filter, on December 2 
 and 4. Remained perfectly well. Interval between the two infections 
 twenty-four to twenty-six days. 
 
 Course of the infection on December 28 : — 
 
 December 29-January 7. — No symptoms. 
 
 January 8. — Spares the right hind limb. 
 
 January 9. — Paresis of right hind limb more noticeable. 
 
 January 10. — Paresis scarcely to be seen. 
 
 January 11. — Still slight paresis. 
 
 January 12 et seq. — Well. The monkey lived until June 15, 1910; 
 occasionally a trace of weakness was noticed in the right hind limb. 
 
 Experiment 2. — The following monkeys received an intracerebral 
 injection of "5 c.c. of virus No. 12 on January 3, 1910 : — 
 
 (a) Control monkey No. 17 (Macacus rhesus). 
 January 4-15. — Well. 
 
 January 16. — Sad and cross. 
 
 January 17. — Flaccid paralysis of both hind limbs. 
 
 January 18. — Lies on the floor of the cage with all limbs apparently 
 paralysed. Death in the evening. 
 
 Microscopical appearances typical. 
 
 (b) Monkey No. 8 (Cerco-pithecus ruber) received '4 c.c. of virus No. 3 
 (intracerebral injection) on December 4, 1909; afterwards suffered from the 
 abortive type of the disease (see p. 38). 
 
 Interval between the injections, thirty days. 
 
 Result of injection January 3. — Remained quite well. 
 
152 EPIDEMIC INFANTILE PARALYSIS 
 
 Experiment 3. — The following monkeys received an intracerebral 
 injection of an emulsion of virus Xo. 11 on January 6, 1910 : — 
 
 (a) Control monkey (Mangabey) received '2 c.c. January 7-17. Xo 
 symptoms. 
 
 January iS. — In the afternoon, definite flaccid paresis of both hind limbs. 
 
 January 19. — Paresis more marked. Slight paresis of the arms. 
 
 January 20. — Total flaccid paralysis of both hind limbs: definite slight 
 paresis of the arms. 
 
 January 21-23. — Gradual increase of paralysis. 
 
 January 24. — Total paralysis of all limbs. Death in the afternoon. 
 Microscopical appearances typical and extensive. 
 
 (b) Monkey No. 9 (Mangabey) received a subcutaneous injection of 1 c.c. 
 of an emulsion of the virus of Case 3 on December 4, 1909. and remained 
 well. 
 
 Interval between the two inoculations thirty-three days. 
 Result of re-infection ('2 c.c. intracerebral). — Remained permanently 
 well. 
 
 (c) Monkev Xo. 10 (Mafigabey) received an intraneural injection of "2 
 c.c. of the virus from Case 3 on December 4, 1909, and remained well. 
 
 Interval between the inoculations, thirty-three days. 
 
 Result of reinfection ('5 c.c. intracerebral, i.e., two and a half times 
 the dose given to the control) : — 
 
 January 16-19. — Trace of paresis of left fore limb. 
 
 Januarv 20 et seq. — Quite well. General condition remained normal 
 throughout. 
 
 Experiment 4. — The following monkeys received intracerebral injections 
 of '35 c.c. of virus Xo. 12 on February 7, 1910. 
 
 (a) Control monkey No. 29 (Macacus rhesus). 
 February S-14. — Well. 
 
 February 15. — Paralysed. 
 
 February 22. — Death. (For details, see p. 47.) 
 
 (b) Monkey Xo. 9 [Mangabey). For previous inoculation see Experi- 
 ment 3. Period between the second and third infection on February 7 was 
 thirty-two days. Result of last infection — Remained permanently well. 
 
 (c) Monkey Xo. 10 (Mangabey). For previous infection, see Experi- 
 ment 3. Period between that infection and the one on February 7 was 
 thirty-two days. Result — remained well. 
 
 (d) Monkey Xo. 6 (Macacus rhesus). For previous infection see Experi- 
 ment 1. Interval between inoculations, forty-one days. Result of last 
 infection — Remained well. 
 
 Experiment 5. — The following monkeys received an intracerebral injec- 
 tion of '6 c.c. of virus Xo. 11 on March 15, 1910 : — 
 
 (a) Control monkey Xo. 41 (Macacus cynomolgus). 
 March 16-25. — Remained well. 
 
 March 26. — Paresis of the legs. 
 
 March 27. — Paresis more marked. 
 
 April 1 et seq. — Gradual improvement (for details, .see p. 59).' 
 
 (b) Monkey Xo. 32 (Macacus rhesus) received an injection, causing a 
 paralysis which gradually improved, on February 7 \cf. p. 58). Interval 
 between first and second inoculation, thirty-six days. 
 
 Result of infection on March 15. — Remained permanently well. 
 
THE FIGHT AGAINST THE DISEASE 1 53 
 
 Experiment 6. — The following monkeys received an intracerebral injec- 
 tion of '6 c.c. of virus Xo. n on July 13, 1910 : — 
 
 (a) Control monkey Xo. 102 (Macacus rhesus). 
 July 14-24. — Well. 
 
 July 25. — Flaccid paresis of hind limbs and weakness of the trunk. 
 In the evening paralysis of the hind limbs and of the left fore limb ; 
 right-sided facial palsy. 
 
 July 26. — Found dead. Microscopical appearances typical. 
 
 (b) Monkey No. 59 (Macacus rhesus) received an injection on June 13, 
 1910, which caused paralysis which improved. Interval between the infec- 
 tions, thirty days. 
 
 Result of reinfection. — Remained permanently well. 
 
 In six different series of experiments nine reinfected monkeys 
 proved to be immune to an infection which caused severe paralysis 
 in the control monkeys and, with one exception, caused death. 
 The interval between infection and reinfection varied from twenty- 
 four to forty-one days in my experiments. 
 
 The work of other experimenters provides further proof that 
 a monkey that has survived infection with poliomyelitis is immune. 
 Landsteiner and Levaditi reported the following- experiment on 
 January 3, 1910 : — 
 
 Three monkeys (Macacus rhesus, and Macacus cynomolgus), of which 
 two had been paralysed for twelve days and the third for twenty-five days, 
 together with a control monkey (Macacus cyuouwlgus), were reinfected. 
 The control became paralysed in five days, and died on the sixth day. The 
 three reinfected monkeys remained well. 
 
 The experiment shows that immunity is present twenty-one 
 days after the first infection and twelve days after the appearance 
 of paralysis. 
 
 Flexner and Lewis were the first to report a reinfection experi- 
 ment on January 1, 1910: — 
 
 Monkey 45, paralysed as a result of an intracerebral infection on 
 November 6, 1909, was reinfected, together with two control monkeys, on 
 November 30, igog. The latter became typically paralysed, the reinfected 
 monkey remained well. 
 
 In their summary of later date Flexner and Lewis report that 
 they had found monkeys to be immune from eight days to two 
 months after the onset of paralysis. 
 
 The experience of Leiner and v. Wiesner was similar. They 
 published no less than twelve separate experiments with a positive 
 result; reinfection was performed 2, 7, 9, 25, 31, 41, 52, 55, 60, 66, 
 87 and 99 days after the occurrence of paralysis. They have per- 
 formed the service of showing that immunity is present as early as 
 two days and at least as late as ninety-nine days after the appear- 
 ance of paralysis. 
 
 The summation of all these similar results leaves no doubt that 
 the survival of an attack of poliomyelitis which is accompanied by 
 paralysis confers immunity upon monkeys. The condition laid 
 
154 EPIDEMIC INFANTILE PARALYSIS 
 
 down by Krause and Meinicke is not necessary, viz., that long- 
 series of experiments in more suitable animals are required before 
 the fact of immunity can be conclusively proved. There is also no 
 doubt that Krause and Meinicke are wrong in believing that increase 
 in the age of the monkeys can be the cause of the immunity in the 
 experiments detailed above. 
 
 Immunity after an attack which has caused paralysis seems to 
 be the rule in monkeys. The only experiment with an opposite 
 result is one quoted by Leiner and v. Wiesner : Monkey No. 172, 
 infected on February 11. 1910, was paralysed on February 23. 
 It was reinfected on March 12, and became ill and more paralysed 
 on March 30. (The control became paralysed on March 17.) In 
 this case the shortness of the incubation period in the control 
 renders it probable that the infection was very severe, and this 
 single case does not disprove the rule of immunity. After all, every 
 immunity is relative. 
 
 It is more difficult to determine whether an infection which 
 does not cause paralysis confers immunity. I have the impression 
 that an unsuccessful inoculation increases the resistance of the 
 animal (cf. Experiment 3 above); but I have no doubt that the 
 immunity thus conferred is neither so certain nor so powerful as 
 that which follows definite paralysis. The following experiments 
 show that reinfection may be successful when the first infection has 
 had no result : — ■ 
 
 Experiment 7. — The following monkeys, on December 14, IQ09, received 
 an intraperitoneal injection (3 c.c.) and an intracerebral injection ('5 c.c.) 
 of a 20 per cent, emulsion of virus Xo. 11. 
 
 (a) Control monkey No. 13 (Macacus rhesus). 
 December 15-25. — Well. 
 
 December 26. — Paresis of the hind limbs. 
 
 December 27. — Marked paralysis of the hind limbs, commencing para- 
 lysis of the fore limbs. 
 
 December 28-January 2, 1910. — Slight improvement. 
 
 January 3. — Paralysis more marked. 
 
 January 4. — Total paralysis. 
 
 January 5. — Found dead. Microscopical appearances typical. 
 
 (b) Monkey No. 4 (Macacus rhesus) received, on November 27, 190Q, 
 an intracerebral injection of an emulsion of virus from Case 2 (see p. 37), 
 and suffered subsequently from a doubtful ( ? abortive) poliomyelitis from 
 the fifth to the seventh day after the infection. Interval between the infec- 
 tions, seventeen days. 
 
 Result of reinfection on December 14. — 
 December 15-22. — No symptoms. 
 December 23. — Definite paresis of all limbs. 
 December 24. — Total paralysis of all limbs; death. 
 Microscopical appearances typical. 
 
 Experiment 8.— -The following monkeys were given an intracerebral 
 injection of '5 c.c. of virus No. 6 on December 17, 1900. 
 (a) Control monkey No. 14 (Macacus rhesus). 
 
THE FIGHT AGAINST THE DISEASE 155 
 
 December 18-25. — Well. 
 
 December 26. — Paralysed. 
 
 December 30. — Death (for details, see p. 48). 
 
 (b) Monkey No. 5 {Macacus rhesus) was given an intracerebral injection 
 of virus No. 6 on December 1, 1909, and remained well. Interval between 
 the two infections, sixteen days. 
 
 Results of the reinfection :— - 
 
 December 18-23. — No symptoms. 
 
 December 24. — Paresis of the right hind limb. 
 
 December 25. — Paralysis of all limbs. 
 
 December 28. — Death. 
 
 I believed at first that the shortness of the interval between 
 the two injections would explain the successful reinfection of 
 monkeys Nos. 4 and 5. Xow, however, that it has been proved 
 that immunity, if present at all, is fully developed by the time at 
 which I reinfected the monkeys, I believe that after unsuccessful 
 inoculation immunity is established only in an irregular and feeble 
 manner; Leiner and v. Wiesner, Landsteiner and Levaditi, Flexner 
 and Lewis, have also found that monkeys which had been unsuc- 
 cessfully inoculated could be reinfected successfully. At the same 
 time I believe that immunity does follow unsuccessful intracerebral 
 injection in some cases and under certain conditions. It is possible 
 that the amount of virus used has some bearing" on this matter. As 
 far as I can see, most experimenters have used emulsion of spinal 
 cord, filtered through paper or centrifugalized for a short time; 
 on the other hand, I myself have used the virus unfiltered or have 
 merely allowed the coarser particles to settle. Flexner and Lewis 
 have shown in their later work that unsuccessful inoculation confers 
 immunity if large doses of virus have been used. They believe, 
 further, that injection of fresh virus into the brain, if not followed 
 by paralysis, does not produce immunity, but that virus preserved 
 in glycerine does do so. As their experience became more exten- 
 sive, Flexner and Lewis appear to have come to believe that 
 immunity does follow unsuccessful inoculation, but not with the 
 same certainty as after successful infection. 
 
 For practical purposes it does not much matter whether 
 unsuccessful intracerebral inoculation is followed by immunity; 
 such a method of immunization is not practicable. But it is of 
 importance to know whether immunity can be produced without 
 causing the disease. It was from this practical point of view that 
 I called attention to the existence of immunity in some of my cases 
 of unsuccessful inoculation. It will be only if no serious symptoms 
 are caused by the proceeding - that any method of preventive 
 inoculation can be of any practical use. Subsequent events have 
 given support to the optimistic view, which I adopted on perhaps 
 somewhat slender grounds. Authors, who at first denied the 
 possibility of such a thing, have published methods of immunization 
 which confer specific protection without causing an attack of the 
 disease. 
 
156 EPIDEMIC INFANTILE PARALYSIS 
 
 I have already touched on the question of the duration of the 
 immunity. Landsteiner and Leyaditi showed that it was still present 
 after twenty-five days, I myself after forty-one days, Leiner and 
 v. Wiesner after about 100 days, and Flexner and Lewis found it 
 four to five months after the onset of paralysis. 
 
 Methods of Immunization in Monkeys.— The attempt to dis- 
 cover a method of immunizing- monkeys which might be used in 
 human beings is not at present of great practical importance. 
 Only a small number of the children exposed to infection are 
 affected by the disease even in times of epidemic, and parents are 
 not likely to agree to preventive inoculation while the risks are 
 so small. On the other hand, it is possible that future epidemics 
 will be much more violent than they were in Scandinavia; the 
 character of the epidemics has changed very much even in the last 
 ten years. If we consider what a panic the disease causes during an 
 epidemic, and, further, how powerless we are when faced by the 
 disease in its acute stages, it must be evident that it is not only 
 justifiable, but it is the duty of experimental science to carry out 
 such investigations. 
 
 Many authors have endeavoured to find the most effective and 
 least dangerous method of artificial immunization of monkeys. 
 The experiments are still in the initial stages, but they provide a 
 very definite basis for further work on the same lines. 
 
 (a) Protective inoculation with dry virus. Pasteur's method 
 in rabies depends on the introduction of virus which has been dried 
 for different lengths of time. The analogy between the two 
 diseases led Landsteiner and Levaditi to attempt to produce 
 immunity by similar means. They proceeded exactly according to 
 Pasteur's method; the spinal cord of a monkey with poliomyelitis 
 was dried over caustic potash at a temperature of 22 C. for various 
 periods, and then rubbed up in physiological saline and injected 
 subcutaneously into the monkeys. 
 
 Monkeys Nos. 36 and 37 were treated in this manner. From December 3 
 to December 10, 1909, they received a daily injection of 2 c.c. of the 
 emulsion made from the dried spinal cord in the following way : — 
 
 December 3, cord dried for 9 days. 
 
 4 ,, „ „ 9 ,, 
 
 5 „ „ „ 6 „ 
 
 6 ,, „ ,, 6 ,, 
 
 7 „ ,, ,, 5 >> 
 
 8 „ „ „ 5 „ 
 
 9 „ „ ., 4 „ 
 10 „ ,, „ 3 ., 
 
 Ten days after the last vaccination monkey No. 37 was infected together 
 with a control monkey No. 51 (Cercofithecus). The control became para- 
 lysed after twelve days, and died three days later. Monkey No. 37 remained 
 well. 
 
 Monkey 36 was infected together with a control monkey No. sg 
 (Macacus cynomolgus) nineteen days after the last vaccination. The control 
 was paralysed in four days and died on the fifth. Monkey 36 remained well. 
 
THE FIGHT AGAINST THE DISEASE 1 57 
 
 As has been shown above, such a method does not diminish 
 the potency of the virus, and since Flexner and Lewis have proved 
 that subcutaneous injection may cause paralysis, such a method 
 should be rejected a priori. As a matter of fact, Landsteiner and 
 Levaditi found subsequently that subcutaneous injection of dried 
 virus does cause paralysis sometimes. 
 
 Example. — Monkey No. 87 {Macacus cynomolgus) received 
 on : — 
 
 January 27, 2 c.c. of virus dried for 21 days} ^. ,, „., , , ,• . c ., , • 
 
 ~J On the 5th, trembling ; 6th, paralysis ; 
 
 P ," ^ " >> 4 >) jtfi death with typical lesions. 
 
 February 4 ,, ,, 24 ,, ) ' ' }r 
 
 Monkey No. 86 {Macacus cynomolgus) received on: — 
 
 January 27, 2 c.c. of virus dried for 21 days\ 
 
 February 4 ',' ',', 24 " [ On February 11 paralysis and death. 
 
 9 ,'. ,', 25 „ J 
 
 The fact that the monkeys which were not paralysed by the 
 subcutaneous injection were mainly immune, proves that if sufficient 
 quantities of virus are used an unsuccessful inoculation may protect 
 against the disease. This confirms my own experience (see p. 155). 
 
 (/3) Immunization by small doses of virulent material. The 
 basis of Pasteur's treatment of rabies is the theory that the virus 
 becomes attenuated by being' dried. At the present time there are 
 g'ood reasons for believing' that drying" does not weaken the 
 individual particles of the virus, but that it does diminish their 
 number; it follows that in Pasteur's method of protective inocula- 
 tion the principle is really one of giving a small dose of fully active 
 virus at first and later giving larger and larger doses. In accord- 
 ance with this theory, Pasteur's method has been successfully 
 modified. It was natural that experiments should be made on these 
 lines in the case of poliomyelitis. Flexner and Lewis carried them 
 out. The following example may be quoted: — 
 
 A rhesus monkey received subcutaneous injections in the following 
 manner : — 
 
 January 12 to January 16, 1910 daily 35 c.c. virus of full virulence. 
 20 ,, 23 „ „ J 7 „ ,, 
 
 27 ,, 31 „ ,, -Ay ,, „ 
 
 The dose was gradually increased; the monkey received \ c.c, then 
 
 1 c.c, and on March 23, 1910, it received 5 c.c. virus of full virulence. 
 
 On April 2, 1910, this monkey received an intracerebral injection of 
 
 2 c.c. of virus of full virulence and remained permanently well. The virus 
 used in this case was exceedingly active and very constant in its action ; 
 a dose of even T i c c - C - killed a monkey which had not been previously treated, 
 after a normal, period of incubation. A high degree of immunity can be 
 attained by the use of the method of Flexner and Lewis; in the example 
 given above the animal was protected against 200 times the lethal dose. 
 
I58 EPIDEMIC INFANTILE PARALYSIS 
 
 Flexner and Lewis found later that one subcutaneous injection 
 of fully active virus conferred immunity. This was similar to my 
 own experience, as in experiment 3 (b) described above. The method 
 proved very inconstant in its action and dangerous, because many 
 of the animals became paralysed instead of only immunized. 
 
 (y) Immunization with virus attenuated or killed by chemical 
 means. Kraus was the first to make experiments in this direction. 
 By treating- the virus with '5 per cent, carbolic acid he believed that 
 he had obtained a safe and certain vaccine. He reported the 
 following experiment : — 
 
 On December 18, 1909, a monkey received a subcutaneous injection of 
 5 c.c. of fresh virus of full strength; on January 2, igio, it received a further 
 injection of 6 c.c. of post-mortem virus mixed with '5 per cent, carbolic acid. 
 A second monkey received, on January 3, 1910, 6 c.c. of virus mixed with 
 '5 per cent, carbolic acid. On January 13 these two monkeys and a control 
 monkey received an intracerebral injection of virus filtered through paper. 
 The control became paralysed on the twelfth day and died on the fourteenth. 
 Both the monkeys which had been treated previously remained well. 
 
 As a result of his experience with rabies, Kraus lays stress on 
 the use of virus filtered through paper in testing the immunity. It 
 is not clear in the above experiment whether the immunity of the 
 first monkey was due to the injection of the carbolized virus or of 
 the fully virulent virus. 
 
 Kraus recognized later, as did also Leiner and v. Wiesner, 
 Landsteiner and Levaditi, that even after five days '5 per cent, of 
 carbolic acid did not kill the virus in every case (see p. 67), and that 
 this method was therefore not without danger; consequently, in his 
 more recent experiments he always used virus which had been 
 rendered harmless by treatment with 1 to ii per cent, carbolic acid 
 for six days, and which had been freed from all coarse particles by 
 centrifugalization before it was so treated. One injection of virus 
 prepared in this way protected monkeys against subdural infection 
 carried out fourteen days to two months later with virus (filtered 
 through paper) which was fatal to the control monkeys. 
 
 I made one unsuccessful attempt to produce immunity by the 
 use of virus killed with formalin. 
 
 Monkey No. 35 (Macacus rhesus) was given an intracerebral 
 injection of virus treated with formalin on February 26 without 
 result. 
 
 On March 22 this monkey, together with a control monkey Xo. 43, was 
 infected with virus Xo. 12 (intracerebral, "6 c.c; intraperitoneal, 3 c.c). 
 Course of the infection : — 
 Monkey Xo. 35 : — 
 March 23-April 26. — Xo symptoms. 
 April 7. — Weak in the hind limbs. 
 
 April 8. — Definite flaccid paresis of both hind limbs and the left arm. 
 April 9. — Paresis more marked. 
 April 10-15. — Xo change. 
 
THE FIGHT AGAINST THE DISEASE 1 59 
 
 April 16.— Both arms markedly paretic; both hind limbs completely 
 paralysed. 
 
 April ig. — Died with increasing paralysis. 
 
 Microscopical appearances typical. 
 
 Monkey Xo. 43 : — 
 
 March 23-April 4. — Xo symptoms. 
 
 April 4. — Depressed ; does not want to climb. 
 
 April 5. — Marked paralysis of all limbs. 
 
 April 6.— Death. 
 
 Microscopical appearances typical. 
 
 (8) Immunization with heated virus. If any method of pro- 
 tective inoculation is ever used it will have to be one which can 
 be guaranteed to be harmless. The monkey is an animal which 
 shows unmistakably the lesions of poliomyelitis after intracerebral 
 inoculation. Although we did not succeed, we aimed at finding a 
 virus which would confer immunity and yet be harmless when 
 injected into the brain of monkeys. For this purpose we studied 
 virus which had been subjected to high temperatures. On page 65 
 we have already given some of our results. Intracerebral injection 
 of virus which had been heated for half an hour at ^ l = ) ° and at 50 
 proved harmless to monkeys: when heated at 45 the virus was 
 less active. Subcutaneous injection of virus heated to 45°, 50 , or 
 55 was quite harmless. Monkeys treated with virus prepared by 
 these methods were tested in many ways. 
 
 Experiment 1. — The following monkeys received intracerebral injec- 
 tions of '6 c.c. of virus Xo. 11 on March 15, igio : — 
 
 {a) Control monkey Xo. 41 (Macacus rhesus). Paralysed on the 26th. 
 Recovered. (Details on p. 59). 
 
 (b) Monkey Xo. 32 (Macacus rhesus), which suffered on Februarv 7, 
 1910, from paralysis caused by intracerebral injection of virus heated to 
 45 (see p. 65). After the infection on March 15 no symptoms observed for 
 two months. 
 
 (c) Monkey Xo. 34 [Macacus rhesus) received subcutaneous injections 
 of 2 c.c. of virus heated to 45 on February 7 and 9. 
 
 Result of the infection on March 15. — Xo paralysis; died of secondary 
 infection on the 22nd. 
 
 Xo lesions of poliomyelitis could be found. 
 
 Experiment 2. — The following monkeys received intracerebral injec- 
 tions of '6 c.c. of virus Xo. 11 on May 31, 1910. 
 
 (a) Control monkey Xo. 58 (Macacus rhesus). 
 May 31-June 10. — Xo symptoms. 
 
 June 11. — Paralysed. 
 
 June 13. — Death. Typical microscopical appearances. For details, see 
 P- 77)- 
 
 (b) Monkey Xo. 51 (Macacus rhesus) had had an intracerebral injection 
 of virus heated to 50 with no result on April 25, 1910 (cf. p. 65). 
 
 Result of the infection of May 31. — Remained permanentlv well. 
 
 (c) Monkey Xo. 52 (Macacus rhesus) received a subcutaneous injection 
 of virus heated to 50 on April 25, 1910, without result. 
 
 Result on infection on May 31. — Remained permanentlv well. 
 
l6o EPIDEMIC INFANTILE PARALYSIS 
 
 The other monkeys treated without result with virus heated to 50°, 
 monkey No. 53 (3 c.c. on April 25, 27 and 29, subcutaneously), and monkey 
 No. 54 (daily from April 25 to April 30, 3 c.c. subcutaneously), died of 
 pulmonary tuberculosis before their immunity could be tested. 
 
 Experiment 3. — The following monkeys received an intracerebral injec- 
 tion of '6 c.c. of virus No. 12 on March 2, igio : — ■ 
 
 (a) Control monkey No. 37 (Macacus rhesus). 
 March 9. — Totally paralysed. 
 
 Gradually recovered (see p. 57). 
 
 (b) Monkey No. 27 (Mangabey) received 5 c.c. of virus heated to 55 
 subcutaneously on January 25 and January 29 without any result. 
 
 Result of the infection on March 2, 1910 : — 
 
 March 11. — Depressed. 
 
 March 13. — Cerebral symptoms. 
 
 March 14. — Death from cerebral paralysis. (For details, see p. 53.) 
 
 [Two other monkeys inoculated with virus heated to 55 unfortunately 
 died of intercurrent disease before their immunity could be tested. Monkey 
 No. 28 received a subcutaneous injection of 5 c.c. on January 25 and January 
 29 with no effect; monkey No. 26 intracerebral injection of '5 c.c. on the 
 25th without result.] 
 
 These experiments, which must be confirmed, seem to show 
 that virus heated to 55 is quite harmless, but no longer has 
 sufficient immunizing power. Landsteiner and Levaditi had the 
 same experience. Monkeys treated by subcutaneous injection with 
 virus heated to 55 for half an hour succumbed to infection caused 
 nine days after the last preventive inoculation; the infection appears 
 to have been of a severe type. 
 
 Virus heated to 45 for half an hour proved to have definite 
 immunizing power, but not to conform to the necessary degree of 
 safety (cf. experiments recorded on p. 65). 
 
 Virus heated to 50 seems to meet the requirements of 
 immunizing power and safety better than the others. Further 
 experiments with this virus may lead to more hopeful results. 
 
 (e) Immunization with mixtures of virus and serum containing 
 antibodies. As we shall see later, it is possible to demonstrate the 
 presence of antibodies in the serum of immune monkeys and human 
 beings which, when mixed with virus in vitro, destroy the activity 
 of the latter. It was natural to attempt to produce immunity by the 
 injection of such mixtures. I have had some success in this direc- 
 tion. Flexner and Lewis obtained no result in similar experiments, 
 and so I wish to emphasize the fact that the following experiments 
 are the only ones performed by me along these lines and that they 
 were not performed ad hoc. 
 
 Experiment 1. — The following monkeys were given an intracerebral 
 injection of '6 c.c. of virus No. 11 on March 15, 1910 : — 
 (a) Control monkey No. 41 (Macacus rhesus). 
 March 16-25. — No symptoms. 
 March 26. — Paralysed. 
 
THE FIGHT AGAINST THE DISEASE l6l 
 
 March 28. — Paralysis more marked; then gradual improvement. 
 (Details, see p. 59). 
 
 (b) Monkey No. 30 (Macacus rhesus) had received an intracerebral 
 injection of a mixture of virus and specifically active serum, without any 
 subsequent symptoms, on February 7, 1910. 
 
 Result of the injection on March 15, 1910. — Remained permanently well. 
 
 (c) Monkey No. 31 {Macacus rhesus) received the same preliminary 
 treatment as monkey No. 30. 
 
 Result of infection on March 15. — Remained permanently well. 
 
 Experiment 2. — The following monkeys were given an intracerebral 
 injection of '6 c.c. of virus No. 11 on July 13, 1910 : — 
 
 (a) Control monkey No. 102 (Macacus rhesus). 
 July 13-24.— Well. 
 
 July 25. — Paralysed. 
 
 July 26. — Death. Microscopical appearances typical. (Details on p. 77.) 
 
 (b) Monkey No. 57 (Macacus rhesus) had received an intracerebral 
 injection of a mixture of virus and human serum containing antibodies on 
 May 31, 1910. 
 
 Result of the infection on July 13. — Remained permanently well. 
 
 (c) Monkey No. 60 (Macacus rhesus) had received an intracerebral 
 injection of a mixture of virus and serum containing antibodies (see p. 171). 
 
 Result of the infection on July 13. — Died on July 30 as a result of 
 a cerebral abscess (see p. 52). 
 
 It is remarkable that no changes indicative of poliomyelitis were found 
 in this animal even on July 30. (The control had died on July 26.) 
 
 Experiment 3. — On May 31, 1910, the following monkeys were given 
 an intracerebral injection of '5 c.c. of virus No. 11 : — 
 
 (a) Control monkey No. 58 (Macacus rhesus). 
 June 1-6. — No symptoms. 
 
 June 11. — Paralysed. 
 
 June 13. — Death. Microscopical appearances typical. (Details on p. 77.) 
 
 (b) Monkey No. 39 (Macacus rhesus) received an injection of a mixture 
 of virus and monkey's serum containing antibodies on March 2, 1910, 
 without any subsequent symptoms (see p. 164). 
 
 Result of infection on May 31. — Remained permanently well. 
 
 In my experiments, "therefore, four monkeys (if monkey No. 60 
 is counted the number is five), which had previously received an 
 injection of a mixture of virus and serum containing antibodies, sur- 
 vived an infection which produced paralysis in the controls in the 
 usual way. Landsteiner and Levaditi obtained the same result with 
 a monkey which had been inoculated with such a mixture subcu- 
 taneously; the animal was found to be protected against reinfection, 
 while two control monkeys became paralysed. 
 
 Flexner and Lewis say that they were unable to produce 
 immunity with a mixture of virus and serum ; they suppose that the 
 serum prevents that development of the virus which is necessary 
 for the production of immunity. As far as I can judge from the 
 communications of these authors, the monkeys which they tested 
 had been vaccinated with serum obtained from highly immunized 
 
 11 
 
1 62 EPIDEMIC INFANTILE PARALYSIS 
 
 monkeys. But it is well known that the proportion of virus to 
 antibody is of the greatest importance for success in serum- 
 vaccination. In my experiments, in which serum from convalescent 
 cases was used, a small quantity only of antibody was present in 
 all probability, and thus, by chance, favourable conditions prevailed. 
 
 (£) Immunization during the incubation period. Protective 
 inoculation against rabies stands in a unique position compared with 
 inoculation against other diseases, in that it is used after infection 
 has taken place, i.e., during the incubation period of the disease. 
 That this is possible is explained by the difference between the virus 
 which causes hydrophobia and the virus fixe, used for vaccination. 
 Landsteiner and Levaditi, following Pasteur's method, tried to 
 protect monkeys after they had been given an intracerebral injection 
 of virus. These animals, however, all became paralysed on the 
 eighth day, like the controls. 
 
 Following the same train of thought, Flexner and Lewis tried 
 to immunize monkeys by giving simultaneously an intracerebral 
 injection of fully active virus and a subcutaneous injection of virus 
 heated to 6o° for half an hour, or of virus heated to 55°-57° for one 
 hour. These experiments were without result. The same thing 
 happened in Krause's experiments; simultaneously with, or after, 
 intracerebral injection he gave monkeys his carbolic acid vaccine. 
 Attempts to immunize monkeys during the incubation period have 
 failed so far. 
 
 (rj) The biological connection between poliomyelitis and rabies 
 from the point of view of immunity. Owing to the apparently close 
 relationship between the active agents of rabies and poliomyelitis, 
 and because of the many analogies between the diseases, Land- 
 steiner and Levaditi tried to find out whether there was any 
 biological connection between them from the point of view of 
 immunity. 
 
 Rhesus No. 6 had been proved immune to reinfection after having 
 survived an attack of poliomyelitis, and its serum contained antibody. 
 On May 17 '25 c.c. of rabies virus (virus fixe) was injected. After nine 
 days the animal became paralysed, and died on May 29. The course of the 
 disease was the same in the control. 
 
 This experiment proves the essential biological difference 
 between the two diseases in spite of the many points of analogy 
 between them. 
 
 II.— SPECIFIC ANTIBODIES. 
 
 Fixation of Complement.— It is usual to demonstrate the 
 presence of specific antibodies in the blood of cases of acquired 
 immunity. It is very difficult to be successful in the case of polio- 
 myelitis because the cause of the disease cannot be cultivated, and 
 a large number of reactions, which ordinarily are carried out in a 
 test tube, are impossible. We ourselves began by testing the 
 
THE FIGHT AGAINST THE DISEASE 163 
 
 reaction of fixation of complement, because this is one of the most 
 sensitive reactions and serves to indicate extremely small quantities 
 of antigen and antibodies. 
 
 We used the ordinary procedure; as indicator we used the 
 known hemolytic system (1 c.c. of 5 per cent, sheep's blood 
 corpuscles, well washed; specific hsemolytic amboceptor obtained 
 from rabbits in twice the necessary amount, and fresh guinea-pig 
 serum as complement, also in twice the necessary amount). Extracts 
 of the spinal cord of monkeys and human beings, who were certainly 
 suffering from poliomyelitis, were used as antigen ; we used not only 
 watery extracts, but also antiformin extracts. We made use of the 
 •experience gained by Altmann and Schulz in making the antiformin 
 -extracts (Zeitsch. f. Immunitatsforschung, vol. iii). We examined 
 the blood and cerebrospinal fluid of human beings in various stages 
 of the disease for antibodies which would fix the complement; we 
 also examined the serum of monkeys which had survived infection, 
 and of monkeys which had received repeated large doses of virus 
 for purposes of immunization. I will only mention summarily 
 that the existence of antibodies which would fix the complement was 
 not proved in a single case. We did obtain fixation of the comple- 
 ment by mixing the watery extract with the serum of a sheep which 
 had been treated many times with poliomyelitic spinal cord. How- 
 ever, the serum of this sheep showed fixation of the complement 
 when mixed with a similar extract of the spinal cord of a normal 
 monkey, so that the occurrence of fixation of the complement was 
 ■due merely to a specific reaction between the albumin of the sheep's 
 serum and of the monkey's spinal cord, and it was not a reaction 
 specifically of the virus of poliomyelitis. Starr and Wollstein had 
 already examined the spinal fluid of a large number of patients with 
 the same result. They used spinal cord, nerves, muscles and 
 •extract of the liver from cases of poliomyelitis as antigen. 
 
 Specific HypersensitiveneSS. — We have investigated the ques- 
 tion whether there is any specific hypersensitiveness shown by cases 
 of experimental poliomyelitis analogous to the tuberculin reaction. 
 We investigated the skin particularly. We had found that in tuber- 
 culosis the method of subcutaneous injection gave very reliable 
 results. We injected into the skin of monkeys during the incubation 
 period, directly paralysis set in and during convalescence, 2 c.c. of 
 a 5 per cent, emulsion of monkey's spinal cord containing living or 
 dead (55°) virus. We never had any positive result. Leiner and 
 v. Wiesner also had negative results by this method. 
 
 These negative results in the search for specific antibodies are 
 of importance, because they constitute another analogy between 
 poliomyelitis and rabies. In rabies the reaction of fixation of com- 
 plement has never been obtained even when serum has been used 
 which has been proved, by other methods, to contain antibodies. 
 
 Successful Demonstration of Antibodies.— The antibodies in 
 rabies have been demonstrated by mixing the virus with the serum 
 •of individuals who have undergone specific treatment. On injection 
 
164 EPIDEMIC INFANTILE PARALYSIS 
 
 of this mixture, under certain conditions, it is found to be non- 
 virulent to certain sensitive animals. The necessary conditions are, 
 that the emulsion should be as finely divided as possible (i.e., passed 
 repeatedly through filter paper), and that contact between the virus 
 and the serum should be sufficiently long. 
 
 I mixed virus from poliomyelitic spinal cord, usually of a 
 strength of 5 per cent, and repeatedly filtered through paper, with 
 equal parts of the serum to be investigated; the mixture was kept 
 for one hour at a temperature of 37°. and then for twenty-three 
 hours in an ice-chest or at the temperature of the room. The 
 mixture was given to monkeys as an intracerebral injection of "6 or 
 •8 c.c. The control experiments were made with a similar mixture 
 prepared with serum from a normal monkey; the mixture was 
 allowed to stand for the same length of time, and the same doses 
 were given to normal monkeys by intracerebral injection. The 
 results were as follows : — 
 
 Experiment 1. — The following monkeys received intracerebral injections 
 of '7 c.c. of a mixture of serum and virus Xo. 12 prepared as above : — 
 
 (a) Control monkey Xo. 29 {Macacus rhesus). A mixture containing 
 serum of a normal monkey. 
 
 February 8-14. — Xo symptoms. 
 
 February 15. — Paralysis, which ended in death on the 22nd. (Details, 
 see p. 47-) 
 
 (b) Monkey X'o. 30 (Macacus rhesus). The virus was mixed with serum 
 withdrawn on February 5 from monkey Xo. 6, which had repeatedly been 
 proved to be immune to reinfection (see pp. 151 and 152). 
 
 Result of the infection on February 7. — Monkey Xo. 3 remained per- 
 manently well. 
 
 (c) Monkey Xo. 31 (Macacus rhesus). The virus was mixed with an 
 equal part of a mixture of the sera of monkeys Xos. 9 and 10 (equal parts), 
 which had been proved to be immune (see p. 152). 
 
 Result of the infection on February 7. — Monkey Xo. 31 remained per 
 manentlv well. 
 
 Experiment 2. — On March 2, 1910, the following monkeys received ai> 
 intracerebral injection of a mixture of serum with virus Xo. 12 ('6 c.c.) : — 
 
 (a) Control monkey Xo. 37 (Macacus rhesus). The serum of a normal 
 monkey was used. 
 
 March 3-8. —Well. 
 
 March 9. — Paralysed. 
 
 March 11. — Total paralysis of the hind limbs. 
 
 April 14. — Death from marasmus. (Details, see p. 57.) 
 
 (b) Monkey Xo. 38 (Macacus rhesus). The virus mixed with serum 
 from monkey Xo. 27, which had been unsuccessfully inoculated with killed 
 virus (see pp. 53 and 160). 
 
 March 3-9. — Xo symptoms. 
 
 March 10.— 111. 
 
 March 11. — Paralysed. 
 
 March 12. — Death. (Details, see p. 54.) 
 
 (c) Monkey Xo. 39 (Macacus rhesus). Virus mixed with sera of 
 monkeys Xos. 32 and 34. Monkey Xo. 32 had survived infection on February 
 
THE FIGHT AGAINST THE DISEASE 1 65 
 
 7, 1910, and consequent paralysis (see p. 65); it was immune against re- 
 infection (see p. 159). Monkey No. 34 had received subcutaneous injections 
 of virus heated to 45° on February 7 and 9 for immunizing purposes. 
 
 Result of the injection on March 2. — Monkey No. 39 remained per- 
 manently well. 
 
 These experiments show that serum from monkeys, which 
 have survived paralysis or which have been successfully immunized, 
 when mixed with virus under these conditions, will destroy the 
 infective power of the virus. 
 
 Landsteiner and Levaditi, Leiner and v. Wiesner, Flexner and 
 Lewis have proved by similar methods that specific antibodies are 
 present in antipoliomyelitic serum. Certain differences in the 
 methods used, and particularly in the duration of contact between 
 the virus and the serum, make it necessary to refer more in detail 
 to these experiments. In the first place those of Landsteiner and 
 Levaditi : — 
 
 Experiment 1. — 3 c.c. of the serum of immunized monkeys, the 
 immunity of which had been tested, were mixed with 35 c.c. of virus 
 emulsion filtered through paper; the mixture was allowed to stand for 
 four hours at the room temperature and was then injected into the following 
 animals : — 
 
 (a) Control mandril No. 73 (virus mixed with saline), paralysed in 
 thirteen days, dead in fifteen days. 
 
 (b) Macacus rhesus No. 74 (virus mixed with serum from immune 
 monkey). 
 
 Remained permanently well. 
 
 In the second experiment serum and virus were mixed in the same way, 
 but the mixture was allowed to stand on ice for a night [i.e., at least twelve 
 hours). It was injected into the following : — 
 
 (a) Control monkey No. go {Macacus cynomolgus), virus mixed with 
 saline; paralysed in nine days; microscopical appearances typical. 
 
 (b) Macacus cynomolgus No. 88. Virus mixed with immune serum. 
 Remained well. 
 
 (c) Macacus cynomolgus No. 89. "Virus mixed with immune serum. 
 Remained well. 
 
 Leiner and v. Wiesner found that when a mixture of virus and 
 immune serum was kept for four hours at the temperature of the 
 room, the intracerebral injection caused only slight paresis in 
 monkeys, while control animals became severely ill. After contact 
 of virus and serum for six hours the monkeys remained well and 
 the controls became ill. 
 
 Flexner and Lewis proved that normal monkey serum mixed 
 with the virus had no effect upon it, but that immune serum added 
 to virus, the mixture being- warmed for one hour at 37 and allowed 
 to stand on ice overnight, rendered the virus innocuous. This was 
 practically a corroboration of my own experiments. 
 
 The unanimous verdict of all these authors is that the serum of 
 monkeys which have survived the disease, or which have been 
 successfully immunized against it, when mixed with virus for a 
 
1 66 EPIDEMIC INFANTILE PARALYSIS 
 
 sufficiently long time renders the latter completely innocuous. We 
 do not know how the serum produces this result. Some authors 
 talk simply of an " antimicrobial " serum; but we know of no means 
 to prove that the serum kills the virus in the test-tube. The only 
 reagent which we possess is the body of the living monkey. It is 
 possible that the virus is killed in the test-tube, but it is also possible 
 that it is not killed at all. but merely rendered non-infective because 
 its reproductive power is destroyed. It is going too far to say that 
 the serum is "antimicrobial." However, it is quite certain that 
 the antipoliomyelitic serum prevents infection in some specific way. 
 
 In this instance also we find that the correlation of results 
 obtained in different laboratories enables us to formulate definite 
 general conclusions and renders unnecessary the long series of 
 experiments on various animals, which Krause and Aleinicke 
 consider to be essential. 
 
 It is probable that the antibodies are the cause of the immunity; 
 from the above experiments we see that only sera obtained from 
 immune animals proved capable of abolishing the infectiveness of 
 the virus; serum from normal monkeys, or those in which pre- 
 ventive inoculation had proved unsuccessful, did not have this action 
 (cf. my experiment 2 (b)). 
 
 Flexner and Clark found antibodies in the cerebrospinal fluid 
 sometimes, usually just after recovery from infection. They hold 
 that this is due to the abnormal permeability of the diseased vessels. 
 According to their observations, specific antibodies are present also 
 in the bile of immune monkeys. 
 
 Flexner and Lewis examined the serum of other animals 
 (horses, rabbits and fowls), but found that it had no effect on the 
 activity of the virus. The natural immunity which these animals 
 show towards the virus of poliomyelitis therefore cannot be due to 
 the presence of specific antibodies in their blood. Flexner and 
 Lewis found that normal sheep's serum was slightly active, and 
 they believed that they increased its activity by specific treatment 
 of the animals. Krause proved that the serum of a sheep which 
 had been treated subcutaneously for months with emulsion of polio- 
 myelitis virus, had a specific antipoliomyelitic action (the degree of 
 activity appears to have been small). 
 
 Serum Diagnosis. — Possessing as we do a method of demon- 
 strating the presence of antibodies, it becomes possible to make the 
 attempt to use it for diagnostic purposes. The first question which 
 must be decided is, whether antibodies are present in the serum of 
 patients who have had Heine-Aledin disease. I performed the 
 following experiments with human serum in conjunction with 
 Professor Eduard Muller, who consents to the publication of the 
 results in this place. 
 
 Y\ e first made the following experiment : The mixtures ^i 
 virus and serum were made in an exactly similar way to that used 
 in my experiments with monkeys. The control serum used was 
 taken from a new-born child, whose mother's past history contained 
 no indication of poliomyelitis. 
 
THE FIGHT AGAINST THE DISEASE 1 67 
 
 Experiment 1. — On May 19, 1910, the following monkeys received intra- 
 cerebral injections of mixtures of virus and serum : — 
 
 (a) Control monkey Xo. 56 (Macacus rhesus) was given '4 c.c. of 
 emulsion of virus and '4 c.c. of serum of the new-born child intracerebrally, 
 and simultaneously 5 c.c. of emulsion of virus intraperitoneally. 
 
 May 20-June 1. — Xo symptoms. 
 
 June 2. — Paralysed. 
 
 June 10. — Death (see p. 76). 
 
 (b) Monkey Xo. 55 (Macacus rhesus) injected in a similar manner. The 
 serum of the patient, Alois H., was used in the mixture. 
 
 Result of the injections. — Monkey Xo. 55 remained permanently well. 
 
 A resume of the history of Alois H., aged 23 years (after Ed. Muller) : — 
 
 The child became ill on September 10; fever, rapid pulse, vomiting, 
 headache, and constipation. He cried out when taken hold of : " Leave me 
 alone, that hurts,"' or even when he was only touched. There was marked 
 sweating. At first the case was diagnosed as rickets and intestinal catarrh. 
 During the first few days the child appeared to have difficulty and pain on 
 micturition. 
 
 October 11. — Eyes and cranial nerves normal. Internal organs normal. 
 
 Complete flaccid paralysis of both arms and both legs, said to have 
 appeared on the second day of the illness. Deep reflexes absent in all limbs. 
 
 Abdomen is soft. Epigastric reflexes absent. 
 
 Can sit up only with difficulty, the head rolling in all directions. 
 
 Swab from the throat shows mainly pneumococci, a few colonies of 
 Staphylococcus aureus. Leucocyte count 3,000; blood-film shows nothing 
 abnormal. 
 
 Lumbar puncture: Clear, colourless fluid under high pressure; 
 albumin and sodium chloride present in large amount ; microscopically a 
 few lymphocytes ; cultures made from the fluid all remained sterile. 
 
 Within a week the general condition improved ; the child remained 
 apathetic. Appetite good ; there was a tendency to vomiting and a remark- 
 ably frequent pulse. After three weeks a scarlatiniform rash appeared 
 suddenly on the chest and arms ; no sore throat, no rise of temperature. 
 Eight days later the rash appeared on the thighs and disappeared completely 
 five days later. Definite peeling in small flakes was seen on the parts 
 affected. Sweating remained profuse. The condition of the nervous system 
 remained practically unchanged; some improvement in the arms; the hands 
 and fingers showed some return of voluntary movement. At the end of six 
 weeks, some distal improvement in the legs. Xo reaction of degeneration. 
 
 The flaccid paralysis of the legs remained, and the child died in a 
 marasmic condition at the end of May, 1910. 
 
 Experiment 2. — On July 13, 1900, the following monkeys were injected 
 with mixtures of virus and serum : — 
 
 {a) Control monkey Xo. 102 (Macacus rhesus). Virus mixed with 
 physiological saline. 
 
 July 14-24. — Well. 
 
 July 25. — Paralysed. 
 
 July 26. — Death (see p. 77). 
 
 (b) Monkey Xo. 63 {Macacus rhesus). Virus mixed with serum of 
 Elfrida G. The serum was withdrawn on June 23 and kept on ice. 
 
 Result of the injection on July 13 : Monkey Xo. 63 remained per- 
 manently well. 
 
1 68 EPIDEMIC INFANTILE PARALYSIS 
 
 (c) Monkey Xo. 64 [Macacus rhesus). Virus mixed with serum, of 
 Heinrich P. 
 
 Result of the injections on July 13 : Monkey Xo. 64 remained per- 
 manently well. 
 
 Short abstract of the clinical histories of the two patients : — 
 
 (1) Elfrida G., 8 years old, from Liidenscheid, suffered from infantile 
 paralysis at the age of two. In Xovember, 1908, tendon transplantation 
 performed. 
 
 Condition on June 23, 1910 : Internal organs normal. The whole right 
 leg atrophic; power and muscular tone diminished. The limb feels cold; 
 the patellar, Achillis and plantar reflexes are absent on the right side. 
 Epigastric reflexes present. Power of abdominal muscles good. Talipes 
 equinus on the right side with inversion of the foot (paralysis of the peronei). 
 Xo sensory loss. 
 
 Diagnosis : Old-standing spinal infantile paralysis. 
 
 (2) Heinrich P., 5 years old; from Frankenau. 
 
 In September, 1909, bilateral complete flaccid paralysis of the legs. 
 (Details may be found in Muller's monograph, p. 36.) By Xovember the 
 paralysis had disappeared ; tone of the muscles good ; plantar reflex present. 
 Infantile paralysis recovered from. 
 
 Our experiments show in the first place that normal human 
 serum has no effect on the virus, but that the serum of individuals 
 who have survived an attack of Heine-Medin disease contains specific 
 antibodies just as in the case of monkeys. Antibodies are present 
 even when the paralysis is completely cured, and even so long as 
 six years after the acute illness. 
 
 Netter and Levaditi have paid particular attention to this last 
 point. They allowed their mixtures of virus and serum to stand for 
 three hours at a temperature of 15 and for twelve hours on ice. 
 
 In their experiments serum was taken from the following 
 patients : — 
 
 (a) Girl, aged 3 years, H.-M. disease middle of January, iqiO\ T . . f . 
 )i\ «-• i a J tj at j- j 1 t\ u Z. „ I Iniection of virus 
 
 16) Girl, aged 7. years, H.-M. disease end of December, 1909 J , 
 / \ u j "io ,, „ ,• ... c c j. „ I and serum mix- 
 
 ic) Man, aged 35 years, H.-M. disease beginning or beptem- > . , T , 
 
 w ! „ t> & r ture on ;\T arc h 9 
 
 ber, 1909 
 
 {d) Boy, aged 5 years, H.-M. disease in 1907 
 
 1 910. 
 
 Result. — Control monkey Xo. 66 (virus mixed with normal serum), 
 paralysed in seventeen days, dead on March 30. 
 
 Monkeys injected with virus mixed with serum obtained from cases 
 [a) to [d) all remained well. 
 
 The experiments show that antibodies are present six weeks 
 after the acute illness, and that they are still demonstrable after 
 three years. Xetter and Levaditi arrive at the following important 
 conclusion: The virus was obtained from Landsteiner, i.e., from 
 the Austrian epidemic, while the antibodies were present in the 
 serum taken from patients in France. The activity of the anti- 
 bodies against the Austrian virus shows that the active agent in 
 the two epidemics was the same. Case (d) was a so-called sporadic 
 case, and yet the serum promptly neutralized the virus. This affords 
 the final proof that the sporadic and the epidemic cases belong to 
 
THE FIGHT AGAINST THE DISEASE 1 69 
 
 identically the same disease. Our own experiment 2 (b) proved the 
 same point, the serum being- derived from a sporadic case. These 
 experiments also prove that the demonstration of antibodies may 
 be used as a clinical test. 
 
 Netter and Levaditi give the further interesting facts in rela- 
 tion to the question of the persistence of the antibodies in human 
 beings : — 
 
 Monkeys were injected in a similar manner as in the preceding experi- 
 ments with serum from the following cases : — 
 
 [a) Boy, aged 6i years, H-M disease middle of January, 1910 | 
 (/>) Boy, aged 12 years, H-.M. disease 11 years ago Monkeys injected 
 
 (r) Baby at the breast, brother of case (a), who suffered from j on Aprils, l 9 I0 - 
 an atypical poliomyelitis of the abortive variety J 
 
 Result. — Control monkey (mixture of virus with normal serum), para- 
 lysed in seventeen days, died on April 23. 
 
 Monkeys injected with virus and serum of cases (a) and (c) remained 
 well. 
 
 The monkey injected with virus mixed with serum of case (b) had 
 paralysis limited to the left hind limb and survived. 
 
 Xetter and Levaditi draw the conclusion that antibodies are still 
 present, but in diminished quantity, after eleven years. These 
 observations, together with our own experiment 2 (b) throw much 
 light on the question of duration of immunity discussed above. 
 
 The investigation of Xetter and Levaditi of case (c) shows that 
 specific antibodies are formed in abortive poliomyelitis. Miiller and 
 I were able to bring further evidence on this point. 
 
 On May 31, 1910, the following monkeys received intracerebral injections 
 of a mixture of virus and serum : — 
 
 (a) Control monkey No. 58 (Macacus rhesus). A mixture of virus and 
 serum from a normal new-born child. 
 
 June 1-10. — No symptoms. 
 
 June 11. — Paralysed. 
 
 June 13. — Death (see p. 77). 
 
 (b) Monkey No. 57 (Macacus rhesus). — Mixture of virus and serum of 
 the patient, Erna B. 
 
 Result of the inoculation. — Remained permanently well. 
 Erna B. was a child 2 years old, who suffered from a rudimentary form 
 of poliomyelitis. 
 
 The fact that antibodies are formed even when the poliomyelitis 
 is abortive is of great practical importance. In our own case, for 
 example, the result of the test made the diagnosis certain, which 
 it was not before the test was made. Anderson and Frost were 
 able to prove that atypical poliomyelitis was present in six doubtful 
 cases in the same manner. It is impossible to estimate the value 
 of serum diagnosis in future epidemics. In particular, it will be 
 necessary to find out if antibodies are present in the blood serum of 
 people who live with the sufferer from poliomyelitis, but who are 
 unaffected. In this way many obscure points in the epidemiology 
 of the disease may be made clear. 
 
170 EPIDEMIC INFANTILE PARALYSIS 
 
 In other cases a negative result may be of value, as in the 
 following instance. The patient, Daniel Sell., aged 7, and three of 
 his brothers and sisters suffered from the same symptoms, cough, 
 vomiting, and diarrhoea, without any neurological symptoms. The 
 diagnosis was: Neuritis and acute bronchitis; the suspicion of 
 poliomyelitis cannot be excluded. 
 
 The mixture of the patient's serum and virus No. 11 was made in the 
 usual way and given to monkey No. 61 (Macacus rhesus) by intracerebral 
 injection. 
 
 June 14-17. — Well. 
 
 June 18. — Paralysed. 
 
 June 10. — Death. (Details, see p. 52.) 
 
 In this case the negative result of the test enabled poliomyelitis 
 to be excluded; the diagnosis was not very probable because the 
 patient came from a village in which there were no cases of polio- 
 myelitis. 
 
 Clinical and epidemiological investigation, particularly by 
 Medin, has shown that Strurnpell's old theory was correct, namely, 
 that there are cerebral forms of Heine-Medin disease. But 
 undoubtedly there are also polio-encephalitic processes which are not 
 connected etiologically with Heine-Medin disease. In such cases 
 serum diagnosis may be of much value. The following serves as 
 an example of this : — 
 
 On July 13, iqio, the following monkeys received intracerebral 
 injections : — 
 
 (a) Control monkey No. 102 (Macacus rhesus). — A mixture of virus and 
 saline. 
 
 Death from paralysis on July 26. (See Experiment 2, p. 161.) 
 
 (b) Monkey No. 65 (Macacus rhesus). — A mixture of virus and the 
 serum of George K. 
 
 The result of the injection on July 13. — Monkey No. 65 remained per- 
 manently well. 
 
 Short abstract of the clinical history of George K. — Age 33 years, had 
 infantile paralysis during the first year of life, otherwise no important 
 illness. 
 
 Condition on June 28, 1910. — Internal organs normal. Reflexes all brisk 
 except the pupil reflexes. Patient appears mentally dull. Speech is slow 
 and stammering. Comprehension fairly good. The whole of the muscu- 
 lature on the right side is weaker than on the left (leg, arm, face). 
 
 Diagnosis. — Long-standing cerebral infantile paralysis. 
 
 In this case, therefore, proof was brought forward by means 
 of serum diagnosis that the cerebral form of infantile paralysis is 
 identical from the etiological point of view with the typical spinal 
 form of the disease. Further, in this case antibodies were present 
 in the blood of a patient thirty-two years after he had suffered from 
 the acute attack. 
 
 A number of authors have maintained that the etiology of 
 herpes zoster is the same as that of poliomyelitis. In herpes 
 
THE FIGHT AGAINST THE DISEASE 171 
 
 zoster infiltration of the intervertebral ganglia is found, which is 
 similar to infiltration of these ganglia found in spontaneous and 
 experimental poliomyelitis by Swedish and American authors 
 (Forssner and Sj avail, Strauss, Flexner). We have therefore 
 examined some cases of herpes zoster. 
 
 On June 13, 1910, the following received intracerebral injections : — 
 
 (a) Control monkey No. 59 (Macacus rhesus). — A mixture of virus No. 
 1 1 with serum from a new-born child. 
 
 June 15-21. — Well. 
 
 June 22. — Gastro-intestinal symptoms. 
 
 June 24. — Paralysis. 
 
 Gradual improvement. (Details, see p. 56.) 
 
 (b) Monkey No. 60 (Macacus rhesus). — A mixture of virus No. 11 with 
 serum of the patient, Adam St. 
 
 Result of the infection. — Monkey No. 60 remained permanently well. 
 
 Short abstract of the clinical history of the patient, Adam St., farmer. — 
 Some days ago he had feelings of cold, pains in the knees, and swelling of 
 the glands in the inguinal region ; next day a red rash on the left thigh. 
 Anorexia ; furred tongue. Otherwise no symptoms. Vesicular eruption 
 over a saddle-shaped area on the buttocks. 
 
 Diagnosis. — Herpes zoster. 
 
 We have examined two other patients with herpes zoster by 
 this method. Both monkeys which were injected with a mixture 
 of virus and serum in the usual way remained well (Nos. 104 and 
 105). This did not amount to proof, because unfortunately the 
 control monkey did not become ill either (injected with a mixture 
 of virus and serum from a normal new-born child). Possibly this 
 monkey was one of the few (5 per cent.) which are refractory. 
 We therefore cannot lay much stress on this experiment, although 
 the results are of interest, and the subject must be investigated 
 more fully. 
 
 W T e are convinced that this method will prove of use in many 
 other doubtful conditions, e.g., in some cases of facial palsy. 
 Further, it may be applied in order to determine whether the cases 
 of poliomyelitis which occur with measles and scarlet fever are 
 cases of true Heine-Medin disease; whether they are due to acci- 
 dental double infection, or whether there is some other etiological 
 factor at work. In the differential diagnosis of poliomyelitis and 
 cerebrospinal meningitis the serum test will be of the greatest value. 
 
 The clinician can call to mind many other conditions which are, 
 as yet, little understood. We are only at the beginning of such 
 investigations, and the preceding research is meant chiefly to indicate 
 the importance of such investigation and the methods by which it 
 may be carried out. 
 
 Serum Therapy. — It would be still more gratifying if the anti- 
 bodies could be made use of in therapeutics as well as for purposes 
 of diagnosis. Experience with the virus of rabies does not seem 
 to hold out much hope in this direction; Kraus has shown that 
 although the antibodies of this disease prove very efficacious in 
 
I72 EPIDEMIC INFANTILE PARALYSIS 
 
 vitro they have no therapeutic effect either as a preventive or a 
 curative measure. On the other hand, Heine-Medin disease in man 
 runs a much more benign course than rabies. The lack of any other 
 means of treating the disease during the acute stage is an argument 
 in favour of trying the effect of treatment with antibodies. I have 
 no experience in this matter; my experiments came to an end owing 
 to lack of material just when I had reached the stage of investiga- 
 tion of the therapeutic action of the serum. 
 
 Leiner and v. Wiesner gave monkeys simultaneously intra- 
 cerebral injections of virus and intraperitoneal injections of large 
 quantities of serum containing antibodies. The monkeys so treated 
 became paralysed quite as quickly and as severely as the controls. 
 Subcutaneous and intraspinal injection of the serum also proved 
 useless. 
 
 Levaditi and Landsteiner had similar negative results : — 
 
 Monkeys No. 79 (Mangabey) and No. 80 [Callitrichus) were infected on 
 January 19, 1910. Monkey No. 79 received on January 19, 20, and 24 5 c.c, 
 10 c.c, and 5 c.c. of the serum of a monkey which had survived an attack of 
 poliomyelitis. Both monkeys became paralysed in five days. Simultaneous 
 intraspinal injection of serum and intracerebral infection also proved useless. 
 
 Monkeys Nos. 92 and 93 [Rhesus) were given intracerebral infection on 
 February 12, 1910. 
 
 Monkey No. 92 received 2 c.c. of the serum of a highly immunized 
 monkey into the theca on February 12, 13, and 15. Monkey No. 92, together 
 with the control monkey, became paralysed on February 17. 
 
 Intraperitoneal and intraspinal injections of the serum thus 
 proved to be of no curative value. Kraus found that his specifically 
 active sheep serum had no prophylactic effect (see p. 166). 
 
 The outlook for serum therapy does not seem bright. Flexner 
 and Lewis are the only authors who have obtained any positive 
 results. It is true that serum injected into the theca had no effect 
 on monkeys which had been infected by intracerebral injection, even 
 when treatment was begun very shortly after infection. But when 
 the monkeys were infected in a way more approaching the natural 
 method, according to these authors, the serum was found to exert 
 a definite influence on the course of the disease. Monkeys were 
 infected through the scarified mucous membrane of the throat, and 
 were given repeated intraspinal injections of serum, beginning not 
 later than twenty-four hours after infection; in these animals the 
 incubation period of the disease was found to be as long as twenty- 
 six days, while the control monkeys became paralysed in from nine 
 to eleven days. Flexner and Lewis suggest that if treatment had 
 been carried on longer the occurrence of paralysis might have been 
 prevented. 
 
 They obtained these results not only with the serum of monkeys 
 which had survived the disease, but also with serum from monkeys 
 which had been artificially immunized and from human beings who 
 had suffered from the disease. They hope to raise the antibody 
 
THE FIGHT AGAINST THE DISEASE 1 73 
 
 content of the serum by specific treatment and thus to provide a 
 serum of therapeutic value. They consider that Heine-Aledin 
 disease produced artificially in monkeys is a much more serious 
 disease than that occurring naturally in man. On the other hand,, 
 we must remember that we are not in a position to use the serum 
 so early in the disease in man as Flexner and Lewis were able to in 
 monkeys. 
 
 The only experiment carried out with human serum in man, as 
 far as I know, was performed by Xobecourt and Darre. They gave 
 an intraspinal injection of the serum, and state that symptoms of 
 marked meningeal irritation set in three hours after the injection 
 and continued for several days, but that no definite effect on the 
 course of the paralysis could be observed. Considering how extra- 
 ordinarily variable the course of the disease is, and how impossible 
 it is to give a prognosis from the symptoms of the prodromal stage, 
 it is evident that the value of serum therapy can be established only 
 by means of a very large collection of statistics. At present the 
 question is still in the experimental stage. 
 
 [Xetter, Gendron, and Touraine report that the administration 
 of serum from an old case of poliomyelitis into four acute cases 
 resulted in improvement of three and the death of one case. — 
 Translator.] 
 
 III.— EXPERIMENTS WITH DRUGS. 
 
 Fermi stated that the course of rabies, produced artificially in 
 rabbits, was influenced in a favourable way by certain dyes, particu- 
 larly by Trypan red. I therefore made some experiments on 
 monkeys with this substance, but they were quite unsuccessful. 
 
 Landsteiner and Levaditi used other substances, firstly 
 arsacetin : — 
 
 Two Macacus monkeys received, on the same day and in the same 
 manner, intracerebral and intraperitoneal injections. The control became 
 ill in seven days, and paralysed in eight. The other monkey was given 
 subcutaneous injections of from '075 to '2 gr. arsacetin on the third, 
 fifth, and sixth days after infection. It became ill on the seventh day and 
 paralysed on the eighth. 
 
 In a similar way they used arsenophenylglycin. 
 
 Two Macacus monkeys were infected in the same way as in the preceding 
 experiment. The control became paralysed in twelve days. The other 
 monkey received a subcutaneous injection of '3 gr. arsenophenylglycin at 
 the same time as it was infected. It became ill six days afterwards, and was 
 completely paralysed in seven days. 
 
 Radium and X-rays proved equally useless both for prevention 
 and cure. 
 
 Flexner and Clark recently turned their attention towards 
 urotropin. Cushing and Crowe have shown that urotropin injected 
 
174 EPIDEMIC INFANTILE PARALYSIS 
 
 subcutaneously passes to the cerebrospinal fluid, and they have used 
 this drug as a prophylactic antiseptic in their operations on the brain 
 and spinal cord. Moris in Baltimore is said to have used urotropin 
 with success in poliomyelitis. Flexner and Clark therefore used 
 this drug in the case of monkeys. The animals took it well, and 
 it appeared in the cerebrospinal fluid. These authors infected 
 monkeys which had been treated with urotropin, and they continued 
 the treatment. In some cases the period of incubation was pro- 
 longed to twenty-four days, instead of the usual six to eight days. 
 They hope to achieve better results by combining serum treatment 
 with the administration of urotropin. 
 
 In any case, these American experiments show that a certain 
 amount of therapeutic effect can be produced on acute poliomyelitis. 
 So far, the experiments have only been carried out in animals and 
 have been protective, and not curative, in character. Both serum 
 and urotropin had no effect on poliomyelitis in monkeys when the 
 disease had once begun. In the absence of any known method of 
 combating the disease they deserve consideration. 
 
 Other therapeutic measures are purely symptomatic and it must 
 be left to the clinician to judge of their usefulness (rest, careful 
 nursing, plaster jacket (Hohmann), even a plaster of Paris bed 
 (Machol), sodium salicylate, antipyrin, aspirin, phenacetin, &c). 
 Lumbar puncture appears to me to be a rational method of treat- 
 ment, because I have found increase of fluid sometimes in monkeys. 
 
 It is not within my province to judge of the purely physical 
 methods necessary during the period of convalescence (baths, active 
 and passive movements, electrical treatment, &c), which are all 
 directed towards the prevention of contractures, nor of the ortho- 
 paedic treatment which may become necessary at a later stage. 
 
 IV. —PROPHYLAXIS. 
 
 The methods to be adopted for prophylaxis against the disease 
 are all the more important because we possess no means of in- 
 fluencing the disease when once started. We are driven to adopt 
 special measures against infantile paralysis, not only by humane 
 reasons, caused by the miserable spectacle of the paralysed children 
 themselves, but also by purely economic considerations. As Eduard 
 Muller says, the disease is more to be feared than many other 
 infectious diseases of childhood, because the majority of those who 
 survive remain paralysed; their wage-earning capacity is diminished 
 or destroyed, and they remain chronic invalids. Heine-Medin 
 disease produces a large number of persons who are physically unfit 
 and are a burden to the State. Although the truth of this is obvious, 
 it seems to me necessary to write it, because I have heard even 
 physicians say, that the small number of persons affected by the 
 disease does not justify any special measures. It is true that so 
 far we have not been visited by an epidemic on the same scale as 
 those in Norway and Sweden, but this may happen at any time. 
 
THE FIGHT AGAINST THE DISEASE 175 
 
 Even from the humane standpoint alone, it is our duty to take 
 measures for an efficient prophylaxis. The feeling, often expressed 
 by mothers during our own small epidemic, that they would rather 
 that their children should suffer from a disease more dangerous to 
 life than from infantile paralysis, is based on a very sure and 
 instinctive appreciation of the consequences. 
 
 In the face of the recognized necessity for efficient prophylaxis, 
 it is particularly painful to have to realize how little we know of 
 the usefulness of the measures proposed, and how difficult it is to 
 carry them out. The following suggestions are put forward with 
 full knowledge that they are not in any sense final, and that they 
 will need revision and correction when more is known of the nature 
 and mode of occurrence of the disease. 
 
 Private Prophylaxis. — It will be useful to distinguish between 
 the advice which may be given by the private practitioner and the 
 measures which may be taken by the State. Both must depend 
 upon the result of studies in the epidemiology and pathogeny of 
 the disease. Wickman has proved that the disease is transmitted 
 from one human being to another; consequently all contact with 
 persons who may be carriers of the virus should be avoided. The 
 patient should be isolated, and he should be looked after by only 
 one person, if possible. This will not be enough to stop all possi- 
 bility of further infection. We know from experience that in 
 epidemics the virus is transmitted more frequently by persons 
 suffering from the slight, abortive type of the disease, or by healthy 
 carriers, than by the patient himself. Isolation of the patient must 
 not be omitted on this account, because he may at any time become 
 the source of spread of infection, but it is impossible to isolate all 
 the persons around him. We possess no practicable method of 
 separating those who are infected from those who are not. The 
 method of serum diagnosis cannot be used extensively, because it 
 would be too costly and because the result of the test would be 
 known too late to be of any use. All we can do is to warn those 
 who have been in contact with the patient that they may carry 
 the infection to other people, and to advise them to avoid all com- 
 munication as far as possible. For how long this should be done 
 I shall discuss later. Unfortunately such advice is rarely followed. 
 
 Careful cleansing of the mouth is clearly of importance, when 
 we consider that the virus gains entrance in all probability through 
 the mucous membrane of the mouth, throat, and alimentary canal. 
 For this purpose I advise the use of a i per cent, solution of per- 
 hydrol because of its disinfectant action on the virus of polio- 
 myelitis (cf. Chapter III). The mechanical cleansing effect of this 
 preparation is of great use because, during the act of gargling or 
 rinsing the mouth, the contact between the virus and the drug is 
 necessarily short. Preparations of menthol have a destructive effect 
 upon the virus, but thymol, which is much used as a mouth-wash, 
 has no effect. In all these measures any excessively active use 
 should be avoided, in order that the mucous membrane may not 
 
I 76 EPIDEMIC INFANTILE PARALYSIS 
 
 be damaged. Experimental experience shows that the presence of 
 any lesion of the mucous membrane renders the entrance of the 
 virus much more easy. 
 
 In this connection I may refer once again to the greater in- 
 cidence of the disease during the first two years of life. It is 
 possible that there is a germ of truth in the idea of the older 
 English physicians, which Heine adopted, that troubles of dentition 
 have some etiological significance; there is no doubt that lesions 
 of the mucous membrane are very frequently present at that age. 
 The greater permeability of the mucous membranes, which is 
 physiological in infants, must not be forgotten. Such measures as 
 are taken to prevent entry of the virus from the alimentary tract 
 are all based upon the avoidance of lesions of the mucous membrane. 
 Errors in diet should be avoided. Articles of food do not convey 
 the infection, nor can water be blamed. Milk from an infected 
 house may be contaminated (Wickman), but milk is usually boiled 
 before it is taken nowadays. Xervous persons may be reassured by 
 telling them that a temperature of 6o° is sufficient to destroy the 
 virus. 
 
 In making further regulations to prevent the spread of infection 
 from the patient or from people in contact with him, we must use 
 our experience in connection with the excretion of the virus. Un- 
 fortunately our knowledge is still limited in this respect. Experi- 
 ments with monkeys have shown that virus is found in the nasal 
 mucous membrane, but it has never been demonstrated in the nasal 
 secretion. As we have no definite knowledge it would be wiser to do 
 too much rather than too little. When asked, I always advise the 
 patient and all persons who come in contact with him in any way 
 to cleanse the mouth and throat with the utmost care, because of 
 eventual spread of the disease by the secretion. 
 
 How long the patient and the " carriers " remain infectious it 
 is impossible to say. 
 
 Osgood and Lucus found' virus in the mucous membrane of the throat in 
 monkeys six months after intracerebral injection. At that time they were 
 able to show that virus had already disappeared from the central nervous 
 system. If this is also correct for human beings it explains many " sporadic " 
 cases, but it emphasizes the necessity for disinfection of the mouth as a 
 prophylactic measure. 
 
 Medical men should practise the most careful prophylaxis, they 
 are peculiarly liable to act as carriers of the virus. It is advisable 
 to disinfect the faeces, vomit, and urine of the patient. A 2 per 
 cent, solution of potassium permanganate destroys the virus, and 
 solutions of a high degree of concentration will disinfect the dejecta. 
 The underlinen and bedclothes, and particularly the- pocket handker- 
 chiefs, of the patient must be disinfected; ordinary boiling in the 
 wash is sufficient owing to the peculiar sensitiveness to heat of the 
 virus. The foregoing measures must be used also by the nurse. 
 
 It has been found that the house in which cases of poliomyelitis 
 
THE FIGHT AGAINST THE DISEASE 177 
 
 have lived may retain the infection. In most instances in which 
 this is said to have happened it is probable that the virus was 
 conveyed by direct contact with a human being". However, the 
 possibility cannot be excluded that virus was given off in some 
 secretion or excretion from the patient and remained active owing 
 to its powers of resistance. Wickman brought forward some 
 evidence in support of this view. It is therefore advisable to carry 
 out a disinfection of the house. We have tested the value of 
 formalin for this purpose. 
 
 The experiment was carried out in the usual way by means of Flugge's 
 Breslau apparatus. The dimensions of the room chosen were 4/93 x 3*4 X3"84 
 metres. The formalin and water necessary were calculated according to 
 Flugge's tables. The poliomyelitis virus was exposed in the middle of the 
 room in an open Petri dish ; it was obtained by drying the spinal cord of a 
 monkey suffering from poliomyelitis in vacuo and rubbing it down in a 
 mortar. Silk threads covered with the spores of anthrax were placed close 
 to the dish as a control. The formaldehyde was allowed to act for seven 
 and a half hours. Culture tubes inoculated with the anthrax spores which 
 had been exposed to the formalin vapour showed no signs of growth in thirty 
 days. Tubes inoculated from threads which had not been thus exposed 
 showed definite growth in twenty-four hours. Monkey No. 35 was given an 
 intracerebral injection of '5 c.c. of a 5 per cent, emulsion of the spinal cord 
 exposed to the formalin. At the same time monkey No. 36 received '5 c.c. of 
 a 5 per cent, emulsion of the spinal cord not so exposed. Monkey No. 36 
 become paralysed after fourteen days, and died on the seventeenth day after 
 injection. Monkey No. 35 remained well permanently. 
 
 The usual disinfection with formalin is therefore sufficient to 
 destroy the virus under these conditions. It is to be supposed that 
 other modern methods of disinfecting rooms, when carried out in 
 the same energetic way, will prove equally efficacious. 
 
 State Regulation. — It remains to be seen in what way pro- 
 phylaxis may be furthered by the State. I believe that notification 
 is of the first importance ; Eduard Midler also agrees with me that it 
 should be carried out not only in times of epidemic, but always. 
 Quite apart from the usefulness of this measure in making known 
 the number of sporadic cases which occur, and thus keeping the 
 disease before the minds of practitioners even when there is no 
 epidemic, it will enable us to take steps immediately a case occurs 
 and even prevent the development of an epidemic by prophylactic 
 means in some instances. It is very much to be hoped that some 
 reliable method of early diagnosis will be discovered. Flexner's 
 proposal, that lumbar puncture should be used early for diagnostic 
 purposes, should be more widely followed. In one case Flexner 
 was able to assist materially towards a diagnosis by discovering 
 an increase in the quantity of albumin present and an absence of 
 bacteria. 
 
 For the rest, we shall do well to proceed cautiously in intro- 
 ducing any further State regulation of the disease. Compulsory 
 isolation is not justifiable in the present state of our knowledge. 
 
 12 
 
iyg EPIDEMIC INFANTILE PARALYSIS 
 
 For the same reason I do not think it necessary that the public 
 should be alarmed by the introduction of compulsory disinfection 
 of clothes, household linen, and of rooms. Muller rightly draws 
 attention to the damage to property which this entails, and to the 
 loss which results from declaring a place of business to be infec- 
 tious. Although we can ignore such considerations when dealing 
 with the subject from the purely hygienic standpoint, yet from the 
 practical point of view they are of very considerable importance. 
 On the other hand, the physician in charge of a case may do much 
 by impressing on the relatives, in a tactful way, the importance 
 of simple, practicable prophylactic measures. The uniformed 
 inspector, carrying out these proceedings in as conspicuous a way 
 as possible, is not a sight we should wish to see. 
 
 In another direction the sanitary authorities may well take 
 action. The brothers and sisters of children suffering from the 
 disease should be forbidden to attend school for a period of some 
 weeks (unfortunately we cannot say exactly for how long). In 
 times of epidemic the schools should be closed. The objection has 
 been raised to this, that the children meet at play if they are not at 
 school. I do not think that this is relevant, because it is well 
 known that children from all parts of the town do not flock to one 
 place to play, as they do in the case of the school. Wickman's 
 experience at Trastena has proved how the school favours the 
 spread of infection. During epidemics children should not be 
 allowed to attend church (Muller); the evil practice of permitting 
 children to attend the funerals of comrades who have died of Heine- 
 Medin disease should be stopped; on such occasions contact with the 
 house and with the relatives is usually impossible to avoid. Vac- 
 cination should not be performed during an epidemic, and no 
 children's parties should be given. 
 
 It is the duty of the sanitary authorities to give full information 
 concerning the measures which are considered advisable to all 
 doctors in some suitable form. 
 
 This represents all that it is wise to do at the present time 
 in fighting Heine-Medin disease along hygienic lines. If we carry 
 out these measures we shall feel at least that we have done our 
 duty. Only practical experience can tell us whether thereby we 
 really reach the virus. 
 
 CONCLUSION. 
 
 The attempt made in this book to give a comprehensive descrip- 
 tion of Heine-Medin disease shows how impossible it is to do so, 
 in spite of the many remarkable advances which have been made 
 during the last few years. The study of poliomyelitis provides us 
 with another example of the manner in which additions to our 
 knowledge make us conscious of further and further regions of the 
 unknown. 
 
 The clinical aspect of the problem may be regarded as having 
 
THE FIGHT AGAINST THE DISEASE 179 
 
 been investigated almost in its entirety, thanks to the labours of 
 Heine, Medin, and Wickman. Observation of the last great 
 epidemics has shown that there is not much more to be discovered 
 in that direction. There is one important gap, however, which 
 remains to be filled in, the discovery of a certain means of early 
 diagnosis. The studies of Eduard Miiller show that progress is 
 possible (he lays stress on the heavy perspiration, the hyperesthesia, 
 and the leucopeniaj. 
 
 From the pathological point of view the study of the disease 
 is complete, except in so far as refinements of microscopical methods 
 may yield fresh discoveries. In spite of the investigations of 
 Wickman, and in spite of the results obtained by the experimental 
 method, the question of the pathogenesis of the disease remains 
 obscure and debatable on many points. Systematic experiments 
 with animals will do much to make clear this part of the subject. 
 
 I have tried to emphasize the many points in the epidemiology 
 of the disease which are still doubtful, even after Wickman's 
 researches. We will not hope that opportunities will arise in which 
 we shall be able to study the epidemiology on a large scale; but 
 we may hope that, if our fears are realized, all will be done which 
 is possible to furnish us with new weapons for prophylaxis. 
 
 The main object of this book was to bring forward proofs that 
 the method of experiment with animals, the most recent branch of 
 research, is able not only to confirm the results obtained by the 
 older methods of investigation, but also to throw fresh light upon 
 them and to yield new results in its turn. If the reader should 
 feel disappointed that the actual results are not larger and more 
 important than he finds them, I would ask him to consider that 
 this method is still young, and that the peculiar characteristics of 
 the only animal which is suitable for the experiments limit the 
 range and variety of the investigations very strictly. This is surely 
 a field in which the authorities might render practical assistance, 
 in order that the therapeutics of this pest — until now the most 
 obscure chapter in poliomyelitis — may come to be understood. 
 There is no doubt that the answer to many unsolved problems will 
 be given ultimately by experimental research. 
 
 May the experimental study of Heine-Medin disease be in a 
 position to fulfil the nobile officium, which devolves upon it from 
 the great series of pioneers named in the first chapter of this book, 
 who have brought our knowledge to its present pitch by other 
 means. The study of their works recalls to one's mind the com- 
 parison made by Goethe, by which he used to express the sensation 
 which seized him while studying the profound writings of Kant. 
 They give one the sensation as of entering a brightly illuminated 
 room. 
 
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 EXGLAXD, F. A record of some cases of epidemic paralysis occurring in 
 Hampshire. Brit. Med. Journ., Dec. 3, 191 1. 
 
 ERB, AA~. Uber akute Spinallahmung bei Erwachsenen und uber verwandte 
 spinale Erkrankungen. Arch. f. Psvch. und Xervenkrankh. , 5, 1875^ 
 p. 758. " . 
 
 — Uber Modifikationen der partiellen Entartungsreaktion und liber das 
 
 Vorkommen der chron. atroph. Spinallahmung beim Kinde. X T eurol. 
 Zentralbl., 18S3, Xo. 8, p. 169. 
 
184 EPIDEMIC INFANTILE PARALYSIS 
 
 ERB, W. Zur Lehre von der Unfallserkrankungen des Riickenmarks. Uber 
 Poliomyelitis ant. chron. nach Trauma. Deutsche Zeitschr. f. 
 Xervenheilk., 11, p. 122. 
 
 — Poliomyelitis acuta superior. Deutsche med. Wochenschr., 1906. 
 ESHXER. A possible second attack of acute anterior poliomyelitis in the 
 
 same patient. Med. Record, 13, 1910. 
 
 Farrar. Outbreaks of disease affecting- the cerebrospinal system in the 
 
 Midland Counties and Dorsetshire in 1910. Report to L.G.B. on 
 
 Public Health. New Series, Xo. 61, 1912. 
 Fetra. Early symptoms in sixty-three cases of the recent epidemic of 
 
 Poliomyelitis. Arch, of Ped._, May, 1909. 
 FLEXXER. The contribution of experimental to human poliomyelitis. 
 
 Journ. of Amer. Med. Assoc, Sept. 24, 1910. 
 
 — The control of epidemic poliomyelitis. Amer. Journ. of Dis. of 
 
 Children, August, 191 1, 2. 
 — ■ Experimental poliomyelitis. Folia Serologica, vii, 191 1, p. 1101. 
 FLEXXER and CLARK. Experimental poliomyelitis in monkeys. Journ. 
 of Amer. Med. Assoc, 56, xo. 7, Feb. 18, 1911. 
 
 — Experimental poliomyelitis. Ibid., Nov. 11, 191 1. 
 
 — Contamination of the fly with poliomyelitis virus. Ibid., June 10, 191 1. 
 Flexxer and LEWIS. The transmission of acute poliomyelitis to monkeys. 
 
 Journ. Amer. Med. Assoc, 53, 1909; 20, Nov. 13, 1909. 
 
 — The transmission of acute poliomyelitis to monkeys. Ibid., 53, 1909; 
 
 23, Dec. 4, 1909. 
 
 — The nature of the virus of epidemic poliomyelitis. Ibid., 53, 1909; 25, 
 
 Dec. iS, 1909. 
 
 — Uber experimentell erzeugte akute Poliomyelitis bei Affen und die 
 
 Xatur ihres Erregers. Munch, med. AVochenschr., 2, 1910. 
 
 — Epidemic poliomyelitis in monkeys. Journ. of Amer. Med. Assoc, 
 
 Jan. 1, 1910. 
 
 — Epidemic poliomyelitis in monkeys. A mode of spontaneous infection. 
 
 Ibid., Feb. 12, 1910. 
 
 — Experimental epidemic poliomyelitis in monkeys. Ibid., April 2, 1910. 
 
 — Experimental epidemic poliomyelitis in monkeys. Journ. of Experi- 
 
 ment. Medic, 12, 2, 1910. 
 
 — Experimental epidemic poliomyelitis in monkeys. Journ. of Amer. 
 
 Med. Assoc, 54, Xo. 22. 
 
 — Experimental epidemic poliomyelitis in monkeys. Ibid., 55, 1910. 
 Flexxer, Peabody, and Draper. Epidemic poliomyelitis. The visceral 
 
 lesions of a human case. Journ. of Amer. Med Assoc, Jan. 13, 1912. 
 
 Foerster. Ein Fall von Poliomyelitis im obersten Halsmark. Allg. med. 
 Zentralzeitung, 1902. 
 
 — Zur symptomatologie der Poliomyelitis acuta anterior. Berl. klin. 
 
 Wochenschr., 49, 1909. 
 Forbes. A note on the cerebrospinal fluid in acute poliomyelitis. Lancet, 
 
 18 Nov., 1911. 
 Forssxer and SjOVALL. Uber die Poliomyelitis acuta samt einem Beitrag 
 
 zur Xeuronophagiefrage. Zeitschr. f. klin. Med., 1907. 
 FOX. The pathogenesis of poliomyelitis. Zentralbl. f. Bakt. Abt. 1, 
 
 Ref. 49, Heft, 20-21. 
 Fraexkel, A. Demonstration von mikroskopischen Praparaten eines Falles 
 
 von spinaler Kinderlahmung. Verein f. innere Med. in Berlin, Nov. 
 
 19, 1906. Deutsche med. Wochenschr., 2, 1907. 
 V. Fraxkl-Hochwart. Uber die gegenswartige Poliomyelitis-Epidemie in 
 
 Wien. Munch, med Wochenschr., 49, 1908. 
 Freedmax. Acute anterior poliomyelitis. Cleveland Med. Journ., 1912, 
 
 Xo. 9. 
 FREY. Uber temporare Lahmungen, usw. Berl. klin. AVochenschr., 1874, 
 
 : "3- 
 FRIEDJUXG. Zur Kenntniss der Poliomyelitis acuta anterior. AA ien. med. 
 
 Wochenschr., 39, 1909. 
 FRIEDLAXDER. tiber A'erkalkung der Ganglionzellen. ATrchow's Archiv. 
 
 88, 1882. 
 Frissell. Poliomyelitis anterior epidemica. Journ. of Amer. Med. Assoc. 
 
 Mar. 4, 191 1. 
 
LITERATURE 1 85 
 
 FROST. Conferences on epidemic poliomyelitis of the meeting of the 
 American Public Health Association. Milwaukee, Sep., igio. Public 
 Health Reports, 1910, 41. 
 
 — The field of investigation of epidemic poliomyelitis. Ibid., 25, 1910, 
 
 46. 
 Ft'RXTRATT. Uber Poliomyelitisepidemien mit besonderer Beriicksichtigung 
 der diesjahrigen Epidemie in Steiermark. Das osterreiche Sanitats- 
 wesen, Jahrg. xxi, igog; Beil. zu Xo. 49, p. 79. 
 
 Garrow. Brit. Med. Journ. , igio, vol. ii (suppl., p. 393). 
 
 GASTERS. Vorlaiifige Mitteilung uber anscheinend epidemisches Auftreten 
 
 von Poliomyelitis anterior, der sog. Heine-Medinschen Krankheit. 
 
 Zeitschr. f. Med.-Beamte, 17, igog. 
 GAUJOUX, Emile and EUGEXE. De l'authenticite des epidemies recentes de 
 
 paralysie infantile. Gaz. des hopit., 191 1, Xos. 5 and 6. 
 VAX GEHUCHTEN. Pol. on Polynevrite. Un cas de paralysie segmentaire. 
 
 Annales de la Soc. beige de Xeurol., iSgg, Xo. 6. 
 
 — La poliomyelite anterieure aigue de l'adulte. Arch, de Xeurol., 1903, 
 
 16, p. 331- 
 
 — Cas de poliomyelite anterieure aigue de l'adulte. X'evraxe, 1904. 
 Geirsvold. Epidemisk (i poliomyelit.," Bacteriologiske undersogelsor. 
 
 X'orsk Mag. for Laegevid., Dez., 1905, S. 1280. 
 GELMA. Pari, spin infant., reprise tardive d"amyotrophie. Rev. neurol., 
 
 igi2, Xo. 3. 
 GlBXEY and WALLACE. The recent epidemic of poliomyelitis. Journ. of 
 
 Amer. Med. Assoc, 4g, 1907, 25. 
 Gilbert and Liox. Les paralysies produites par le bacille d'Escherich. 
 
 Compt. rend, de la Biol., i8g2. 
 GIXS. Ein Beitrag zur Poliomyelitisfrage nebst Beschreibunf eines neuen 
 
 fur A'ersuch am Affen geeigneten Kafigs. Zentralbl. f. Bakt., Abt. 1, 
 
 59, 1911, Heft 4. 
 GlOSEFFl. Die spinale Kinderlahmung in unserer adnatischen Region. 
 
 Revista di clinica pediatria, 191 1, 8. 
 GOLDSCHEIDER. Uber Poliomyelitis anterior. Verein f. innere Med. zu 
 
 Berlin, Jan. 2, 1893; Jan. 23, 1893; Berl. klm. AVochenschr., 16 
 __ and 30, 1893. 
 — ■ Uber Poliomyelitis. Zeitschr. f. klin. Med., 23, 1893. 
 Goldscheider and Brasch. Poliomyelitis. Handb. d. path. Anat. d. 
 
 Xervensystems. Berlin, 1903. 
 Gombault. Xotes sur un cas de paralysie spin, de l'adulte suivi d'autopsie. 
 
 Arch, de physiol. norm, et pathol., 1873. 
 GOSSAGE. The etiology of infantile paralysis. Amer. Journ. of Med. Sc, 
 
 1902, p. 789. 
 Gowers. A manual of diseases of the nervous system. Second edition, 1. 
 
 London, 1892. 
 
 — A case of anterior poliomyelitis and multiple neuritis. The Clinical 
 
 Society's Transactions, iSg3. 
 
 Grawitz. Ein Fall von Poliomyelitis acuta bei einer Erwachsenen. Berl. 
 klin. Wochenschr., 12, i8g6. 
 
 GREGOR and Hopper. Clinical observations on an epidemic of acute polio- 
 myelitis in Cornwall. Proc. Row Soc. Med. (Clin. Sec, p. 28), Nov., 
 191 1. Brit. Med. Journ., Xov. 4, ign. 
 
 GROBER. Zu der rheinisch-westfalischen Epidemie von spinaler Kinder- 
 lahmung. Med. Klin. 47, igog. 
 
 — Die akute epidemische Kinderlahmung. Fortschritte d. deutsch. 
 
 Klinik, igio. 
 GROSGEORGES. La poliomyelite dans l'An-jou. These de Paris, ign. 
 GUTNON and RlST. Deux cas de poliomyelite anterieure aigue sans reaction 
 
 meningee cytologique chez un frere et une sceur. Compt. rend, de la 
 
 soc. des hopit. de Paris, 1903. 
 GUMPERTZ. Uber einen ungewohnlichen Fall von Poliomyelitis ant. ac. 
 adult, auf infectioser Grundlage. Berl. klin. Wochenschr., 16, igoo. 
 
 Hagexbach. Uber Poliomyelitisepidemien in der Schweiz. Korrespon- 
 
 denzbl. f. Schweiz. Arzte, Jahrg. 40, Heft 33-36. 
 Harbitz, F. Poliomyelitis-Epidemien. Tidskrift f. d. orske laegefore- 
 
 ning. N.F., igo6, Jahrg. 16, S. 82. 
 
1 86 EPIDEMIC INFANTILE PARALYSIS 
 
 HARBITZ and Scheel. Pathologisch-anatomische Untersuchungen uber akute 
 Poliomyelitis und verwandte Krankheiten von den Epidemien in 
 Norwegen 1Q03 bis igo6. Christiania, 1907. 
 — Akute Poliomyelitis und verwandte Krankheiten. Pathologisch- 
 anatomische Untersuchungen aus den Epidemien in Norwegen 1903 
 bis 1906. Deutsche med. Wochenschr., 48, 1907. 
 — ■ — ■ Epidemic acute Poliomyelitis in Norway in the years 1903-1906. 
 Journ. of Amer. Med. Assoc, 49, 1907, No. 17. 
 — The microbe of poliomyelitis. Ibid., 50, 1908, 4. 
 
 HEIMANN. Clinical study of anterior poliomyelitis. Arch, of Ped., 1909. 
 
 Heine, J. Beobachtungen iiber Lahmungszustande der unteren extremitaten 
 und deren Behandlung. Stuttgart, 1840. 
 — Spinale Kinderlahmung. 2 Aufl. , Stuttgart, i860. 
 
 Hewitt. On acute poliomyelitis (Heine-Medin disease). Brit Med. Journ., 
 Mar. 30, 1912. 
 
 HlGIER. Zur klinik der Schweissanomalien bei Poliomyelitis ant. (Kinder- 
 lahmung^ und post. (Herpes Zoster). Deutsch. Zeitschr. f. Nerven- 
 heilk., 2G, 1 go 1. 
 
 HlLLlER, S. Epidemic poliomyelitis occurring at Stowmarket, Suffolk. 
 Brit. Med. Journ., Dec. 30, 1911. 
 
 HLAVA. Poliomyelitis ant. ac. partialiter hsemorrhagia. Quoted by Jagic, 
 Wien. med. Wochenschr., iSgg. 
 
 HOCHE. Uber spinale Kinderlahmung. Arch. f. offentliche Gesund- 
 
 heitspflege in Elsass-Lothringen, 22, 1902, S. 97. 
 -— Experimentelle Beitrage zur Pathologie des Riickenmarks. Arch. f. 
 Psychiatrie, 32. 
 
 HOCHHAUS. Uber Poliomyelitis acuta. Munch, med. Wochenschr., 46, 1909. 
 
 HOFFMANN. Cerebrale und spinale Kinderlahmung bei Geschwistern. 
 Munch, med. Wochenschr., 50, 1904. 
 
 - Zur Kenntniss der syphilitischen akuten und chronischen atrophischen 
 
 Spinallahmung. Neurol. Zentralbl., igog. 
 
 - Tiber eine Epidemie von Poliomyelitis ant. ac. in der Umgebung Heidel- 
 
 bergs im Sommer und Herbst, igo8, und bemerkenswerte Beobacht- 
 
 ungen aus friiheren Jahren. Deutsch. Zeitschr. f. Nervenheilk., 30, 
 
 Dec. 8, igog. 
 HOGYES, Lyssa. Spezielle Pathologie und Therapie von Nothnagel. 5, 
 
 AA'ien, 1897. 
 HOHMANN. Zur Behandlung des Friihstadiums der Pol. ant. ac. Munch. 
 
 med. Wochenschr., igog. 
 Holt, Emmet, and Bartlett. The epidemiology of acute poliomyelitis, 
 
 a study of thirty-rive epidemics. Amer. Journ. of Med. Sc, May, 
 
 igoS. 
 HOLT. Some clinical features of epidemic poliomyelitis. Arch, of Ped., 
 
 igio. 
 HOMEN. De Paction du streptocoque et de ses toxines sur les nerfs, les 
 
 ganglions spinaux et la moelle epiniere. Compt. rend, de la Soc. 
 
 de Biol., 3, 1896, 10 ser., p. 518. 
 HOMEN and LAITINEN. Die Wirkung einiger Bakterien und ihre Toxine auf 
 
 periphere Nerven, Spinalganglion und das Riickenmark. Zieglers 
 
 Beitr., 25, 1899. 
 HOUGH and LAFORA. Some findings in the cerebrospinal fluid in eleven 
 
 cases of acute anterior poliomyelitis, epidemic form. Fol. Neurobiol., 
 
 v, 191 1, No. 3. 
 Hounsfield. Epidemic uaralysis (polioencephalo-myelitis). Brit. Med. 
 
 Journ., Dec. 2, 1911. 
 HOWELL. A case of acute poliomyelitis in an adult. Lancet. Sep. 15, 1911. 
 HUET. Un cas de paralysie spinale infantile avec participation du nerf 
 
 recurrent. Rev. neurol., igoo. 
 HUISMANS. Uber die Pol. ant. ac. Deutsch. Arztezg., Nov. 15, 1909. 
 
 IBRAHIM and Herrmann. Uber Bauchmuskellahmung bei Pol. ant. ac. im 
 Kindesalter. Deutsch. Zeitschr f. Nervenheilk., 4905. 
 
 Immermann. Uber Pol. ant. ac. und Landrv's Paralyse. Neur. Zentralbl.. 
 1885. 
 
 Jagic. Zur Kenntniss der akuten Poliomyelitis bei Erwachsenen. Wien- 
 med. Wochenschr., 9 and 11, i8gg. 
 
LITERATURE 1 87 
 
 Jendrassic and Marie. Contribution a. l'etude de l'hemiatrophie cerebrale 
 
 par sclerose lobaire. Arch, de physiol., 3. 
 Job and Froment. Rev. de Med., Paris, igio, 30, p. 162. 
 JORG. Uber die Verkriimmungen des menschlichen Korpers und eine 
 
 rationelle Heilart derselben. Leipzig, 1810, p. 85. 
 JOEST and Degen. Untersuchungen uber die pathologische Histologic, 
 
 Pathogenese und post-mortale Diagnose der seuchhaften Gehirn- 
 
 Riickenmarkserkrankung (Bornaschen Krankheit) der Pferde. 
 
 Zeitschr. f. Hyg. u. Infect. -Krankh. der Haustiere, 9. 
 JOGICHESS. Zur Epidemiologic der Pol. ac. ant. Munch, med. Wochenschr., 
 
 1910, p. 2048. 
 Johannessen. Bemerkniger om Poliomyelitis ant. ac. Norsk. Mag. for 
 
 Laegevid., 16, p. 2gg, 1901. 
 JOHNSON and Clarke. On a remarkable case of extreme muscular atrophy, 
 
 &c. Med. Chir. Trans., 51, London, 1868. 
 JONES. Infantile paralysis as observed in health district No. 15 during 1909. 
 
 Boston, 1910, Wright and Porter Printing Co. 
 JONNESCO. Recherches cytopathologiques sur les ganglions rachidiens 
 
 dans deux cas de paralysie spinale infantile de date ancienne. Nouv. 
 
 iconogr. de la Salp., 191 1, No. 4. 
 
 Kadyi. Uber die Blutgefasse des menschlichen Ruckenmarks. Lemberg, 
 1889. 
 
 Kafka. Zerebrospinalfhissigkeit bei Poliomyelitis. Zeitschr. f. d. gesamt. 
 Neur. xiii, Heft 2. 
 
 V. Kahlden. Uber Entzundung und Atropine der Vorderhorner des Rucken- 
 marks. Zieglers Beitr., 13, p. 113, 1893. 
 
 — Neuere Arbeiten iiber Poliomyelitis anterior acuta. Zentralbl. f. allg. 
 
 Path, und path. Anatomie, 5, 1894. 
 - Uber Entzundung und Atropine der Vorderhorner des Ruckenmarks. 
 
 Verhandl. d. Kongress f. inn. Med., 1901. 
 Kaiserliches Gesundheitsamt. Ratschlage an Arzte fiir die Bekampfung 
 
 der akuten epidemischen Kinderlahmung (Poliomyelitis acuta in- 
 fantum). Berlin, 1910. 
 Kalischer. Uber Teleangiektasien mit unilateraler Hypertrophic und liber 
 
 Knochenverlangerung bei spinaler Kinderlahmung. Monatsschr. f. 
 
 Psych, u. Neurol., 1899. 
 KANDUTSCH. Einige Erfahrungen iiber Heine-Medinsche Erkrankungen im 
 
 Bezirk Deutsch-Landsberg (Steiermark). Der Amtsarzt., ii, 19 10, 
 
 No. 11. 
 Kawka. Beitrag zur pathologischen Anatomie der spinalen Kinderlahmung. 
 
 Inaug-Diss., Halle, 1889. 
 Kennedy. Recherches sur quelques formes de paralysie, qui se manifestent 
 
 chez les enfants. Arch, gener. de Med., 4 serie, 23, p. 311, 1850. 
 
 — On some of the forms of paralysis which occur in early life. Dublin 
 
 Quarterly Journal, g, 1850, and 22, 1861. 
 Kerr. The infectiousness and contagiosity of acute poliomyelitis. New 
 
 York State Journ. Med., igog. 
 KEY and RETZIUS. Studien in der Anatomie des Nervensystems und des 
 
 Bindegewebes. Stockholm, 1875-76. 
 Kling, Wernstedt, and Pettersson. Recherches sur la mode de propa- 
 gation de la paralysie infantile epidemique (maladie de Heine-Medin). 
 
 Zeitschr. f. Immunitatsforschung u. Experiment. Therapie xii, igi2. 
 Knoepfelmacher. Experimentelle Ubertragung der Pol. ant. ac. auf Affen. 
 
 Med. Klinik, 44, 1909. 
 KOPLIK. Akute Poliomyelitis (an epidemy). Arch, of Ped., May, 1909. 
 Kramer. Die spinale Kinderlahmung. Med. Klin., 52, igog. 
 Kraus. Uber das Virus der Poliomyelitis acuta, zugleich ein Beitrag zur 
 
 Frage der Schutzimpfung. "YVien. klin. Wochenschr., 7, 1910. 
 
 — Uber filtrierbares Virus iiber das Wesen der Poliomyelitis acuta. Med. 
 
 Klin., 12, igio. 
 
 — Experimentelle Beitrage zur Frage der Schutzimpfung bei Poliomyelitis 
 
 acuta. Zeitschr. f. Immunitatsforschung, 9, 2. 
 Krause, P. Zur Kenntniss der westfalischen Epidemie von akuter Kinder- 
 lahmung. Deutsche med. Wochenschr., 42, igog. 
 
 — Kurze Mitteilung iiber die rheinisch-westfalische Epidemie von akuter 
 
 Kinderlahmung. Verhandl. d. Kongress f. inn. Med., Wiesbaden, 
 igio. 
 
1 88 EPIDEMIC INFANTILE PARALYSIS 
 
 KRAUSE, P. Die akute epidemische Kinderlahmung-Therap. d. Gengen- 
 wart., iqii, Nos. 4 and 5. 
 
 KRAUSE and MEINICKE. Zur Atiologie der akuten epidemischen Kinder- 
 lahmung. Deutsche med. Wochenschr., 42, iqoq 
 
 Zur Atiologie der akuten epidemischen Kinderlahmung. II. Mit- 
 
 teilung. Deutsche med. Wochenschr., 14, iqio. 
 
 Laborde. De la paralvsie (dite essentielle) de l'enfance. These de Paris, 
 
 1864. 
 LAMY. Sur un cas d'encephalite corticale et de poliomyelite anterieure 
 
 associees. Rev. neurol., 1894. 
 
 — Sur les lesions medullaires experimentales produites par les embolies 
 
 aseptiques. Arch, de physiologie normale et pathologique, 1895 and 
 
 1897. .. 
 LANDOLT. Uber einen aussergewohnlichen Fall von Pol. ac. ant. Korre- 
 
 spondenzbl. f. Schweitz. Arzte. No. 33. 
 Landsteiner. K.k. Gesellschaft der Wiener Arzte, Dec. 18, 1908. 
 
 — Bemerkungen zu der Mitteilung von P. Krause und E. Meinicke ; Zur 
 
 Atiologie der akuten epidemischen Kinderlahmung. Deutsche med. 
 Wochenschr., 1909, p. 1975, 
 - Technik der Untersuchungen liber Poliomyelitis acuta. I Erganz- 
 ungsband des Handbuches der Technik und Methodik der Immunitats- 
 forschung. Jena, 191 1. G. Fischer. 
 
 — Diskussionsbemerkungen auf der 4 Tagung der Vereinigung fur 
 
 Mikrobiologie. Zentralbl. f. Bakt., 47. Ref. 
 Landsteiner and Levaditi. La transmission de la paralysie infantile aux 
 singes. Compt. rend. Soc. biol. a Paris, Nov. 27, 1909. 
 
 - La paralysie infantile experimentale. Ibid., Dec. 18, 1909. 
 
 La paralysie infantile experimentale. Ibid., Jan. 3, 1910. 
 
 La paralysie infantile experimentale. Ibid., Jan. 10, 1910. 
 
 - La paralysie infantile experimentale. Ibid., Feb. iq, 1910. 
 — La paralysie infantile experimentale. Ibid., March 5, 1910. 
 
 Etude experimentale de la Poliomyelite aigue (Maladie de Heine- 
 
 Medin). Ann. Pasteur, 1910, 11. 
 Landsteiner, Levaditi, and Pastia. Recherches du virus dans les organs 
 
 d'un enfant atteint de poliomyelite aigue. Acad, des sciences, June 
 
 12, 1911. 
 Landsteiner and Popper. Ubertragung der Pol. ant. ac. auf Affen. 
 
 Zeitschr. f. Immunitatsforschung, 2. 
 Landsteiner and Prasek. Ubertragung der Poliomyelitis acuta auf Affen. 
 
 II. Mitteilung. Zeitschr. fur Immunitatsforschung, 4, 1910. 
 LANGE. Zur Behandlung des Friihstadiums der Poliomyelitis. Munch. 
 
 med. Wochenschr., 49, 1909. 
 LANGER. Schule and Kinderlahmung. Jahrb. f. Kinderheilk., lxxvi, 2. 
 LANGERMANN. fiber das Vorkommen von epidemischer Kinderlahmung im 
 
 Kreise Giessen. Korrespondenzbl. d. arztl. Vereine des Grossher- 
 
 zogtums Hessen, 12, 1909. 
 Langhorst. Poliomyelitis. Journ. of Amer. Med. Assoc, Dec. 28, 1912. 
 LASCH. Zur Epidemiologic der Poliomyelitis ant. ac. Der Amtsarzt, 11, 
 
 LEAVITT. Report of some rather infrequent cases occurring in obstetric 
 
 practice. North Western Lancet, Sept., 1, 1902. 
 LEBREDO Y RECIO. Poliomyelitis anterior aguda epidemica. Epidemia de 
 
 Cuba, 1909. Sanidad y beneficiencia, 1910. 
 Leegaard. Om poliomyelit med. demonstration af mikroskopiska praparater. 
 
 Forhandl. paadet 3 norske lsegemode i Bergen, August, 1889, p. 73. 
 
 — Beretning om en epidemi of Poliomyelitis anterior acuta i Bratsberg 
 
 amt aar, 1899. Norsk. Mag. for Laegevid., 16, iyoi, p. 377. 
 
 — Etgammelt aktstykke Pol. in Norway at 1868. Norsk. Mag. for 
 
 Laegevid., Nov. 1907. 
 
 — Kliniske og epidemiologiske underscegelser over den akute poliomyelit 
 
 i Norge Videnskebs Aelskabets. Strifter Christiania, igog. 
 Leiner and v. Wiesner. Diskussionsbemerkungen zum Vortrage des 
 Herrn Zapport : Poliomyelitiserkrankungen in Wien. Gesellsch. f. 
 inn. Med. und Kinderheilk. zu. Wien. (Padiatr. Sekt.), Nov. 18. 
 igog. Berl. klin. Wochenschr., 51, igog. 
 
LITERATURE 1 89 
 
 Leiner and v. Wiesner. Experimentelle Untersuchungen iiber Poliomyelitis 
 acuta. Wien. med. Wochenschr, 42, 1910. 
 
 Experimentelle Untersuchungen iiber Poliomyelitis acuta inferior. 
 
 Wien. klin. Wochenschr., ag, igog; 3, g and 22, igio. 
 Lentz and Huntemuller. Uber akute epidemiscbe Kinderlahmung. 
 Zentralbl. f. Bakt., 47, 1910, Ref. 
 
 Experimentelle Poliomyelitis. Zeitschr. f. Hyg. u. Infekt.-Krankh., 
 
 56, 3, 1910. 
 
 — Diskussionsbemerkungen bei der Tagung d. Freien Vereinigung fur 
 Mikrobiologie. Zentrabl. f. Bakt., 47, Ref. 
 
 Leri and Wilson. Un cas de poliomyelite anterieure aigue de Fadulte avec 
 lesions medullaires en foyers. Nouv. iconogr. de la Salp, 1904. 
 
 LEVADITI and LANDSTEINER. Recherches sur la paralysie infantile experi- 
 mentale. Comptes rend. Soc. de Biol., a Paris, Jan. 3, 1910. 
 
 — Etude experimentale de la poliomyelite aigue. Ibid., lxviii, p. 417. 
 Action exercee par le thymol, le permanganate de potasse et l'eau 
 
 oxygenee sur le virus de la poliomyelite aigue. Ibid., April 30, 1910. 
 Levaditi and Stanesco. Paralysie faciale provoquee chez le singe par le 
 virus de la poliomyelite aigue. Comptes rend. Soc. de Biol., a Paris, 
 Feb. 12, iqio. 
 
 — Lesions nerveuses et atrophie musculaire chez les singes atteintes de 
 
 paralysie infantile. Ibid., April 16, 1910. 
 Levaditi. Essais de culture du rjarasite de la paralysie infantile. Presse 
 med., 1910, 6. 
 
 — L'etude experimentale de la poliomyelite aigue. Presse med., 1910, 
 
 33 and 41. 
 
 — The recent epidemiological and experimental researches on infantile 
 
 paralysis, journ. of the Royal Institute of Public Health 19, 191 1, 
 
 i-3- 
 LEWANDOWSKI. Die Heine-Medinsche Krankheit, bsw. akute Poliomyelitis. 
 
 Jahrb. f. Kinderheilk. , 73, Heft 4. 
 Leyden. Beitrage zur nathologischen Anatomie der atrophischen Lahmung 
 
 der Kinder und Erwachsenen. Arch. f. Psychiatrie, 1876. 
 
 - Uber Poliomyelitis und Neuritis. Ill Kongress f. inn. Med. Berl. klin. 
 
 Wochenschr., 20, 1884. 
 v. Leyden and Goldscheider. Spez. Pathologie und Therapie von Noth- 
 
 nagel, 10, 2. 
 V. Leyden and Redlich. Myelitis acuta. Referate. Kongress f. inn. 
 
 Med., Berlin, 1901. 
 Lhermitte. De la multiplicite des lesions et des symptomes de la soi- 
 
 disant poliomyelite anterieure aigue epidemique. Semaine med., 
 
 47, 1909. 
 LlXDER and Mally. Zur Poliomyelitisepidemie in Ober-Osterreich. Deutsche 
 
 Zeitschr. f. Nervenheilk., 38, 1910. 
 Locker. Die Poliomyelitisepidemie im osterreichischen Landbezirke Steyr. 
 
 Das osterreichische Sanitatswesen Jahrg. 21, 1909. Beilage zu No. 49, 
 
 P- 7I - 
 LOVEGREN. Bidrag till Kannedcmen om Poliomyelitis ant. ac. och nara 
 
 staende sjukdomsformer. Compt. rend. Congres Helsingfors, 1908, 
 
 p. 48. 
 
 — Zur Kenntniss der Pol. ant. ac. und subac. s. chron. Jahrb. f. Kinder- 
 
 heilk. u. psych. Erzieh, 61, 1905, H 2. 
 LOOFT and Dethloff. To tilfalde af poliomyelitis ant. ac. hos born. 
 
 Lumbalpunktion. Bakteriologisk. Untersogelse at spinalvadsken. 
 
 Medicinisk Rev., igoi. 
 LOVETT. A study of anterior poliomyelitis with analysis of 647 cases from 
 
 the Children's Hospital, Boston. Med. Record, 73, p. 1098. 
 
 — Occurrence of Infantile Paralysis in Massachusetts in 1907. Boston 
 
 Med. and Surg. Journ., July 20, 1908. 
 
 - Infantile Paralysis. Journ. of Amer. Med. Assoc, 1908, No. 20. 
 
 — The occurrence of Ant. Pol. in Massachusetts in 1907. Med. Record, 
 
 74, I9 o8 j P- 779- 
 
 — The occurrence of infantile paralysis in Massachusetts. Boston, 1910. 
 
 Wright and Porter Printing Co. 
 
 LOVETT and EMERSON. The occurrence of infantile paralysis in Massa- 
 chusetts in 1908. Boston Med. and Surg. Journ., July 12, igog. 
 
 LOVETT and Lucas. A study of 635 cases of infantile paralysis. Journ. of 
 Amer. Med. Assoc, igo8. 
 
190 EPIDEMIC INFANTILE PARALYSIS 
 
 LOW, H. B. Acute Poliomyelitis. An analysis of sixty-two cases occurring 
 
 in and around Edinburgh in the epidemic of 1910. Proc. Roy. Soc. 
 
 Med., Feb., 1912. Clin. Sec, p. 76. 
 LUCAS. The diagnosis of infantile paralysis in the prodromal and early 
 
 acute state, &c. Journ. Amer. Med. Assoc, 1908. 
 LUNDGREEN. Om den s. k. akuta barnfornlamningen i Vaxjo provinsial 
 
 lakare-distrikt ar 1905. Hygiea N.F. II. Jg. 6, 1906, p. 1089. 
 
 MACHOL. Die chirurgisch-orthopadische Behandlung der spinalen Kinder- 
 lahmung. Munch, med. Wochenschr., 1910. 
 McCLANAHAM. A brief report of the Nebraska epidemic of poliomyelitis. 
 
 Journ. of Amer. Med. Assoc, 55, 1910, 14. 
 MACKENZIE. Epidemic Poliomyelitis, with a report of ten cases. Med. 
 
 Record, 62, 1902, p. 528. 
 Macphail. A preliminary note on an epidemic of paralysis in children 
 
 Brit. Med. Journ., Dec, 1894. 
 Marburg. Zur Pathologie der Poliomyelitis acuta. Wien. klin. Rundschau, 
 
 47, 1909. 
 Marchand. Uber einen Fall von akuter Poliomyelitis bei einem Erwach- 
 
 senen. Munch, med. Wochenschr., 1910. 
 Marie, Pierre. Hemiplegie cerebrale infantile et maladies infectieuses. 
 
 Progres med., 1885. 
 — ■ Legons sur les maladies de la moelle. Paris, 1892. 
 — ■ La paraplegie cerebrale infantile. Bull, et mem. Soc. med. des 
 
 hopit., 1902. 
 
 — Sur la coincidence, chez un meme malade de la paraplegie cerebrale 
 
 infantile et de la paralyse spinale infantile. Idem., 1902. 
 Marie, Pierre and Marinesco. Sur un cas de paralysie de Landry avec 
 
 constation dans les centres nerveux de lesions poliomyelitiques liees 
 
 a la presence d'un microbe. Semaine med., 1895. 
 MARINESCO. Contribution a Tetude de la nevrite ascendante. Presse med., 
 
 1898. 
 
 — Beitrag zur Lehre von der infantilen Hemiplegie. Deutsche med. 
 
 Wochenschr., 16, 1902. 
 
 - De la transmission du virus de la poliomyelite par le nerf peripherique 
 
 et ses rapports avec les infections ascendantes. Compt. rend. Soc. 
 de Biol., a Paris, Feb. 25, 1911. 
 
 — Sur l'histologie fine de la poliomyelite experimentale. Ibid., Dec 15, 
 
 19 10. 
 
 — Transmission du virus de la poliomyelite par le sympathique. Ibid., 
 
 May 27, 191 1. 
 Marks. Infection of rabbits with the virus of poliomyelitis. Journ. of 
 
 Experiment. Med., 14. 1911, No. 2. 
 MARTIUS. Uber spinale Kinderlahmung. Arztl. Verein Rostock ref. Munch. 
 
 med. Woch., iqio, 15. 
 MATTHES. Sektionsbefund bei einer frischen spinalen Kinderlahmung. 
 
 Zeitschr. f. Nervenheilk., 13, 1898. 
 MAYER. Die Behandlung der frischen Kinderlahmung durch Ruhigstellung. 
 
 Deutsche med. Wochenschr., 24, 1911. 
 
 — Epidemic poliomyelitis. Med. Record, 79, 1911, No. 7. 
 
 MEDIN. Uber eine fipidemie von spinaler Kinderlahmung. X. Internat. 
 med. Kongr. Berlin, 1890. 
 
 - Om den infantile paralysien. Nord. med. Ark., 28, 1896, 1. 
 
 - L'etat aigu de la paralysie infantile. Arch, de med. des enf. May- 
 
 June, 1898. 
 MEINICKE. Zur Atiologie der akuten epidemischen Kinderlahmung. 
 Rheinisch-westfalische Gesellschaft ftir innere Medizin und Nerven- 
 heilk., Nov. 14, 1909. Munch, med. Wochenschr., 1, igio. 
 
 - Experimentelle Untersuchungen uber akute epidemische Kinder- 
 
 lahmung. Deutsche med. Wochenschr., 15, 1910. 
 
 - Praktische Ergebnisse der experimentellen Untersuchungen iiber akute 
 
 epidemische Kinderlahmung. Kongr. f. inn. Med., Wiesbaden, 1910. 
 MEYER, M. Die elektrizitat in ihrer Anwendung auf die praktische Medizin. 
 Second edition. Berlin, 1861, p. 207. 
 
 — Uber die Heine-Medinsche Krankheit (spinale Kinderlahmung) in der 
 
 Provinz Schleswig-Holstein in den Jahren igog-10. Arch. f. Kinder- 
 heilk., 56, 3. 
 
LITERATURE 191 
 
 MlDDLETOX. Glasgow Med. Journ., June, 1804. 
 
 MlLHIT. La paralysie soinale infantile. Progres med., 191 1, >,o. 13. 
 
 MITCHELL. Poliomyelitis in the adult. Involving all four extremities. 
 
 Journ. of Nerv. and Ment. Dis., 1903, p. 48g. 
 MODEXA. Polyneuritis and Poliomyelitis. Monatsschr. f. Psych, u. Neurol., 
 
 2g, Heft 2. 
 MOBIUS. Schmidt's Jahrbucher, 1884. 
 Moxckeberg. Anatomische Befund eines Falles von " Landryschem Sym- 
 
 ptomenkomplex.' ; ' Munch, med. Wochenschr., 45, 1903. 
 MOIR, J. H. Epidemic anterior poliomyelitis in South Derbyshire. Brit. 
 
 Med. Journ., Dec. 30, 191 1. 
 MONEY. The spinal cord of a recent and an old case of infantile palsy. 
 
 Trans. Path. Soc. of London, 35, 1884. 
 Morse. Acute poliomyeloencephalitis. Med. and Surg. Journ., 164, 1911. 
 
 — Der Wert der Lumbalpunktion und der Leukocytenzahlung bei der 
 
 Poliomyeloencephalitis. Arch, of Ped., 28, 191 1. 
 MOTT. Microscopical examination of the spinal cord, peripheral nerves 
 
 and muscles in a case of acute poliomyelitis. Arch, of Neurol., 1S99. 
 MULLER, A. Eine epidemische auftretende Erkrankung des Nervensystems 
 
 auf Nauru. Arch. f. Schiffs. u. Tropenhyg., 1910. 
 MULLER, ED. Uber die Friihstadien der spinalen Kinderlahmung. Miinch. 
 
 med. Wochenschr., 48, 1909. 
 — ■ Die spinale Kinderlahmung. Berlin, 1910, Julius Springer. 
 
 — Uber die epidemische Poliomyelitis. Arch. f. Kinderheilk., 53. 
 
 — Die serodiagnose der epidemischen Kinderlahmung. Deutsche med. 
 
 Wochenschr., 24, ign. 
 
 — Fruhstadium der Kinderlahmung. Monatsschr. f. Kinderheilk., xi, 
 
 No. 7. 
 
 — Epidemiologic der spinalen Kinderlahmung: Deutsche Zeitschr. f. 
 
 Nervenheilk., 45, Heft 3. 
 
 — Bulbare Form der epidem. Kinderlahmung. Miinch. med. Wochenschr., 
 
 4, 1912. 
 Muller, Franz. Die akute atrophische spinale Lahmung der Erwachsenen 
 (Poliomyelitis acuta anterior). Wien, i8go. 
 
 NANXESTAD. Epidemie von Poliomyelitis ant. ac. im Bezirk Hvaler im 
 Sommer 1904. Norsk. Mag. for Laegevid., No. 4. 
 
 — Beretning om en epidemi of Pol. ant. ac. i Hvaler laegedistrikt som- 
 
 meren 1904. Norsk. Mag. for Laegevid., 3 R. 4, 1906 p. 409-424. 
 Negri, quoted by Wickman. 
 NETTER. Frequence insolite des Poliomyelites en France pendant l'ete et 
 
 l'automne igog. Bull, et mem. Soc. med. des hopit., Nov. 12, ig, 26, 
 
 igog. 
 
 — Unicite vraisemblable de la poliomyelite epidemique et de la paralysie 
 
 infantile spinale. Ibid., 10, Dec. 31, igog. 
 
 — Apparation sous forme epidemique de la paralysie infantile a. Paris et 
 
 sa banlieue en igog. Bull, de FAcad. de med., May 31, 1910. 
 
 — Meningites benign.es d'allure epidemique. Bull, et mem. Soc. med. des 
 
 hopit., Oct. 21, igio. 
 
 — Paralysies infantiles a debut meningitiques. Formes meningitiques de 
 
 la maladie de Heine-Medin. Ibid., Nov. iS, 1910. 
 Netter, Gendron, and Fouraine. Serotherapie de la poliomyelite ante- 
 
 rieure aigue. Compt. rendu des seances de la Soc. de Biol., 70, 
 
 pp. 625, 707, 739. 
 Netter and Levaditi. Action microbicide exercee par le serum des malades 
 
 atteints de paralysie infantile sur le virus de la poliomyelite aigue. 
 
 Compt. rend. Soc. biol. a Paris. xApril g, igog. 
 
 — Action microbicide exercee sur le virus de la poliomyelite aigue par les 
 
 serums des sujets anterieurement atteints de paralysie infantile. 
 Ibid., Mav 21, igio. , 
 Netter and Tinel. Des modes de debut de la poliomyelite aigue et en 
 particulier de ses formes meningitiques. Association francaise de 
 pediatrie. Congres de igio. 
 
 — Poliomyelite anterieure aigue de l'adulte. Poliomyelite chez la femme 
 
 enceinte. Bull, et mem. Soc. med. des hopit., Mar. 24, ign. 
 
I9 2 EPIDEMIC INFANTILE PARALYSIS 
 
 NEURATH. Ein Fall von infantiler Hemiplegie mit poliomyelitischer Lah- 
 mung des zweiten Beines. Wien. med. Presse, igoo. 
 
 - Demonstration eines Falles von Pol. acut. AVien. med. Klub., Xov. 8, 
 
 1899, Wiener med. Presse. 
 
 - Uber seltenere Knochendeformitaten nach spinaler Kinderlahmung. 
 
 AVien. med. Presse, igoi. 
 Xeurath. Beitrage zur Anatomie der Pol. ant. ac. Arb. a. d. Neurol. Instit. 
 a. d. AViener Univers., 12, p. 297, 1905. 
 
 — Klinische Studien iiber Pol. II. Klinische VJntersuchung an 240 Fallen 
 
 von spinalen Kinderlahmung. Jahrb. f. Kinderheilk., 61, Heft 5, 1905, 
 p. 742. 
 
 — Atypische Poliomyelitisfalle. AA^ien. klin. AA'ochenschr. , 1909. 
 
 — Erfahrungen wahrend der Poliomyelitisepidemie 1908-09 in Wien. 
 
 Wien klin. AVochenschr., 22 and 37, 1909. 
 Xeustadter. Acute Poliomyelitis. Journ. of Amer. Med. Assoc, Sept. 7, 
 
 1912. 
 Xeustadter and Thro. Experimental poliomyelitis produced in monkeys 
 
 from the dust of the sick-room. Proc. of the New York Path. Soc, 9, 
 
 191 1, Nos. 3 and 4. 
 Xew York Report on the epidemic of 1907. 
 
 Xewmark. A little epidemic of poliomyelitis. The Med. News, 1899. 
 Xiedxer. Ein Fall von Poliomyelitis acuta der Erwachsenen. Munch. 
 
 med. AA r ochenschr., 18, 1898. 
 NIEMANN. Poliomyelitis acuta. Charite ann., xxxvi. 
 XOBECOURT and Darre. Reactions meningees anatomiques et cliniques a la 
 
 suite de l'injection intraxachidienne du serum humain dans un cas de 
 
 maladie de Heine-Medin. Compt. rend. Soc. biol. a Paris, 69. 
 XONNE. Riickensmarkerkrankungen in Fallen von pernicioser Anamie, von 
 
 Sepsis und von Senium, usw. Deutsche Zeitschr. f. Xervenheilk., 14, 
 
 1899. 
 
 Oettinger and Marinesco. De l'origine infectueuse de la paralysie 
 ascendente aigue ou maladie de Landry. Semaine med., 1895^ 
 
 Oppenheim. Uber die Poliomyelitis anterior chronica. Arch. f. Psvchiatrie, 
 19, 1888, p. 381. 
 
 — Zur Pathologie der chronischen atrophischen Spinallahmung. Arch. f. 
 
 Psychiatrie, 24, 1892. 
 
 — Zur Encephalitis pontis des Kindesalters, zugleich ein Beitrag zur 
 
 Symptomatologie der Facialis- und Hypoglossus-lahmung. Berl. 
 klin. AVochenschr., 1899. 
 — ■ Lehrbuch der Nervenkrankheiten, 1908. 
 
 OSGOOD and LUCAS. Transmission experiments with the virus of polio- 
 myelitis. Journ. of Amer. Med. Assoc, 56, 1911, No. 7. 
 
 Oulment and BAUDOUIN. Poliomyelite anterieure a. rechute. Role possible 
 d'un traumatisme anterieur. Rev. neurologique, 191 1, No. 6. 
 
 Oxholm. Tilfaelde af omtrent samtidig optraedente Lammelse hos Born. 
 Tidskrift. f. prakt. Med., 1887. 
 
 Packard. Acute anterior poliomyelitis occurring simultaneously in a 
 brother and sister. Journ. of Nerv. and Mental Dis., 1899. 
 
 Painter. An epidemic of infantile paralysis. Boston Med. Journ., Dec. 11, 
 1902. 
 
 Parker. An epidemic of infantile paralysis in Bristol. Brit. Med. Journ., 
 Mar. iS, 1911. 
 
 Parrot and Joffroy. Note sur un cas de paralysie infantile. Arch, de 
 physiol. norm, et path., 3, 1870, p. 309. 
 
 PASTEUR. An epidemic of infantile paralysis occurring in children of the 
 same family. Trans, of Clin. Soc, 30, London, 1897. 
 
 Pasteur, Foulerton, and MACCORMAC. Etiology of acute poliomyelitis. 
 Lancet, 1908. 
 
 Paul. The treatment of acute poliomyelitis. Med. and Surg. Journ., 164, 
 191 1. 
 
 Peabody, Draper, and Dochez. Acute Poliomyelitis. Monogr. Rocke- 
 feller Inst., No. 4. 
 
 Peiper. Das Auftreten der spinalen Kinderlahmung (Heine-Medinsche 
 Krankheit) in Vorpommern. Deutsche med. AA r ochenschr. , g, igio. 
 
LITERATURE 193 
 
 Perkins and Dudgeon. A case of acute poliomyelitis in an adult with 
 
 marked bulbar and ocular symptoms. Microscopical report. Brain, 
 
 117, 1907. 
 Petit fils. Considerations sur Fatrophique aigue des cellules motrices. 
 
 Paris, 1873. 
 PETREN. Till fragen om poliomyelitis kliniska srallning, dess prognos 
 
 och therapi. Nord. Tidskr. f. Therapi, 1909. 
 Petren and Ehrenberg. Etudes cliniques sur la poliomyelite aigue. Nouv. 
 
 iconogr. de la Salp., 1909. 
 PETTERSEN. Epidemisk. poliomyelit i Lier, iqo6. Tidskrift f. d. norske 
 
 laegeforening, 1908, pp. 393, 444. 
 PlERRACINI. Una epidemia di paralisi atrophica spinale infantile. Lo 
 
 Speriment, 1895. 
 PlOTROWSKA. Contribution a l'etude anatomique de la paralysie infantile. 
 
 These de Paris, 191 1. 
 PlRlE, J. Harvey. A case of rapidly fatal acute poliomyelitis in an adult. 
 
 Rev. of Neurol, and Psychiat., Edinburgh, 1910. 
 PLACZEK. Beitrag zur spinalen Kinderlahmung. Berl. med. Gesellsch., 
 
 May 8, 1901 ; Deutsche med. Wochenschr., 21, 1901. 
 
 — Zur pathologischen Anatomie der spinalen Kinderlahmung. Berl. klin. 
 
 Wochenschr., 44, igoi. 
 PLATOU. Nogle oplysninger om en epidemi af pol. ant. ac. i Aafjorden 
 
 hosten, 1904. Tidskrift f. d. norske laegeforening, 1905. 
 PleuSS. liber gehauttes Vorkommen spinaler Kinderlahmung. Diss., 
 
 Kiel, 1899. 
 POTPESCHXIGG. Bakteriologische Untersuchungsergebnisse bei Poliomyelitis 
 
 (Heine-Medinsche KrankheitJ. Wien. klin. Wochenschr., 30, 1909- 
 
 — Beobachtungen und Untersuchungsergebnisse aus der steiermarkischen 
 
 Poliomyelitisepidemie im Jahre 1909. Arch. f. Kinderheilk., 54, 
 
 1910. 
 Praetoritjs. Zur pathologischen anatomie der Poliomyelitis ant. ac. infant. 
 
 Jahrb. f. Kinderheilk., 58, 1903; supplement to Heft 1. 
 Prevost and Vulpian. Observation de paralysie infantile. Compt. rend. 
 
 de la Soc. de Biol., Dec, 1865. 
 PROBST, Uber die Folgen der soinalen Kinderlahmung auf die hoher 
 
 gelegenen Nervenzentren. Wien. klin. Wochenschr., 1898. 
 Proscher. Zit nach Fox. 
 Purckhammer. Zur Frage der poliomyelitischen Lahmungen. Miinch. 
 
 med. Wochenschr., 22, 191 1. 
 PUSCHNIG. Die poliomyelitisepidemie des Jahres 1909-10 in Karnten. Das 
 
 oesterreich. Sanitatswesen, 191 1, 12 and 16. 
 
 RANCKEX. Nagra fall af " barnforiamning " behandlade med. " banande 
 ofningsterapi." Finska Lakarasellsk. Handl., 1909. 
 
 RAUZIER. La reviviscence des poliomyelitis. Journ. de med. int., 191 1, 
 No. 12. 
 
 Raymond. Paralysie infantile. Atrophie musculaire. Compt. rend, de la 
 Soc. de Biol., 1S75. 
 
 — La paralysie ascendante aigue dans ses rapports avec la poliomyelite 
 
 anterieure et la Dolynevrite motrice. Lecons sur les maladies du 
 
 systeme nerveux. Paris, 1897. 
 Raymond and Sicard. Meningite cerebrale spinale a forme de paralysie 
 
 infantile, cytodiagnostic. Rev. neurol., 1902. 
 Reckzeh. Die akute spinale Kinderlahmung im rheinisch-westfalischen 
 
 Industrie-bezirk. Med. Klin., 45, 1909. 
 REDLICH. Beitrag zur pathologischen Anatomie der Pol. ant. ac. infant. 
 
 Wien. klin. Wochenschr., 1894. 
 REECE. Certain aetiological considerations arising from observations of the 
 
 behaviour of poliomyelitis in Devon and Cornwall, 1911. Proc. Roy. 
 
 Soc. Med. (Epidem. Sec), Feb., 1912. Report to L.G.B. on Public 
 
 Health, New Series, No. 61, 1912. 
 Renault. Une epidemie de poliomyelite dans la Creuse. Soc. med. des 
 
 hopit., Mar. 24, 1911. 
 Renault and Martingay. Poliomyelite aigue chez une femme enceinte. 
 
 Soc med. des hopit., Mar. 24, iqii. 
 V. REUSS. Ein Fall von Paralvsis ascendens Landrv. Char. Ann., 23, 
 
 1898. 
 
 13 
 
194 EPIDEMIC INFANTILE PARALYSIS 
 
 Rilliet and Barthez. Traite des maladies des enfants. 2, Paris, 1843, 
 
 P- 335- 
 — ■ — Traite des maladies des enfants. Second edition, Paris, 1861. 
 Rissler. Zur Kenntniss der Veranderungen des Nervensystems bei Polio- 
 myelitis ant. ac. Nord. med. Ark., 20, 1888. 
 
 — Quoted by v. Kahlden. Zentralbl. f. allg. Path, und path. Anat. , 5, 
 
 1804. 
 Robertson and Chesley. Pathology and Bacteriology of acute anterior 
 
 poliomyelitis. Journ. of Arner. Assoc, 55, igio. 
 ROCAS and Carles. Paralvsie infantile des muscles de la paroi abdominale 
 
 avec pseudohernie ventraie. Arch, de med. des enf., 1908. 
 ROGER. Atropine musculaire progressive experimentale. Ann. Pasteur, 
 
 1892. 
 Roger and Damaschino. Recherches anatomo-pathologiques sur la 
 
 paralysie spinale de l'enfance. Compt. rend, de la Soc. de Biol., 3, 
 
 1871. 
 Des alterations de la moelle epiniere dans la paralysie spinale de 
 
 l'enfance et dans l'atrophie musculaire progressive. Rev. de med., 
 
 18S1. 
 ROMER. Diskussionsbemerkungen 1m arztlichen Verein zu Marburg, Nov. 3, 
 
 igog. Munch, med. AA'ochenschr., 48, igog. 
 
 — Untersuchungen zur Atiologie der epidemischen Kinderlahmung. 
 
 Miinch. med. AVochenschr., 49, igog. 
 
 — Diskussionsbemerkungen gelegentlich der XIII Versammlung siidwest- 
 
 deutsche Kinderarzte in Frankfurt a. Main. Arch f. Kinderheilk., 53. 
 
 — Weitere Mitteilungen liber experimentelle Affen-Poliomyelitis. Miinch. 
 
 med. Wochenschr. , 5, igio. 
 
 — Diskussionsbemerkungen gelegentlich der 4 Tagung der Freien 
 
 Vereinigung fiir Mikrobiologic, Berlin, May 20, igio. Zentralbl. f. 
 Bakt., 47, Ref. 
 
 — Epidemiologische und atiologische Studien iiber die spinale Kinder- 
 
 lahmung. Verhandl. des Deutschen Kongresses f. inn. Med., Wies- 
 baden, 1910. 
 
 — Nachlese aus der experimentellen Erforschung der Poliomyelitis acuta. 
 
 Med. Kim., 28, 1911. 
 
 — Uber eine durch filtrierbares virus bedingte Meerschweinchenkrankung. 
 
 Zentralbl. f. Bakt., 50, Ref. 
 
 — tiber eine der Kinderlahmung des Menschen sehr ahnliche Erkrankung 
 
 des Meerschweins. Deutsche med. Wochenschr., 26, 191 1. 
 
 — Uber den Erreger der Meerschweinchenlahme. Sitzungsber. der 
 
 Gesellsch. z. Beford. d. gesamt. Naturwissench. Marburg, 3, ign. 
 
 — Experimentelle Poliomyelitis. Ergebn. d. inn. Med. u. Kinderheilk.. 
 
 1912. 
 ROMER and JOSEPH. Beitrag zur Natur des Virus der Epidemischen Kinder- 
 lahmung. Miinch. med. AVochenschr., 7, igio. 
 Uber Immunitat und Immunisierung gegen das Virus der epidemi- 
 schen Kinderlahmung. Ibid., 10, igio. 
 
 Spezifisch wirksames Serum gegen das Virus der epidemischen 
 
 Kinderlahmung. Ibid., 11, igio. 
 
 Beitrage zur Prophylaxe der epidemischen Kinderlahmung. Ibid., 
 
 iS, 1910. 
 
 Zur Natur und Verbreitungsweise des Poliomyelitisvirus. Ibid., 20, 
 
 igio. 
 
 Noch einige Experimente zur Poliomyelitisfrage. Ibid., 51, igio. 
 
 Rosenau, Sheppard, and ARROSS. Poliomyelitis anterior. Boston Med. 
 
 and Surg. Journ., May 25, 191 1. 
 ROSET, J. Pequeha epidemia de poliomyelitis anterior aguda infantil. 
 
 Med. de los ninos, igos, No. 4. 
 ROSSI. Reprises chroniques de poliomyelite aigue de l'enfance avec 
 apparences de myopathic Rev. neurol., igo5. 
 
 — Coincidence chez un meme malade de la paraplegie cerebrale infantile 
 
 et de la paralvsie spinale infantile. Nouv. iconogr. de la Salp., igo7. 
 ROTH. Anatomischer Befund bei spinaler Kinderlahmung. Virchow's 
 
 Arch., 58, 1873. 
 ROTHMAXW tiber die sckundaren Degenerationen nach Ausschaltung des 
 
 Sakral- und Lendenmarkgrau durch Riickenmarksembolie beim Hunde. 
 
 Arch, f Anat. u. Phvsiol., iSgg. 
 
LITERATURE 1 95 
 
 RUMPF. Beitrage zur pathologischen Anatomie des zentralen Xerven- 
 systems. Arch. f. Psych., 1885. 
 
 Russell, J. RISIEX. The prognosis and treatment of acute anterior polio- 
 myelitis. Med. Soc. Trans., 1908. 
 
 Sahli. Zur Lehre von den spinalen Lokalisationen. Deutsch. Arch. f. klin. 
 
 Med., 1883. 
 SALOMON". Zur Diagnose u. Therapie einiger Lahmungsformen im kind- 
 lichen Alter. Jahrb. f. Kinderheilk., N.F. 1, 1868. 
 SANDER. liber Riickwirkung der spinalen Kinderlahmung auf die 
 
 motorischen Gebieten der Hirnrinde. Zentralbl. f. d. med. Wis- 
 
 sensch., 1875. 
 Saunders, P. W. Poliomyelitis with extensor response. Proc. Roy. Soc. 
 
 Med. (Xeurol. Sec, p. 75), 1912. 
 SCHAFFER. Pathologie u. pathol. Anatomie der Lyssa. Zieglers Beitrage 
 
 z. Path. u. path. Anat., 7, 1890. 
 SCHAUB, G. Zur Pathologie der epidemischen Kinderlahmung. Deutsch. 
 
 Zeitschr. f. Xervenheilk., 43, 191 1, 1 and 2. 
 Scheltema, Maxshot, Travagliaxo, &c. Medeeling over de poliomyelitis- 
 
 opeentooping, 1905-06 in Xederland. Xed. Tydschr. von Geneesk, 33, 
 
 777- 
 Schlesixger. Verhandl. der deutschen Xervenaxzte. Ill Jahresversamm- 
 
 lung, Wien, 1909. 
 SCHMAUS. Beitrag zur Kasuistik der akuten haemorrhagischen Myelitis, 
 Myelitis bulbi und Landryschen Paralyse. Zieglers Beitrage z. Path, 
 u. path. Anat., 1905. 
 
 — Akute Myelitis. Ergebnisse von Lubarsch-Ostertag. Wiesbaden, 1904. 
 SCHMAUS and SACKI. Vorles. uber die path. Anat. d. Riickenmarks., 1901. 
 SCHOXKA. Uber die x-\rt des Auftretens der infectiosen Poliomyelitis. Das 
 
 osterreich. Sanitatswesen. Jahrg. xxi, 1909, 49, p. 498. 
 SchOTTMUller. Positive Wassermann reaction in the blood of four cases 
 
 anterior poliomyelitis; not in cerebrospinal fluid. Arztliche Verein in 
 
 Hamburg, June 25, 1912. 
 Schreiber. La poliomvelite epidemique, Maladie de Heine-Medin. Paris, 
 
 191 1. G. Steinheil. 
 Schroder. Die im Tettower Kreise in letzter Zeit festgestellten Falle von 
 
 spinaler Kinderlahmung. Zeitschr. f. Medizinalbeamte, 3, 191 1. 
 SCHULLER. Drei Falle ooiiomyelitischer Lahmung einer unteren Extremitat 
 
 mit positivem Babinski. X~eurol. Zentralbl., 1905. 
 Schultze. Beitrage zur Patholoeie und pathologischer Anatomie des 
 
 zentralen Xervensystems, insbesondere des Ruckenmarks. Virchow's 
 
 Arch., 68, 1876. 
 
 — Die anatomischen Veranderungen bei den akuten atrophischen Lah- 
 
 mungen der Erwachsenen. Ibid., 73, 1878. 
 
 — Befund bei spinaler Kinderlahmung nach dreijahrigem Bestehen 
 
 derselben. Xeurol. Zentralbl., 19, 1882. 
 
 — Tiber die Ursache der akuten Poliomyelitis. Xiederrhein. Gesellsch. f. 
 
 Xatur- und Heilkunde in Bonn, Xov. 22, 1897. Deutsche med. 
 Wochenschr., 5, 1897, 25. 
 
 — Zur Atiologie der akuten Poliomyelitis. Munch, med. Wochenschr., 
 
 38, 1S98. 
 
 — Zur Anatomie und Atiologie der akuten Poliomyelitis. Munch, med. 
 
 Wochenschr., 23, 1904 (Sitzungsbericht). 
 
 — Zur pathol. Anatomie und Atiologie der akuten Poliomyelitis. Zieglers 
 
 Beitrage z. Path. u. path. Anat., 7, 1905. 
 SCHWALBE. Untersuchung eines Falles von Poliomyelitis acuta infantum 
 
 im Stadium der Reparation. Zieglers Beitrage z. Path. u. path. Anat., 
 
 32, 1Q02. 
 Schwartz. Petersburger med. Wochenschr., 1909. 
 Seeligmuller. Uber Lahmungen im Kindesalter. Jahrb. f. Kinderheilk., 
 
 X. F. 12, 1878-79. 
 
 — Spinale Kinderlahmung. Handbuch d. Kinderkrankh., herausgeg. von 
 
 Gerhardt, 5, 1880. 
 SELEXSKY. Zur Frage der Heine-Medinsche Krankheit. Russkij Wratsch., 
 
 39, !QJo. 
 
 Seller. Diskussionsbemerkungen auf der 4 Tagung der Vereimgung f. 
 Mikrobiologie. Zentralbl. f. Bakt., 47. 
 
196 EPIDEMIC INFANTILE PARALYSIS 
 
 SHERMAN and SPILLER. Acute polioencephalomyelitis in an adult. Phila. 
 
 Med. Journ., igoo. 
 Shidler. The epidemic of spinal disease in Nebraska. Journ. of Amer. 
 
 Med. Assoc, 1910. 
 SlEMERLING. Zur pathologischen Anatomie der spinalen Kinderlahmung. 
 
 Arch. f. Psychiatrie, 26, 1894. 
 
 — Neurol. Zentralbl., 10, 1891. 
 
 SINGER. Uber experimentelle Embolien im zentralen Nervensystem. 
 
 Zeitschr. f. Heilk., 18, 1907. 
 Sitta. Autopsie d'un cas de paralysie infantile. XIII. Internat. Med. 
 
 Congress, Paris, 1900. 
 Sneve and Ramsey. Epidemic poliomyelitis. St. Paul Med. Journ.. 
 
 1 1, 1909. 
 SOLTAU. Acute Poliomyelitis. Brit. Med. Journ., Nov. 4, 191 1. 
 Spieler. Zur Epidemie der Heine-Medinsche Krankheit (Pol. ant. ac.) in 
 
 AVien, 1908-09. AVien. med. AYochenschr. , 13, 1910. 
 SPILLER. A report of two cases of paraplegia occurring in variola, one 
 
 being a case of anterior poliomyelitis in an adult. Brain, 103, 1903. 
 STADELMANN. Beitrag zur Path und. path. Anatomie der Ruckenmarks- 
 
 erkrankungen. Deutsch. Arch. f. klin. Med., 33, 1883. 
 V. STARCK. Gehauftes Vorkommen spinaler Kinderlahmung. Miinch. med. 
 
 AA r ochenschr. , 34, 1910. 
 
 — Med. klinik., No. 51. 
 
 Starr. Epidemic infantile paralysis. Journ. of Amer. Med. Assoc, 51, 
 1908. 
 
 — The prevention of epidemics of infantile paralysis. Med. Record, 
 
 Aug. 5, 1911. 
 
 — Acute Poliomyelitis ; in the Svstem of Medicine. Edited by Allbutt and 
 
 Rolleston, second edition, vol. vii, 1910. 
 STEIN, R. A case of abortive poliomyelitis. Med. Record, July 15, 191 1. 
 STEPHENS. Recent epidemics of 135 cases of acute anterior poliomyelitis 
 
 occurring in Victoria. Intercolonial Med. Journ. of Australasia, 1908. 
 STERN, R. Klinische Studien iiber die Zukunft nervenkranker Kinder mit 
 
 spinalen u. zerebralen Lahmung. Jahrb. f. Psych, u. Neurol., 32, 
 
 p. 139, 1911. 
 Sterne. Rapports de la paralysie infantile avec la paralysie spinale aigue 
 
 de l'adulte et Fatrophie musculaire progressive. These de Nancy, 
 
 1891. 
 STIEFLER. Uber die epidemische spinale Kinderlahmung und ihr Auftreten 
 
 in Oberosterreich. Med. klinik., 44, 1910. 
 Strassburger. Zur Klinik der Bauchmuskellahmung auf Grund eines 
 
 Falles von isolierter partieller Lahmung nach Pol. ant. ac. Deutsche 
 
 Zeitschr. f. Nervenheilk., 1906. 
 Strauss. The pathology of acute poliomyelitis. Report of the collective 
 
 investigation committee on the New York epidemic of 1907. 
 
 — The -nathology of acute poliomyelitis. Pediatrics, Aug., 1910. 
 
 — Inoculation of nasal secretion from patients with acute poliomyelitis. 
 
 Journ. of Amer. Med. Assoc, April 22, 191 1. 
 STRAUSS and HUNTOON. Experimental studies on the aetiology of acute 
 
 poliomyelitis. New York Med. Journ., Jan., iqio. 
 Strobel, Fricke and Dahm. Die spinale Kinderlahmung. Duisburger 
 
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 STRUMPELL. Uber die Ursachen der Erkrankungen des Nervensystems. 
 
 Deutsch. Arch. f. klin. Med., 35, 18S4. 
 
 — Uber akute Encephalitis der Kinder (Polioencephalitis acuta, cerebrale 
 
 Kinderlahmung). Jahrb. f. Kinderheilk., 1S85. 
 
 — Zur Atiologie der spinalen Kinderlahmung (Poliomyelitis acuta). 
 
 Beitrag. z. path. Anat. u. klin. Med., Leipzig, 1887. 
 
 — Storungen der Sensibilitat bei Poliomyelitis. Deutsch. Zeitschr. f. 
 
 Nervenheilk., 45, 2. 
 
 — Akute Poliomvelitis. Deutsche med. AArochenschr., 1908, p. 1611, 
 
 Vereinsbeilage. 
 Strumpell and Barthelmes. Uber Pol. ac der Erwachsenen und iiber das 
 
 Verhaltniss der Poliomyelitis zur Polyenuritis. Deutsch. Zeitschr. 
 
 f. Nervenheilk., 18, 1900. 
 Sturm. Spinale Kinderlahmung und epidemische Parese bei Hunden. 
 
 Berl. tierarzl. AVochenschr., 47, p. S67, 1909. 
 
LITERATURE 1 97 
 
 TAKAHASHI. Ein Fall akut entstandener doppelseitiger Lahmung des 
 
 ausseren Oculomotorius und des Trochlearis. Klin. Monatsblatter 
 
 fiir Augenheilkunde, iqo8. 
 Tayler, H. L. Is infantile paralysis epidemic? New York Med. Journ., 
 
 Aug. 7, 1897. 
 Taylor, E. W. Poliomyelitis of the adult. Journ. of Ment. and Nerv. Dis., 
 
 Aug., 1902. 
 Taylor, Fred. Transactions of Path. Soc. London, 30, p. 197, 1879. 
 
 — Guy's Hosp. Reports, 52, 57, 1895. 
 
 Taylor, M. An epidemic of poliomyelitis. Phila. Med. Journ., Jan. 29, 
 
 1898. 
 Tedeschi. Paralisi spinale infantile acuta con emiatrofia faciale ed atrofia 
 
 del nervo ottico. Atti dell' Accademia di Sc. Med. e Natur. in 
 
 Ferrara, 1904. 
 Thoinot and Masselin. Contributions a l'etude des localisations medullaires 
 
 dans les maladies infectieuses. Deux maladies experimentales a type 
 
 spinal. Rev. de med., 1894, p. 449. 
 THOMAS. Two cases of acute ascending paralysis with autopsies. Journ. 
 
 of Nerv. and Ment. Dis., 1897. 
 Thomsen, O. Experimentelle Untersuchungen fiber Poliomyelitis. Berl. 
 
 klin. Wochenschr., No. 2, 1912. 
 Thomson. Acute poliomyelitis. Med. Record, Aug. 10, 1912. 
 TIEDEMANN. Poliomyelitis acuta und Meningitis cerebrospinalis. Munch. 
 
 med. Wochenschr., 19.06. 
 Tomkyns. Acute anterior poliomyelitis in S. Staffordshire. Brit. Med. 
 
 Journ., Jan. 27, 1912. 
 Treves. Brain, 32, p. 285, 1909. 
 Triboulet and Lippmann. Poliomyelite anterieure aigue, ponction lombaire, 
 
 mononucleose. Bull, et mem. Soc. med. des hopit. de Paris, igo2. 
 Turner. A portion of the spinal cord, with drawings and microscopical 
 
 specimens, from a case of acute anterior poliomyelitis in a child, 
 
 fatal within six weeks from the onset. Trans. Path. Soc, London, 
 
 30, 1879. 
 TWOST. Etude de quelques microbes pathogenes au point de vue de la 
 
 genese de la poliomyelite aigue. Compt. rend. Soc. biol. a Paris, 70, 
 
 1911. 
 
 Underwood. A treatise on the disorders of childhood and the management 
 of infants from the birth. Third edition. London, 2, p. 87, 1814. 
 
 — Traite des maladies des enfants. Trad, de Tanglais par Lefebre de 
 
 Villebrune, Paris, 1786. 
 
 — Traite des maladies des enfants. Trad, de l'anglais par Eusebe de 
 
 Salle. Paris et Montpelier, p. 674, 1823. 
 
 — Handbuch der Kinderkrankheiten. Von Dr. F. W. Schulte, 1S48. 
 
 VlETEN. Die akute spinale Kinderlahmung als epidemische Infektions- 
 
 krankheit. Zeitschr. f. arztl. Fortbildung 20, p. 634, 1909. 
 VINCENT. Sur un cas experimental de poliomyelite infectieuse aigue ayant 
 
 simule le syndrome de Landry. Arch. med. Exper., 1893. 
 VlPOND. Etiology of Poliomyelitis. Brit. Med. Journ., March, 18, igu. 
 VOLKMANN. fiber Kinderlahmung und paralytische Contracturen. Samm- 
 
 lung klin. Vortrage, 1, 1870. 
 VULPIAN. Cas d'atrophie muse, graisseuse, &c. Arch, de phys. norm, et 
 
 pathol., 3, 1868. 
 Vulpius. Die Behandlung der spinalen Kinderlahmung. Leipzig, 1910. 
 
 Wade, R. R. The recent epidemic of infantile paralysis. Australasian 
 
 Med. Gaz., July, 1904. 
 Walcher. Die Zerebrospinal-Meningitis. Epidemie in Lommis (Kanton 
 
 Thurgau) im Sommer igoi. Korrespondenzbl. f. Schweiz Arzte., 
 
 1906. 
 Walter. Epidemische Kinderlahmung und Trauma. Monatsschr. f. 
 
 Unfaltheilk. u. Invalidenrer, 18 Jahrg., No. 8. 
 
 — Histopathologic der Akuten Poliomyelitis. Deutsch. Zeitschr. f. 
 
 Nervenheilk, 45, 2. 
 Wendenburg. Pol. ant. ac. Statistik der in der Gottinger medizinischen 
 Klinik u. Poliklinik von 1874 bis 1901 beobachteten Falle von Polio- 
 myelitis. Inaug.-Diss., Gottingen, 1903. 
 
ig8 EPIDEMIC INFANTILE PARALYSIS 
 
 WEST. Lectures on the diseases of infancy and childhood. Second edition. 
 
 London, 1852, p. 145. 
 WESTERMANN. Die in der Gottinger medizinischen Poliklinik vom Jan. 1, 
 
 1877, bis Jan. 1, 1901, beobachteten Falle von Pol. ant. ac. Inaug. 
 
 Diss. 3 Gottingen, 1903. 
 WlCKMAN. Studien zur Poliomyelitis acuta. Zugleich ein Beitrag zur 
 
 Kenntniss der Myelitis ac. Arb. aus d. path. Institut d. Universitat 
 
 Helsingfors, 1905, p. 109. 
 
 — Studien iiber Poliomyelitis acuta. Berlin, 1905. 
 
 — Beitrage zur Kenntniss der Heine-Medinsche Krankheit (Pol. ac. 
 
 und verwandte Erkrankungen). Berlin, 1907. 
 
 — Uber die Prognose der ak. Pol. und atiol. verwandte Erkrankungen. 
 
 Zeitschr. f. klin. Med., 63, Heft 1 to 4, p. 362. 
 
 — Sur les pretendues relations entre la poliomyelite ant. aigue et la 
 
 meningite cerebrospinale sous forme epidemique. Mem. de la Soc. 
 med. des hopit. de Paris. 
 
 — Weitere Studien iiber Pol. ac. Ein Beitrag zur Kenntniss der Neurono- 
 
 phagen und Kornchenzellen. Deutsche Zeitschr. f. Nervenheilk., 38. 
 
 — Uber akute Poliomyelitis und Polyneuritis. Zeitschr. f. die gesammte 
 
 Neurol, u. Psych., 4, 1910, Heft 1. 
 — ■ Verhandl. der 82 Versammlung Deutscher Naturforscher und Arzte. 
 Kbnigsberg, 1910. 
 
 — Die akute Poliomyelitis resp. Heine-Medinsche Krankheit. Berlin, 191 1. 
 WILEY and DARDEN. An epidemic of acute anterior poliomyelitis. Journ. 
 
 of Amer. Med. Assoc, 52, 8, 1909. 
 
 WlEKE. Ercheinungen der Poliomyelitis ant. ac. (spinale Kinderlahmung 
 bei Hiihnern). Deutsche tierarztl. Wochenschr., 16, 1909. 
 
 Williams. A case of Striimpells paralysis (Polioencephalitis) combined 
 with infantile paralysis. Lancet, 1898. 
 
 WILLIAMSON. The early changes in the spinal cord in acute anterior polio- 
 myelitis of the adult. Med. Chronicle, 1890. 
 
 WlTTEK. Zur Behandlung der postpoliomyelitischen schlaffen Lahmung. 
 Wien. klin. Wochenschr., 4, 1910. 
 
 WOHLGEMUTH and SZECSI. Zerebrospinal flussigkeit in Pol. ant. ac. 
 Zeitschr. f. die gesammte. Neurol., 13, 3 and 4. 
 
 WOLLENWEBER. Beobachtungen iiber die epidemisch auftretende Spinale 
 Kinderlahmung. Zeitschr. f. Medizinalbeamte, 21, 1909. 
 
 WOLLSTEIN. A biological studv of the cerebrospinal fluid in anterior Polio- 
 myelitis. Journ. of Experiment. Med., 1908. 
 
 Zappert. Klinische Studien iiber Poliomyelitis. Jahrb. f. Kinderheilk., 
 N. F., 3, Heft 2, 1901. 
 
 — Uber gehauftes Auftreten und Gelegenheitsursache der Poliomyelitis. 
 
 Jahrb. f. Kinderheilk., 53. 
 — ■ Bemerkungen iiber die derzeitigen Poliomyelitis-epidemie in Wien und 
 Umgebung. Wien. klin. Wochenschr., 47, 1908. 
 
 — Die Poliomyelitiserkrankungen in Wien und Nieder-Osterreich _ im 
 
 Jahre 1908. Gesellsch. f. inn. Med. und Kinderheilk. in Wien, 
 Nov. 4, 1909. Berl. klin. Wochenschr., 47, 1909. 
 
 — Die epidemie der Heine-Medinschen Krankheit (Poliomyelitis) in Wien 
 
 und' Nieder-Osterreich im Jahre 1908. AVien. med. Wochenschr., 
 46, 1909. Jahrb. f. Kinderheilk., 72, 1910. 
 
 — Organische Erkrankungen des Nervensystems. Handb. der Kinder- 
 
 heilk. von Pfaundler und Schlossmann. Second edition, iqio. 
 
 — Verhandlungen der 82 Versammlung Deutscher Naturforscher und 
 
 Arzte. Konigsberg, 10 10. 
 Zappert, Leiner and v. Wiesner. Studien iiber die Heine-Medinsche 
 Krankheit (Poliomyelitis acuta). Liepzig u. Wien, 191 1. 
 
Ind 
 
 ex. 
 
 ADULTS, infantile paralysis in, 10 
 
 — , prognosis of Heine-Medin disease bad in, 20 
 
 Alimentary tract, complications in prodromal stage of Heine-Medin 
 
 disease, 14 
 
 , entrance of poliomyelitis virus by, 101 
 
 America, North, epidemics of Heine-Medin disease in, 140 
 
 Analgesia in Heine-Medin disease, 16 
 
 Andre, cases of infantile paralysis in France, 140 
 
 Animals, durability of poliomyelitis virus in, 67, 68 
 
 Antibodies in serum from cases of Heine-Medin disease, 168-170 
 
 — ■ — from experimental poliomyelitis, successful demonstration, 163-166 
 
 — , virus and serum containing, immunization with, 160 
 
 Antiformin extracts in testing reaction in fixation of complement, 163 
 
 Artery, anterior spinal, 131 
 
 , embolism in Heine-Medin disease, reason for rejection of 
 
 theory, 131, 132 • 
 
 Auerbach, epidemic of infantile paralysis in Germany, 138 
 Australia, epidemics of Heine-Medin disease in, 141 
 Austria, epidemic of Heine-Medin disease in, 138 
 
 BACILLUS COLI, intravenous infection in rabbits producing paralysis, 30 
 Bacteriological research in Heine-Medin disease, 26 
 
 , negative, 27 
 
 Badham, case of infantile paralysis, 6 
 
 Batten, F. E., cases of infantile paralysis, 13Q 
 
 Beclere, cases of infantile paralysis in France, 140 
 
 Bergenholtz, epidemic of infantile paralysis in Sweden, 137 
 
 Blood-vessels, infiltration about, in poliomyelitis, 70, 
 
 Bonhoff, discovery of bodies in nuclei of glia cells in case of poliomyelitis, 
 
 — , injection of poliomyelitis virus into rabbits, 73 
 Borna's disease in horses, 133 
 
 — ■ — in relation to Heine-Medin disease, 28, 128, i2Q 
 — ■ — , nature of, 28 
 — - — , path of infection, 134 
 Boston, epidemic of infantile paralysis in, 140 
 
 Brain, abscess of, causing symptoms of cerebral paralysis in monkeys, 53, 54 
 — , microscopic changes in poliomyelitis of monkeys and man compared, 
 106, 122-124 
 
 , similar, 103-106 
 
 Briegleb, cases of infantile paralysis in Germany, 138 
 
 Broth-culture methods in Heine-Medin disease, 25 
 
 Briick, cases of infantile paralysis, 6 
 
 Buccelli, cases of infantile paralysis in Genoa, 140 
 
 Biilow-Hansen, epidemic of infantile paralysis in Norway, 137 
 
 Bull, epidemic of infantile paralysis, 136, 137 
 
 Buzzard, E. F., cases of infantile paralysis, 13Q 
 
 CARBOLIC ACID influence on poliomyelitis virus, 67 
 
 Caverley and Macphail, epidemic of infantile paralysis in Vermont, 140 
 
 Cerebrospinal fluid, examination in Heine-Medin disease, 26, 27 
 
 from monkeys after recovery from infection, antibodies in, 166 
 
 , human, alleged production of poliomyelitis in monkeys from, 80, 81 
 
200 EPIDEMIC INFANTILE PARALYSIS 
 
 Cerevesato, cases of infantile paralysis in Italy, 140 
 
 Charcot, changes in spinal cord in epidemic infantile paralysis, 4, 5 
 
 Charcot and Joffroy, pathology of infantile paralysis (discovery of loss of 
 
 ganglion cells of spinal cord), go, gi 
 Chemicals, effects on poliomyelitis virus, 67 
 Clark, Lockhart, pathology of infantile paralysis, go 
 Cocci, era of, in history of Heine-Medin disease, 24 
 Colmer, early cases of infantile paralysis, 136 
 Complement-fixation in experimental poliomyelitis, 162 
 
 Connecticut, epidemic of infantile paralysis (Heine-Medin disease) in, 141 
 Convulsions accompanying cerebral paralysis in monkeys. 53 
 Cordier, cases of infantile paralysis in France, 140 
 Cornil, pathology of infantile paralysis, 8g, go 
 Cornwall, see Devon and. Cornwall 
 Cuba, epidemic of Heine-Medin disease in, 141 
 
 Dentition, troubles of, in relation to Heine-Medin disease, 176 
 
 Devon and Cornwall, epidemic of poliomyelitis in, 130 
 
 Diarrhoea in poliomyelitis in monkeys, 54, 55, 56 
 
 Diplococcus from case of poliomyelitis causing paralysis in rabbits, 78 
 
 Disinfectant measures in Heine-Medin disease, 176 
 
 Disinfectants, behaviour of poliomyelitis virus towards, 67 
 
 Drying, resistance of poliomyelitis virus to, 66 
 
 Duchenne, change of faradic reactions of muscles in infantile paralysis, 10 
 
 Dust, experimental production of poliomyelitis in monkeys by, 148 
 
 Eckert, second attack of Heine-Medin disease, I4g 
 Eichelberg, epidemic of Heine-Medin disease in Hanover, 138 
 Encephalitis and infantile paralysis, connection between, 1 
 
 — due to Heine-Medin disease, serum diagnosis, ig 
 — , pontinea, 11 
 
 England, compulsory notification of poliomyelitis (Heine-Medin disease) 
 
 in (ign), i3g 
 — , epidemics of Heine-Medin disease in, i3g 
 Epidemics of Heine-Medin disease, 136-148 
 
 , accumulation of negative results as to aetiology, 25 
 
 Eshner, second attack of Heine-Medin disease, 149 
 
 FabriS, cases of infantile paralysis in Italy, 140 
 
 Faradic reactions of muscles in infantile paralysis, changes in, 10 
 
 Filtration of poliomyelitis virus, 62, 133 
 
 , best methods employed, 133 
 
 Flexner, attempt to cultivate virus of Heine-Medin disease, 29, 30 
 
 — , epidemics of infantile paralysis (Heine-Medin disease) in United States, 
 
 — , nystagmus accompanying cerebral paralysis in monkeys, 53 
 
 Flexner and Clark, antibodies in cerebrospinal fluid in poliomyelitis of 
 
 monkevs, 166 
 Flexner and Lewis, attempts to determine point of entrance of poliomyelitis 
 
 virus, 101 
 
 ■ , convulsions accompanying cerebral paralysis in monkeys, 53 
 
 , demonstration of antibodies in antipoliomyelitic serum, 165 
 
 1 distribution of poliomyelitis virus in organs of monkeys, 96, 97, 
 
 98, QO ,.,.-.," 
 
 — - — , effect of high temperatures on poliomyelitis virus. 66 
 
 passing poliomyelitis virus through animals, 68, 69 
 
 — perhydrol on poliomyelitis virus, 67 
 
 — — , facial paralysis in poliomyelitis of monkeys, 50, 51 
 , filtration of poliomyelitis virus, 62 
 
 , immunity of monkeys to poliomyelitis after first attack, 153 
 
 , inoculation of monkeys with virus of poliomyelitis, 43, 44, 45 
 
 , poliomyelitis virus in mesenteric glands in child, 95 
 
 , resistance of poliomyelitis virus to drying, 66 
 
 , serum-therapy in Heine-Medin disease, 172 
 
 Fbrssner and Sjovall, pathology and pathogenesis of Heine-Medin disease, 
 
 94 
 Forster, O., epidemic of Heine-Medin disease in Schleswig, 138 
 Formalin, effect on emulsion of poliomyelitis virus, 67 
 
INDEX 20I 
 
 Foulerton, A. G. R., Pasteur, W., and MacCormac, H., results of injection 
 
 of cerebrospinal fluid into rabbits, 70 
 France, epidemics of Heine-Medin disease in, 139, 140 
 Frankenau (Hesse), spread of Heine-Medin disease at, 146 
 
 Gastrointestinal route, portal of entry of poliomyelitis virus by, 135 
 
 — symptoms in poliomyelitis of monkeys, 54 
 Genoa, cases of infantile paralysis in, 140 
 Germany, epidemics of Heine-Medin disease in, 138 
 
 Giersvold, discovery of cocci in epidemics of Heine-Medin disease, 24 
 Glia cells, discovery of bodies in nuclei of, in case of poliomyelitis, 20, 
 Glycerine, preservation of poliomyelitis virus in, 64 
 — , resistance of poliomyelitis virus to, 63 
 
 Goldscheider, microscopical and cultural investigation in Heine-Medin 
 disease, 24 
 
 — pathology of infantile paralysis, Q3 
 
 Guinon and Rist, cases of Heine-Medin disease in France, 140 
 
 Hemolytic system in testing reaction in fixation of complement, 163 
 Hanover, epidemic of Heine-Medin disease in, 138 
 Harbitz, epidemic of infantile paralysis in Norway, 137 
 Harbitz and Scheel, immunity to Heine-Medin disease, i4g 
 
 , pathology and pathogenesis of Heine-Medin disease, Q4 
 
 v. Heine, J., biographical sketch of, g 
 
 — , name " spinal infantile paralysis " adopted by, 1 
 
 — , pathology of infantile paralysis, 87 
 
 — , reasons for assuming lesion of spinal cord in infantile paralysis, 88, 8g 
 
 — , stages of infantile paralysis observed by, 7 
 
 Heine-Medin disease, adoption of term by Wickman, 2 
 
 — — , antibodies from serum in case's of, 168-170 
 , atypical (marantic) forms, 131 
 
 ~j bacteriological research by author, 26 
 
 -, Borna's disease in relation to, 28, 128, i2g 
 
 , carriers of, 146-148, 176 
 
 • — 3 communication with must be cut off, 175 
 
 — — , cerebral forms, 170 
 
 , contagiousness, proof of, 144-146 
 
 , dentition in relation to, 176 
 
 , disinfectant measures in, 176 
 
 j economic and humane reasons for combating, 174, 175 
 
 , epidemics, 25 
 
 , age and sex predisposition, 142, 143, 144 
 
 ■ — , large, origin of, 141 
 
 , season of, 142, 143 
 
 , epidemiology, 136-148 
 
 , era of cocci in history of, 24 
 
 , etiology, 22-86 
 
 , accumulation of negative results, 25 
 
 , historical account, 6-13 
 
 retrospect, 3 
 
 , immunity to, I4g-i62 
 
 , clinical and epidemiological experience, 149 
 
 , immunization against, i4g-i62 
 
 3 incubation period, ,3 
 
 , Landry's paralysis in relation to, 128 
 
 , lesion, primarily vascular or perivascular, 130 
 
 , microscopical and cultural investigation, 24 
 
 , occupation in relation to prevalence, 147 
 
 , pathogenesis, 129-135 
 
 — — ■ — , problems in, 94 
 
 3 pathology and pathogenesis, 87-135 
 
 polyneuritis in relation to, 128 
 
 • ■ — ■ , in adults, 128 
 
 , primary affection of ganglion cells may occur, 130 
 
 , prodromal, 13 
 
 , prognosis, ig 
 
 , prophylaxis, personal, 175 
 
202 EPIDEMIC INFANTILE PARALYSIS 
 
 Heine-Medin disease, rabies in relation to, 128 
 , serum diagnosis of, 166-171 
 
 — — , serum-therapy, 171 
 , results, 172, 173 
 
 , spread of, along lines of traffic, 137 
 
 , stage of paralysis in, 14-19 
 
 , State regulation, 177 
 
 , strict precautions necessary, 178 
 
 , symptomatology in man, 13-21 
 
 symptoms, clinical, difficulty in explaining, 131 
 
 , prodromal, 13 
 
 , treatment by drugs, 173 
 
 , symptomatic, 174 
 
 , use of broth-cultures in, 25 
 
 , see also Paralysis, infantile; Poliomyelitis 
 
 Herpes zoster and poliomyelitis, etiology of, 170, 171 
 Hesse-Xassau, epidemic of Heine-Medin disease in, 26, 34, 13b 
 Hoffmann, cases of infantile paralysis in Germany, 138 
 — , epidemic of Heine-Medin disease in Germany, 138 
 Holland, cases of Heine-Medin disease in, 139 
 Horses, Borna's disease in, 28 ; see also Bo ma's disease 
 Hydrogen, peroxide of, effect on poliomyelitis virus, 67 
 Hydrophobia, intracellular bodies in ganglion cells in, 28 
 — , method of transmission from animal to animal, 33 
 
 — and poliomyelitis, similarity of histological changes in, 33 
 Hypersensitiveness, specific negative results in experimental poliomyelitis, 
 
 163 
 
 Immunity and immunization in Heine-Medin disease, 149-162 
 Intracellular bodies in ganglion cells in hydrophobia, 28 
 Italy, epidemics of Heine-Medin disease in, 14c 
 
 JORG, case of infantile paralysis, 6 
 
 Joest, Borna's disease in horses, 28, 133, 134 
 
 Joest and Degen, Borna's disease in horses, 128, 129 
 
 Jogichess, grouped cases of infantile paralysis in St. Petersburg (1909-10), 
 
 140 
 Joseph, injection of poliomyelitis virus into rabbits, 75 
 
 Kennedy, cases of " temporary paralysis" described by, 10 
 Key and Retzius, distribution of poliomyelitis in organs of monkeys, 99 
 Kidneys, inflammation, in poliomyelitis in man, 103 
 Kraus, influence of carbolic acid on poliomyelitis virus, 67 
 — , injection of poliomyelitis virus into rabbits, 74 
 — , serum therapy in Heine-Medin disease, 172 
 
 Krause and Meinicke, attempts to determine point of entrance of polio- 
 myelitis virus, 101 
 
 , attempts to produce poliomyelitis in rabbits, 70, 73, 74, 75, 77-86 
 
 , immunity of monkeys to poliomyelitis after first attack, 154 
 
 Landry's paralysis and infantile paralysis, similarity or identity of patho- 
 logical processes, 11, 17 
 
 Landsteiner and Levaditi, attempts to determine point of entrance of polio- 
 myelitis virus, 101 
 
 , demonstration of antibodies in antipoliomyelitic serum, 165 
 
 , durability of poliomyelitis virus in animals, 68 
 
 , effect of chemicals upon poliomyelitis virus, 67 
 
 low temperatures on poliomyelitis virus, 65 
 
 potassium permanganate and peroxide of hydrogen on polio- 
 myelitis virus, 67 
 
 , filtration of poliomyelitis virus, 62 
 
 , immunity of monkeys to poliomyelitis after first attack, 153 
 
 , inoculation of monkeys with poliomyelitis virus, 43, 44 
 
 , pathogenesis of Heine-Medin disease, 130 
 
 , resistance of poliomyelitis virus to drying, 66 
 
 — to glvcerine, 63 
 
INDEX 203 
 
 Landsteiner and Popper, experimental transmission of poliomyelitis from 
 
 human subject to monkeys, 31, 32 
 Leegaard, epidemics of Heine-Medin disease in Norway, 137 
 Leiner and von AViesner, attempts to determine point of entrance of 
 
 poliomyelitis virus, 101, 102 
 
 , demonstration of antibodies in antipoliomyelitic serum, 165 
 
 , durability of poliomyelitis virus in animals, 68 
 
 , effect of high temperatures on poliomyelitis virus, 66 
 
 passing poliomyelitis virus through animals, 68 
 
 , facial paralysis in poliomyelitis of monkeys, 50 
 
 , filtration of poliomyelitis virus, 62 
 
 , immunity of monkeys to poliomyelitis after first attack, 153 
 
 , inoculation methods of poliomyelitis virus, 99, 100 
 
 — — - — of monkeys with poliomyelitis virus, 43, 44, 45 
 
 , marasmic forms of iDoliomyelitis in monkeys, 56 
 
 , resistance of poliomyelitis virus to drying, 66 
 
 , serum therapy in Heine-Medin disease, 172 
 
 Lentz and Huntemiiller, injection of poliomyelitis virus into rabbits, 75, 
 
 79, 82 
 
 Levaditi, attempt to cultivate virus of Heine-Medin disease, 29, 30 
 
 — , effect of low temperatures on poliomyelitis virus, 65, 66 
 
 Levaditi and Landsteiner, serum therapy in Heine-Medin disease, 172 
 
 Levaditi and Stanesco, facial paralysis in poliomyelitis of monkeys, 50, 51 
 
 , relapse in poliomyelitis of monkeys, 5g 
 
 Lorenzelli, cases of infantile paralysis in Parma, 140 
 Lumbar puncture in Heine-Medin disease, 174 
 
 Lymph channels in central nervous system, spread of poliomyelitis virus 
 along, 133, 134 
 
 MacCormac, H., Foulerton, A. G. R., and Pasteur, W., results of injection 
 
 of cerebrospinal fluid into rabbits, 70 
 Man, demonstration of poliomyelitis virus in different organs in, 95 
 — , pathological changes found in experimental poliomyelitis in monkeys 
 
 compared with those in, 102 
 — , symptomatology of Heine-Medin disease in, 13-21 
 Marasmic forms of poliomyelitis in monkeys, 56 
 Marks, H. K., attempts to produce poliomyelitis in rabbits, 85 
 Massachusetts, epidemic of infantile paralysis (Heine-Medin disease) in, 141 
 Medin, cerebral forms of Heine-Medin disease, 170 
 — , epidemics of infantile paralysis in Sweden, 137 
 — , proof of connection between infantile paralysis and certain forms of 
 
 encephalitis, 1 
 Meningitis, epidemic, similarity of epidemic poliomyelitis to, 97 
 Meningo-myelo-encephalitis, disseminated, 93 
 
 Menthol as mouth-wash in prophylaxis of Heine-Medin disease, 175 
 - — ■ oil, effect on poliomyelitis virus, 67 
 Mesenteric glands in child, poliomyelitis virus in, gs 
 
 , in monkeys, poliomyelitis virus in, 98 
 
 Micro-organisms, attempts to produce myelitis by experimental injection, 30 
 Mdbius and Sanger, cases of infantile paralysis in Germany, 138 
 Monckeberg, pathology of infantile paralysis, 92 
 Monkeys, intracerebral injection of poliomyelitis virus into monkeys. 
 
 technique, 33 
 — , poliomvelitis in, alleged production from human cerebrospinal fluid, 
 
 80, 8; _ 
 
 , clinical history, 43-61 
 
 ■ — - — , demonstration in different organs, 95, 96 
 
 — - — , pathological changes compared with those in man, 102 
 
 virus passed through, injected into rabbits, 72 
 
 — , results of injection of poliomyelitis into rabbits, tested on, 76, 77 
 
 — , susceptibility to poliomyelitis virus, 42 
 
 — , transmission of poliomyelitis from human subject to, 31, 32 
 
 from one to another, 33 
 
 — , use of animals other than, for experiment, 69-86 
 
 Mouth, cleansing of, prophylactic against Heine-Medin disease, 175-176 
 Miiller, contagiousness of Heine-Medin disease, 146 
 
 Muller, E., economic and humane reasons for combating Heine-Medin 
 disease, 174, 175 
 
204 EPIDEMIC INFANTILE PARALYSIS 
 
 Mliller, E., epidemic of Heine-Medin disease in Hesse-Nassau, 138 
 
 — j season of epidemics of Heine-Medin disease, 142, 143 
 
 — , symptomatology of Heine-Medin disease in man, 13, 14 
 
 Muscles, faradic reactions in infantile paralysis, changes in, 10 
 
 Myelitis, certain forms identified with poliomyelitis, g4 
 
 — , experimental attempts to produce lesions of, comparable to Heine- 
 Medin disease, 30 
 
 Myelo-encephalitis disseminated, infiltrative, Borna's disease in horses same 
 as, 28 
 
 Nannestad, epidemic of Heine-Medin disease in Norway, 137 
 
 Nebraska, epidemic of infantile paralysis (Heine-Medin disease) in, 141 
 
 Negri, intracellular bodies in ganglion cells in hydrophobia, 28 
 
 Nerves, direct injection of poliomyelitis virus into, 100 
 
 Nervous system, complications in prodromal stage of Heine-Medin 
 
 disease, 14 
 , central, inflammatory process in, symptoms of poliomyelitis acuta 
 
 due to, 03 
 , persistence of poliomyelitis virus in other regions longer than 
 
 in, 68 
 
 , spread of poliomyelitis virus within, 132 
 
 ■ , along lymph channels, 133, 134 
 
 Netter, epidemic of Heine-Medin disease in and about Paris (igog), 140 
 
 — , facial paralysis in poliomyelitis of monkeys, 50 
 
 Netter and Levaditi, antibodies in serum from cases of Heine-Medin disease, 
 
 168 
 Neuritis, certain forms of grouped with poliomyelitis, 11 
 Neuronophagy of spinal ganglion cells in poliomyelitis, 115-121, 130 
 New Jersey, epidemic of infantile paralysis (Heine-Medin disease) in, 141 
 New York, epidemics of infantile paralysis (Heine-Medin disease) in, 140, 
 
 J 4i .... 
 
 Nobecourt and Darre, serum therapy in Heine-Medin disease, 173 
 Norway, epidemics of Heine-Medin "disease in, 136, 137, 141 
 Nystagmus accompanying cerebral paralysis in monkeys, 53 
 
 Oppexheim, ''•' encephalitis pontinea," 11 
 
 Osgood and Lukas, persistence of poliomyelitis virus in pharynx after 
 
 disappearance from nervous system, 68 
 Oxholm, outbreak of infantile paralysis in Norway, 137 
 
 Pain and tenderness in prodromal stage of Heine-Medin disease. 14 
 Painter, epidemic of infantile paralysis in Boston, 140 
 Paralysis (abortive) in Heine-Medin disease, 14 
 
 — (bulbar and cerebral) in poliomyelitis of monkeys, 40, 53 
 
 -in poliomyelitis of monkeys accompanied by convulsions, 53 
 
 accompanied by nystagmus, 53 
 
 — (bulbar and pontine) in Heine-Medin disease, 18 
 
 — (cerebral), certain kinds of, grouped with spinal infantile palsies, 11 
 -in Heine-Medin disease, 18 
 
 — ■ — in monkeys, due to brain abscess, 53, 54 
 
 — during dentition, 22 
 
 — , experimental production in animals, 30 
 
 — (facial) in polionryelitis of monkeys, 50, 31 
 
 — in Heine-Medin disease, recovery from, 20 
 , types of, 14-ig 
 
 — in poliomyelitis of monkeys, 45 
 
 , confers immunity to second attack, 153, 154 
 
 — , similar to that occurring in man, 46 
 
 — in rabbits following infection with streptococci, 78 
 , with diplococcus from case of poliomyelitis, 78 
 
 — (infantile), acute and chronic stages, 7, 8 
 , and encephalitis, connection between, 1 
 
 , and Landry's disease, similarity or identity of pathological pro- 
 cesses, 11, 17 
 , changes in faradic reactions of muscles in, 10 
 
 — - — , epidemic and sporadic, identity proved by serum test, 21 
 — , first adoption of term, 1 
 
INDEX 205 
 
 Paralysis (infantile), first occurrence in epidemics, 136 
 — ■ — , " idiopathic " or " essential, ;) 1, 23 
 , in adults, 10 
 
 — - — , sporadic, 20 
 
 , see also Heine-MecLin disease, Poliomyelitis 
 
 — of left hind limb in poliomyelitis of monkeys, 58 
 
 — (Landry's) identity with poliomyelitis, Q4 
 
 , in relation to Heine-Medin disease, 128 
 
 — ■ — , poliomyelitis acutissima in case of, 02 
 
 ■ — (spinal) in Heine-Medin disease, 15 
 
 in poliomyelitis of monkeys, 47, 60 
 
 , infantile, date of adoption of term, 1 
 
 , reasons for retention of name, 2 
 
 Paris, epidemic of Heine-Medin disease in and about (ipog), 140 
 
 Pasteur, L., method of transmission of hydrophobia from animal to 
 
 animal, 33 
 — , effect of passing virus of rabies through rabbits, 6q 
 Pasteur, W., outbreak of infantile paralysis in one family, i3g 
 Pasteur, W., Foulerton, A. G. R., and MacCormac, H. , results of injection 
 
 of cerebrospinal fluid into rabbits, 70 
 Perhydrol, effect on poliomyelitis virus, 67 
 Pes cavus following Heine-Medin disease, 16, 17 
 Pharynx, persistence of poliomyelitis virus in, after disappearance from 
 
 central nervous system, 68 
 Pia mater, cerebral and spinal, microscopic changes in monkey and man, 
 
 compared, 107-111 
 Pieper, epidemic of Heine-Medin disease in Pomerania, 138 
 Pieraccini, cases of infantile paralysis in Italy, 140 
 Platou, epidemic of Heine-Medin disease in Xorway, 137 
 Poliomyelitis acuta in monkeys, 47 
 
 , symptoms of, cause, 93 
 
 — ■ acutissima, 18 
 
 — • — -in case of Landry's paralysis, 02 
 
 -in monkeys, 46 
 
 — and herpes zoster, etiology of, 170, 171 
 
 — ■ and hydrophobia, similiarity of histological changes in, 33 
 
 — and rabies, biological connection between, from point of view of 
 
 immunity wanting, 162 
 
 — anterior acuta, date of adoption of term, 1 
 — , certain forms of neuritis grouped with, n 
 
 — , clinical and -post-mortem records of cases from which virus was 
 
 obtained for experiments, 34-42 
 — , compulsory notification in England (ign), 130 
 — , diplococcus from case of causing paralysis in rabbits, 78 
 — , discovery of bodies in nuclei of glia ceils in case of, 2Q 
 — , (epidemic), first adoption of term, 1 
 
 , in Hesse-Nassau (igog), 34 
 
 — ■ — , similarity to epidemic meningitis, 07 
 
 — in adults in relation to Heine-Medin disease, 12S 
 
 — in monkeys, abortive forms, 54, 55 
 
 , alleged production from human cerebrospinal fluid, 80, 81 
 
 — ■ — , antibodies in serum from, successful demonstration, 163-166, 168 
 
 , attempts at re-infection, 151 
 
 — ■ — , clinical history, 43-61 
 
 — ■ — , experimental, fixation of complement in, 162 
 
 , gastro-intestinal symptoms, 54 
 
 -, immunity after first attack, 151-153 
 
 , conferred if paralysis has been present, 153, 154 
 
 , incubation period, 43 
 
 , longer when filtered virus used, 63 
 
 , marasmic forms, 56 
 
 , paralysis in, 47, 4g, 50, 51, 58 
 
 , recovery from, 57, 50 
 
 , pathological changes compared with those in man, 102 
 
 , macroscopic, 103 
 
 , prodromal symptoms, 44 
 
 , prognosis bad, 60, 61 
 
 , recovery from acute stage, 57 
 
206 EPIDEMIC INFANTILE PARALYSIS 
 
 Poliomyelitis in monkeys, relapses, 59 
 
 , specific hypersensitiveness in, negative results, 163 
 
 , stage of paralysis, 45 
 
 , of repair, 125 
 
 ■ — , final, 127 
 
 , time of onset of lesions, 127 
 
 ■ , transmission, by saliva and dust, 148 
 
 — , infiltration around blood-vessels in, 79 
 
 ■ — , Landry's paralysis and certain forms of myelitis identified with. g4 
 
 — , transmission from monkey to monkey, 33 
 
 to monkeys from human subjects, 31, 32 
 
 — , see also Heine-Medin disease; Paralysis, infantile 
 
 — virus, behaviour towards disinfectants, 67 
 , cultures of, 29 
 
 j demonstration in different organs in man, 95 
 
 in monkeys, 95, 96 
 
 , difference from that of rabies, 66 
 
 , distribution and spread within organism, 94 
 
 , dry, protective inoculation with, 156 
 
 , durability in animals, 67, 68 
 
 , effect of " change of host," 69 
 
 of low and high temperatures on, 65, 66 
 
 of passing through animals, 68 
 
 , " exaltation" of, 69, 71 
 
 — — , filtered and unfiltered, difference in virulence between, 62 
 , filtration of, 62 
 
 , glandular distribution in monkeys,. 98 
 
 — - — , immunization by small doses, 157 
 
 methods, 156-162 
 
 with during incubation period, 162 
 
 when attenuated or killed by chemical means, 158 
 
 when heated, 159 
 
 in mesenteric glands in child, 95 
 
 , injection into rabbits, results, 70, 71, 73-86 
 
 , results tested by simultaneous injection into monkeys, 76, 77 
 
 , inoculation, by direct injection into nerves, 100 
 
 , intracerebral, 99 
 
 into monkeys, technique, 33 
 
 , intravenous, 100, 133 
 
 — , subcutaneous, 100 
 
 , nature of, 61-69 
 
 passed through monkeys injected into rabbits, 72 
 
 , persistence of, 176, 177 
 
 , point of attack, i2g 
 
 — ■ — , portal of entry, 101, 134, 135 
 
 attempts to determine, 101 
 
 — - — ■ by gastro-intestinal route, 135 
 
 , preservation in glycerine, 64 
 
 , resistance to drying, 66 
 
 — to glycerine, 63 
 
 after passing through animals, 63 
 
 , route to spinal cord, 133 
 
 , similarity to that of rabies, 63 
 
 — — 5 spread within central nervous system, 132 
 , susceptibility of monkeys to, 42 
 
 transmitted through the best filters, 133 
 
 used in experiments, source of, 34-42 
 
 . and serum containing antibodies, immunization with, 160 
 
 Polyneuritis in relation to Heine-Medin disease, 128 
 
 Pomerania, epidemic of Heine-Medin disease in, 138 
 
 Potassium permanganate, effect on poliomyelitis virus, 67 
 
 Potpeschnigg, diplococcus from case of poliomyelitis causing paralysis 
 
 in rabbits, 78 
 — , epidemic of Heine-Medin disease in Austria, 139 
 Prevertebral glands in monkey, poliomyelitis virus in, 98 
 Prevost and Vulpian, pathology of infantile paralysis, 90 
 Prognosis in Heine-Medin disease, 10 
 , bad in adults compared with children, 20 
 
 — in poliomyelitis of monkeys, bad, 60, 61 
 
INDEX 207 
 
 Rabbits, attempts to produce myelitic lesions in, experimentally, 30 
 
 — , effect of passing virus of rabies through, 69 
 
 — , injection of cerebrospinal fluid into, results, 70, 71 
 
 poliomyelitis virus into, after passing through monkeys, 72 
 
 , results, 70, 71, 73-86 
 
 compared with those in control monkeys, 76, tj 
 
 — , paralysis in, caused by infection with diplococcus from case of polio- 
 myelitis, 78 
 
 — , paralysis in, caused by infection with streptococci, 78 
 
 Rabies and poliomyelitis, biological connection between, from point of 
 view of immunity wanting, 102 
 
 — , in relation to Heine-Medin disease, 128 
 
 — , virus of, and poliomyelitis virus, 63, 66 
 
 , effect of, passing through rabbits, 6g 
 
 Reece, epidemic of poliomyelitis in Devon and Cornwall, 139 
 
 Respiratory tract, complications in prodromal stage of Heine-Medin 
 disease, 14 
 
 , lower, entrance of poliomyelitis virus by, 101 
 
 Rissler, pathology of infantile paralysis, 02 
 
 Roger and Damaschino, pathology of infantile paralysis, qi 
 
 Romer, P. H., bacteriological research in Heine-Medin disease, 26 
 
 , injection of poliomyelitis virus into rabbits, 71 
 
 Russia, cases of Heine-Medin disease in, 140 
 
 St. Petersburg, cases of infantile paralysis in (igog-io), 140 
 
 Saliva, experimental production of poliomyelitis in monkeys by injections 
 of, 148 
 
 San Francisco, epidemic of infantile paralysis in, 140 
 
 Scandinavia (see Norway, Sweden) 
 
 Schleswig, epidemic of Heine-Medin disease in, 138 
 
 School infection of Heine-Medin disease, 146 
 
 Schultze, discovery of cocci in Heine-Medin disease, 24 
 
 Scoliosis, following Heine-Medin disease, 16, 17 
 
 Selter, infection of rabbits with streptococci causing paralysis, 78 
 
 Serum and virus containing antibodies, immunization with, 160 
 
 — (antipoliomyelitic), specific antibodies present in, 163-166, 168 
 
 Serum-diagnosis of encephalitis due to Heine-Medin disease, ig 
 
 ■ of Heine-Medin disease, 166-171 
 
 — •, of identity of infantile paralysis in sporadic and epidemic forms, 21 
 
 Serum-therapy of Heine-Medin disease, 171 
 
 , results, 172, 173 
 
 Siemerling and Dauber, microscopical and cultural investigation in Heine- 
 Medin disease^ 24 
 
 Simonini, cases of infantile paralysis in Italy, 140 
 
 Spain, epidemics of Heine-Medin disease in, 140 
 
 Spinal cord, anterior horns, vulnerability in Heine-Medin disease, 131 
 
 ■ , blood-vessels of, infiltration, in poliomyelitis, 111, 112 
 
 , ganglion cells, alterations in poliomyelitis of monkeys and man, 11^ 
 
 ■ , hypersemia, haemorrhages and degeneration in Heine-Medin 
 
 disease, 131 
 
 , primary lesion of, occurring in Heine-Medin disease, 130 
 
 -, implication in infantile paralysis, Heine's reasons for postulating, 
 
 88, bg 
 
 , loss of ganglion cells in infantile paralysis, go 
 
 , macroscopic changes in poliomyelitis of monkeys and man, similar, 
 
 103-106 
 
 -, microscopic changes in poliomyelitis of monkeys and man com- 
 pared, 105, 106, 107, 111-122 
 
 , route of poliomyelitis virus to, 133 
 
 Spleen, swollen, in poliomyelitis in man, 103 
 
 Stephens, negative etiological results in Heine-Medin disease, 25 
 
 Sterne, second attacks of Heine-Medin disease, 150 
 
 Strauss, alterations in ganglion ceils in poliomyelitis. 115 
 
 Streptococci, infection of rabbits with, causing paralysis, 78 
 
 Striimpell, cases of infantile paralysis in Germany, 138 
 
 — , connection of certain forms of neuritis with poliomyelitis by, 11 
 
 — , etiology of epidemic infantile paralysis, 5, 23 
 
208 EPIDEMIC INFANTILE PARALYSIS 
 
 Submaxillary glands in monkeys, poliomyelitis virus in, q8 
 Sweating, excessive in prodromal stage of Heine-Medin disease, 14 
 Sweden, epidemics of Heine-Medin disease in, 136, 137, 141 
 Switzerland, cases of Heine-Medin disease in, 139 
 
 Temperatures, low and high, effect on poliomyelitis virus, 65, 66 
 
 Thermana?sthesia in Heine-Medin disease, 16 
 
 Thymol, effect on poliomyelitis virus, 67 
 
 Traestena (Norway), school infection of Heine-Medin disease at, 1 j6 
 
 Traffic, spread of Heine-Medin disease along lines of, 137 
 
 ULTRA-MICROSCOPE, discovery of small, rounded bodies under, 28 
 United States, epidemics of Heine-Medin disease in, 140, 141 
 Urotropin in Heine-Medin disease, 173, 174 
 
 VERMONT, epidemic of infantile paralysis in, 140 
 Virus of Heine-Medin disease (see Poliomyelitis virus) 
 
 WEST, C, " paralysis of the morning,"' term proposed by, 10 
 Westphalia, epidemic of Heine-Medin disease in (1909), 26, 27, 138 
 Wickman, adoption of term Heine-Medin disease for spinal infantile 
 
 paralysis, 2 
 — . clinical and histological studies of Heine-Medin disease, 13 
 — , contagiousness of Heine-Medin disease, 146 
 — , epidemics of Heine-Medin disease in Sweden, 137 
 — , epidemiology of infantile paralysis, 5 
 , identity of Landry's paralysis and certain forms of myelitis with 
 
 poliomyelitis, established by, 04 
 — , immunity to Heine-Medin disease, 150 
 — , microscopic changes in brain in poliomyelitis in monkeys and man 
 
 compared, 122, 123 
 — , neuronophagy of spinal ganglion cells in poliomyelitis, 115-121 
 — , pathology and pathogenesis of Heine-Medin disease, 93, 94 
 — , symptomatology of Heine-Medin disease in man, 13, 14 
 
 Zappert, contagiousness of Heine-Medin disease, 147 
 
 — , immunity to Heine-Medin disease, 149 
 
 — and Neurath, epidemic of Heine-Medin disease in Austria. 138 
 

 "V^G^ 
 
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