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 THE N. Y. STATE VETERINARY COLLEGE. 
 
 1897 
 
Cornell University Library 
 
 RC 311.K76a 
 
 Aetiology of tuberculosis 
 
 3 1924 000 247 027 
 
The original of tiiis bool< is in 
 tine Cornell University Library. 
 
 There are no known copyright restrictions in 
 the United States on the use of the text. 
 
 http://www.archive.org/details/cu31924000247027 
 
ETIOLOGY 
 
 OF 
 
 TUBEI^CULOSIS 
 
 Dr. R. KOCH, 
 
 Privy Cotmcil. 
 
 Translated by Rev. T. SAURE, 
 
 Traiisactinns of the Massachusetts Veterinary Medical Association. 
 
 Reprinted from the America7i Veterinary Review. 
 
 New York : 
 
 WILLIAM R. JENKINS, 
 
 Veterinary Publisher and Bookseller, 
 
 S51 & 8^3 Sixth Avenue. 
 
 i8go. 
 
PEEFACE. 
 
 Dr. Koch's treatise on the .Sltiology of Tubercolosis, has been translated 
 with the authorization of the author, and is presented to the medical and 
 veterinary professions of the United States as the most remarkable work on 
 the subject. It is reprinted from the American Veterinary Review, and the 
 translation is due to the Massachusetts State Veterinary Medical Association, 
 who recognized its importance and undertook the labor of the work. The 
 present edition is due to the demand for the treatise in its entirety, and 
 although it is issued without the illustrations of the costly German edition, 
 it will be found of the greatest advantage to all investigations in the subject. 
 
 That the bacillus of Koch is the cause of tubercular disease ; that to these 
 are due all the different lesions of the various tissues in which it is found 
 implanted ; and that it is then invariably present, though, perhaps at times, 
 difficult to discover, to color, or to isolate ; and that, unless it is there, tuber- 
 culosis DOES NOT EXIST — all this is proved beyond question or doubt in Koch's 
 " .SJtiology." The modes of development, the processes of the biological 
 sJudies which are required for the investigation ; everything discoverable, in 
 fact, connected with this bacillus, are minutely, carefully, and thoroughly 
 described and presented by the author to the inquiring student. "With this 
 work properly appreciated and well studied, there is no longer any reason 
 for error of diagnosis in that fatal affection. The lesions are in many 
 instances so characteristic that any error can scarcely be possible, and yet 
 how frequently may it happen that lesions, of the Inngs, for instance, often 
 peculiar, may be of a tuberculous aspect and yet entirely different in their 
 nature ! The pseudo-tubercules of the lungs, sometimes encountered, have 
 no doubt in some instances led to a diagnosis of alleged phthisis, which 
 would have been of an entirely different nature had the teachings of the 
 author been followed, and the truth discerned, which the absence of the 
 bacilli would have made certain, if it had but been rightly interpreted. 
 
 " .aetiology of tuberculosis," which has filled so important a place among 
 German scientific authorities, may now perform the same good office for 
 English-speaking veterinarians, and by such of us as may unfortunately 
 have much to do with this disease in the United States, we hope it will be 
 recognized as an instructor and assistant beyond any possibility of rivalry or 
 cavil, or chance of supercedure. 
 
.ETIOLOGY OF TUBERCULOSIS. 
 
 A series of investigations of the iEtiology of Tuberculosis which I have been 
 making within the last few years have led me to results which were first reported 
 before the Physiological Society of Berlin, March 24th, 1883 (Berliner klinischo 
 Wochenschrift, 1883, No. 15). My communications at that time, however, could 
 only embrace the most important points, while the more minute description of the 
 attempts was necessariJy reserved for a detailed report. Since then, by continued 
 investigations, many gaps have been filled and new matter added. The report of 
 my labors in the investigation of the ajtioloiry of tuberculosis, completed and en- 
 larged by these researches, is given in the following. 
 
 The question whether tuberculosis is a disease dependent upon transmitted 
 disease-germs can be approached in different ways, as this has in fact been done. 
 It has been attempted to secure certainty, partly with the aid of clioical observa- 
 tions, partly by means of anatomical and also by experimental investigations. 
 Most uncertain are the results of the experience gathered at the sickbed. It is 
 true, cases occur in the experience of every physician with fair practice, in which 
 he cannot fail to see a transmission of tuberculosis from one person to another. 
 Then, however, follow numerous cases in which every possibility of infection seems 
 to be excluded. Attempts have been made repeatedly to prove the contagious 
 nature of phthisis, but they must be looked upon as failures, as such views have 
 never found acceptance among scientists. Some clinical authorities, to be sure, 
 have not lost view of the possibility of contagion, but on the whole physicians 
 consider phthisis a non-contagious disease, proceeding from constitutional anom- 
 alies. An indication of the infectious charai ter of tuberculosis, which cannot be 
 ignored, was given by pathological anatomy, when Bulil called attention to the 
 connection of miliary tuberculosis with kiise-hcrden,* (a German technical term 
 of which I do not know the meaning in the English language) and offered the prop- 
 osition that general tuberculosis is to be looked upon as a disease which is 
 brought about by the resorption of a virus present in the primary kiisc-herd 
 (cheesy-nodule), hence as it were, by auto-infection. As to the manner in which 
 tuberculous virus spreads itself through the body, the discoveries of Ponfick in 
 regard to the thoracic duct and of Weigert in regard to veinous tubercles in miliary 
 tuberculosis have given light. However, these facts only prove the spread of tub- 
 erculous virus in the body itself, without proving the transmission from one 
 individual to another, in which latter the contagious nature really consists. With 
 this last question experimental pathology has occupied itself in the most searching 
 manner. The course taken in experimental investigations of the infectious nature 
 of tuberculosis has been described of late very minutely, (cf, Johne, Die Ge- 
 schichte der Tuberculose. Leipzig, 1883), so that I can omit the historical details 
 and confine myself to a few remarks on the more inportant heads. 
 
 •CUeesy nodules. — 9. 
 
* JSTIOLOGY OF TUBEECULOSI8 
 
 Solitary, incomplete and negative attempts to generate tubercnlosis artificially 
 (vera made towards the end of the last century. The first successful attempts 
 were made by Klencke, who by inoculation of miliary and infiltrated tubercles 
 from the human being into the cervical veins r-f rabbits, brought about a wide- 
 spread tuberculosis of the lungs and liver. Klencke must therefore be pronounced 
 the discoverer of experimental tuberculosis. He did not continue his attempts, 
 and so they were almost forgotten. In a systematic and thorough manner experi- 
 mental tuberculosis was worked out by Villemin. He not only inoculated tuber- 
 culous substances from the human subject, but also from the pearl disease of cattle, 
 and showed by experiment the identity of pearl disease and tuberculosis. Ville- 
 min's investigations seemed already, by the number of experiments, by their 
 careful execution and comparison with opposing attempts bearing upon the same 
 question, to have decided the question in favor of the infection theory. Never- 
 theless the numerous investigators who repeated Villemin's attempts according 
 to the methods suggested by him or in modified ways, arrived at very contradictory 
 results. The defenders of the mfcction theory, especially Klebs, souglit to improve 
 the experimental technique and to free it from the errors clinging to it; the op- 
 ponents, on the contrary, strove to prove that the tuberculous substance possessed 
 no virulent properties, and true tuberculosis could be produced by inoculation 
 with material in which tuberculosis did not exist. This dispute was first settled 
 by the experiments of Cohnheim and Salomonsen who, with this end in view, in- 
 oculated the anterior chamber of the eyes of rabbits. It was an exceedingly 
 happy idea to make use of the rabbit eye as the place of inoculation. From the 
 nature of the case, those cases in which tuberculous substance only has been inoc- 
 ulated must be distinguished from those in which other infectious material has 
 been combined with the tuberculous virus. In subcutaneous inoculation, such 
 materials often produce more or less widespread caseous infiltrations, which are 
 not unlike the tuberculous cheesy products. In the eye, on the contrarj', they cause 
 an inflammation which rapidly runs its course, which can in no case be mistaken 
 for the inoculated tuberculosis, which is slow and unique in its development. 
 This inoculated tuberculosis, when the experiment is successful, takes such a 
 course that it is always manifest to the investigator. After a somewhat prolonged 
 stage of incubation little gray nodules appear in the iris, scarcely visible to the 
 naked eye and proceeding from the transplanted portions of tubcrculnus substance. 
 The number of these nodules increases gradually, they themselves grow, become 
 yellowish in the center, become cheesy and show as well macroscopically as mi- 
 croscopically all the typical characteristics of genuine tuberculous nodules. 
 
 Tuberculous infection is, moreover, not confined to the eye, but spreads itself 
 later through the entire organism; it attacks especially the neighboring lymphatic 
 glands, the lungs, spleen, liver and kidneys. According to the united testimony 
 of Cohnheim and Salomonsen and all other experimenters, who have repeated 
 these attempts, an iris-tuberculosis has in no case followed the inoculation with 
 non-tuberculous substances. More than this, a spontaneous case of iris-tuberculosis 
 in rabbits has never been observed. This method of infection is thereiore su- 
 perior to all others in so far as that the influence of unintentional errors in attempt 
 is shut out, errors which so easily creep into the experiments in subcutaneous 
 inoculation and in transplantation into the abdominal cavity. The chance of 
 
^ETIOLOGY OP TUBERCULOSIS. O 
 
 mistaking artificial tuberculosis for that arising spontaneously is also completely 
 excluded. Therefore in comparing the attempts of Cohuheim and Salomonsen 
 with those previously made, they must be admitted to be completely free from 
 objection, and by them it is proved that the most different tuberculous substances 
 contain a specific and individual element. 
 
 Of what character this infectious matter might be, whether it be formed by 
 means of organisms independent, or provided with unvarying properties, which 
 force themselves into the body as parasites and communicate tuberculosis to it, or 
 whether the infectious material exists only in certain conditions of the body and 
 consists of organized or unorganiz2d formations arising from its own ingredients, 
 was a question that for the time being could not be decided. But after the results, 
 which have been attained of late years regarding the cetiology of many infectious 
 diseases, the possibility that also the cause of tuberculosis was to be sought in 
 some sort of micro-orgamsms, seems to be indicated. In order to obtain light on 
 this point, it was necessary to make use of all that experience which had proved 
 itself useful in the examination of other infectious diseases, and the same course 
 of investigation was to be chosen which in other cases had shown itself most to 
 the purpose. To make the best use of these advantages, the attempts were to be 
 made in the following manner: In the first place, it must be decided whether form 
 elements, not belonging to the elements of the body, or arising from them, are 
 present in the diseased parts. If the existence of such can be proved, then we 
 must investigate whether the same be organized and whether they offer any signs 
 of independent life, among which independent motion, (for which molecular mo- 
 tion is very often mistaken), growth, increase and generation are to be reckoned. 
 Further, the relations to their surroundings, the conduct of the components of 
 the neighboring textures, their diffusion in the body, their appearance at the va- 
 rious stages of the disease, and other circumstances must be traced, which, with 
 more or less probability, show a primary connection between these formations 
 and the disease. It is possible that the facts gained in this manner may afford 
 such proof that only the most extreme scepticism can maintain that micro-organ- 
 isms found are no cause, but only an accompaniment of the disease. Often, of 
 course, this objection is justified, and therefore it is necessary for a complete 
 system of proof that one should not confine himself to showing the co-existence 
 of the disease and parasites, but that, more than this, these parasites must be 
 shown to be the real cause of the disease. This can only be done by removing 
 the parasites from the diseased organism completely, and freeing them from all 
 products of the disease to which a hurtful influence could be ascribed, and that 
 by the introduction of the isolated parasites mto the healthy organism, the dis- 
 ease with all its peculiar characteristics should be produced anew. An example 
 may serve to explain what has just been said. If the blood of animals which 
 have died from inflammation of the spleen be examined, there are always 
 found therein numerous minute, rod-shaped, colorless, motionless forms. One 
 could not see immediately that these minute rods are of a vegetable nature, and 
 indeed in the beginning they were often held for lifeless crystalline bodies. First 
 from the circumstance that they were seen to grow from spores, and that from 
 the spores little rods were developed anew, could it be decided with certainty 
 that they possessed life and belonged to the lowest class of plants. Further, 
 
6 iHTIOLOGY 01' TUBEECULOSIS. 
 
 • 
 when the very smallest amount of the blood of an animal dying of inflam- 
 mation of the spleen is inoculated into another animal, said animal invariably 
 dies of the same disease, and it also contains the little rods, the so-called "bacilli" 
 of inflammation of the spleen. This does not prove, however, that by the 
 inoculation of the little wands, the disease was communicated. In order to know 
 whether the bacilli, and not other components of the blood of inflammation 
 of the spleen, produces said inflammation, the bacilli must be separated from the 
 blood, and be inoculated alone. 
 
 The isolation of the bacilli can be ascertained with most certainty by contin- 
 ued cultivation apart from all other things. To this end, a small quantity of 
 blood containing bacilli is placed upon some fixed nutrient soil, on which the 
 bacilli are able to grow, f Jr instance, nutrient gelatine or boiled potatoes. Here 
 they soon begin to increase very rapidly, while the other components of the blood, 
 crrpusclcs and serum, remain unchanged. After two or three days, when the 
 bacilli have formed a dense mass of spore-hoIding threads, the smallest possible 
 of the no longer blood-red, but whitish looking mass, is taken and again placed 
 upon nutrient gelatine or boiled potatoes. The bacilli increase in exactly the 
 same manner as in the first planting, and form a dense white mass on the potato, 
 and already in this second transplanting the most careful examination with the 
 microscope will scarcely show any traces of the other components of the blood. 
 In like manner the continued transplanting is carried on. After the third or 
 fourth, the bacilli may be considered free from all other parts of the blood, which 
 at first were planted with them. If the transplantations now are repeated twenty 
 or fifty times, or still oftener, then it may be concluded with all imaginable cer- 
 tainty, that not the least taint of the disease clings to the bacilli. Even inter- 
 nally they could hide nothing of that kind ; for the finest planted bacilli are also 
 no longer present, and their descendants for many generations have obtained the 
 necessary material for their growth from their fostering soil, the potato. The 
 pure breed obtained in this way has no connection with the diseased organism 
 from whose blood the first planting came, and with the products of disease, which 
 belong to animal metamorphosis. Nevertheless, as soon as they are inoculated 
 into a healthy animal, they produce the fatal disease. The inoculated animal 
 sickens as quickly and with the same symptoms as if it had been inoculated with 
 blood fresh from a diseased animal, or had spontaneously become diseased with 
 inflammation of the spleen, and in its blood appear the same innumerable 
 bacilli as in the natural disease, which have the same properties as the well known 
 bacilli of inflammation of the spleen. In view of these facts, thtre is no 
 other explanation, than that said bacilli are not an accompaniment of inflam- 
 mation of the spleen, but the real cause of this disease. Now inflammation 
 of the spleen does not always present the same clinical appearance; ils form 
 varies in the difllerent species of animals ; in the case of man it can run its 
 course with the symptoms of a general infection, without prominent local dis- 
 turbances, or it can remain purely local and confine itself to a certain point on 
 the outer skin, on the gut, or on the larynx. Nevertheless also in these cases, if 
 the characteristic bacilli are found in the diseased places, we must consider them 
 as the cause of the disease ; for their disease-producing qualities are known to 
 us, and wo cannot very well imagine that in the tissues of the same organism the 
 
^riOLOGY OF T0BEECTJLOSIS. i 
 
 bacilli are at one time harmless, at another time disease-producing parasites. 
 These conclusions are so indisputable that probably nobody questions them, and 
 that in science the bacilli of inflammation of the spleen are considered the 
 cause as well of the usual typical disease as appearing in our domestic animals, 
 as also of the clinically varying type which appears in man. 
 
 The course just sketched, which those who strove to prove the parasitic 
 nature of inflammation of the spleen have taken with success, and the con- 
 clusions necessarily obtained from the results, I have placed at the foundation of 
 my investigation of the tetiology of tuberculosis. These had to employ them- 
 selves in the first place with the proof of disease-producing organisms, then with 
 their isolation, then with their inoculation. I now go over to the description of 
 these single divisions of the investigation. 
 I. — Proof of ths presence of disease-producing organisms in the organs changed hy 
 
 tuberculosis and in the separation of the latter. 
 
 Disease-producing organisms, which have the size of inflammation-of-the- 
 spleen bacilli and like these, appear in the blood in large numbers, or those which, 
 like the " nekurrensperochaeten " attract the eye, offer no especial difficulties in 
 investigation, and the proof of such micro-organisms can be obtained by ordinary 
 optical helps. The case is different, however, when it is necessary to prove the 
 existence of minute bacteria present in the tissues in only small numbers, especi- 
 ally when cells are heaped up or broken down in the spots concerned, which is 
 almost always the case. Then it is necessary to use the more delicate technical 
 helps of microscopy, as especial methods of preparation and differential coloring, 
 and to pursue the investigations with the best optical apparatus, oil-immersion 
 systems and Abbe's illuminating apparatus. 
 
 Also in regard to tuberculosis it was to be expected that to show that special 
 disease-producing organisms do actually exist, might offer special difficulties, as 
 they had already been much sought for, and nothing found that could give con- 
 fidence in their existence. I began investigations with material in which infec- 
 tious matter might be expected with certainty, for instance, in freshly developed 
 and still grey tubercles from the lungs of animals which had been killed three or 
 four weeks after inoculation. From these lungs, hardened in alcohol, sections 
 were made and examined according to the most approved methods for proving 
 the existence of bacteria. Grey tubercles were also crushed, spread out on glass 
 covers, dried, and then examined with reference to the existence of micro-organ- 
 isms. All attempts to find bacteria or other micro-organisms in these prepared 
 specimens proved unsuccessful. In former experiments it had been attempted to 
 color the bacteria as strongly and as differently from the surrounding tissue as 
 possible, and in such attempts it had been proved that in certain cases the addi- 
 tion of alkalies to the color-solutions offered essential advantages ; therefore this 
 treatment was adopted. Of the usual analine color the methyline blue will bear 
 the greatest addition of alkali, on which account this coloring material was 
 chosen, and just so much potash-lye was added to a watery solution of the same 
 as to form no precipitate, and that the liquid remained clear. For the prepara- 
 tion of this mixture 1 ccm. of a concentrated alcoholic methyline-blue solution 
 and 200 ccm. of distilled water were mixed, well shaken and during repeated 
 shaking 0.3 ccm. of 10 proc. potash-lye was added. When glass-covered prepara- 
 
8 ETIOLOGY OP TUBEECULOSrS. 
 
 tions had been treated twenty-four hours ■with this color solution, there appeared 
 in the tuberculous mass very fine stafE-shaped forms, which, as further investiga- 
 tion proved, had the power of increasing and forming spores, and therefore be- 
 long to the same group of organisms as the inflammation-of-the-spleen bacilli. 
 In section preparations it was incomparably more difficult to recognize these 
 bacilli among the thickly heaped grains and masses of detritus, and it was there- 
 fore attempted, following the example of Weigert, who, succeeding in the coloring 
 of the inflammation-of-thc-spleen bacilli a different color from the surrounding 
 tissues, to make the tuberculous bacilli more plainly visible, by similar differen- 
 tiating color reaction. This end was reached by the use of a concentrated watery 
 solution of vesuvian, with which the blue colored, covered glass preparations and 
 section preparations were treated so long, till to the naked eye, it seemed colored 
 brown. Under microscopic examination it was then seen that only the previously 
 blue-colored cell grains and the products of their disorganization had taken the 
 brown color, but that the tuberculous bacilli remained a beautiful blue color, and, 
 in consequence of this were very plainly to be distinguished from their surround- 
 ings, so that even in the masses of grains, thickly heaped together, they were 
 easily recognized. In the use of methyline blue in the manner just described, the 
 bacilli, however, do not take a very intense color, and it requires a certain amount 
 of practice to be able to prove their existence everywhere in tuberculous objects. 
 
 Another method which gives to the bacilli a very strong color, we owe to 
 Ehrlich. I use the same now exclusively, and earnestly recommend it to all 
 who are beginning their studies of tuberculous bacilli. Eurlich's method has 
 since received many unimportant modifications, partly improvements. Among 
 the latter I would reckon the proportions of solutions as settled by Weigert and 
 the shortening of the color solution, a change recommended by Rindfleisch. If 
 I describe the method in which I use Ehrlich's treatment as exactly as possible, 
 I am nevertheless not of the opinion that the modification which I have followed 
 is the best, or that just as good results are not to be gained by other modifications 
 of the treatment. But the coloring of the tuberculous bacilli appears still to offer 
 difficulties to many investigators, and for this reason, it will certainly not seem 
 superfluous to give as exact directions as possible for the method of coloring. 
 
 In order to prepare the color solution, aniline water and saturated alcoholic 
 solutions of methyl violet (to be distinguished from methyline blue) or fuchsine 
 are necessary. The aniline water is prepared in the following manner : About 5 
 ccm. of pure aniline, an oil-like liquid, at first colorless, afterwards becoming 
 brown, is poured into 100 ccm. of distilled water and this mixture is shaken re- 
 peatedly. From three to four per cent, of aniline dissolves in the water and the 
 rest remains in the bottom of the dish in the form of thick drops. After a sat- 
 urated solution of aniline in water has been formed in this way, which is the 
 case after about half an hour, this aniline water is filtrated through a filter, which 
 has been moistened in order to separate it from the rest of the undissolved ani- 
 line. The filtrate must be clear as water and colorless, and no little drops of 
 aniline must be suspended in it. If such have passed the filter, the liquid must 
 be filtrated again. 
 
 One obtains the second ingredience of the color solution, the saturated solu- 
 tion of methyl violet, by taking not too small a quantity (20 grm.) of dry methyl 
 
ETIOLOGY OP TUBEEODLOSIS. 9 
 
 violet in a well closing glass vessel, pouring over it 100-150 ccm. of absolute 
 alcohol and shaking it repeatedly. After standing a da}', there must still he un- 
 dissolved methyl violet at the bottom of the vessel, which of course can also be 
 dissolved and made use of by gradually pouring on more alcohol. When in place 
 of methyl violet, fuchsine is used, which seems to offer certain advantages for 
 permanent preparations, one also proceeds in the just described manner. 
 
 After this, the alcoholic methyl violet solution and the aniline water are to 
 be mixed, and according to Weigert in the proportion of 100 ccm. aniline water 
 to 11 ccm. methyl violet solution. I add to this mixture 10 ccm. of absolute al- 
 cohol, because I have found that then the color solution remains usable in a well 
 closed glass for about ten days and does not need to be filtered each time before 
 using. 
 
 The preparations which are to be examined with referei.ce to tuberculous 
 bacilli are to be prepared in the following manner : Covering glasses are to be 
 freed from fat and all other extraneous matter, which might prevent adhesion of 
 the substance to be examined, by washing in nitric acid and cleaning with alco- 
 hol. The substance is then to be spread out on the covering glass in as thin a 
 section as possible. This procedure succeeds best when soft caseous masses are 
 treated ; they can be spread out evenly and thin with a scalpel or a needle. Fir- 
 mer, crumby caseous masses must be carefully crushed with the scalpel and ar- 
 ranged on the glass by spreading out repeatedly. Still more difficult is it to 
 prepare a little tuberculous knot, which possesses a compact consistence. It 
 must be completely crushed and pressed to pieces on the covering glass. The 
 preparation of covering glasses with sputum also demands a special technique. 
 One must not content himself with taking any chance Jist of mucus from the 
 sputum, since the sputum consists not only of the secretion of the diseased parts 
 of the lungs, but also of bronchial secretion and mucus from the mouth and nose. 
 It is on this account necessary to examine only those parts of the sputum which 
 have separated themselves from the diseased lungs, that is to say, the yellowish 
 lumps which often swim solitarily in the frothy slimy liquid, which to be sure 
 often forms the greatest part of the sputum. Such a lump of this yellowish, ex- 
 tremely tough mass should be drawn to the edge of the glass, then a little bit of 
 it separated with the scalpel, drawn out of the liquid and on to the inner wall of 
 the glass. Here it can easily be further divided, and be taken off in as large par- 
 ticles as one wishes to transfer to the Covering glass. On fhis it is spread out 
 very evenly and thinly, and any residue should be brought to a corner of the cov- 
 ering glass, and from there removed with blotting paper. 
 
 After the covering glass has been prepared in this manner, the section spread 
 out upon it must be allowed to become thoroughly dry. Not until this is the case 
 can the covering glass be heated temporarily, in order to make the section insolu- 
 ble in watery fluids, with which it is now brought in contact. The covering glass 
 can be put into a drying box heated to 110° for twenty minutes, or one can hold 
 the covering glass with a pincette, and draw it several times, not too quickly, 
 through a gas or spirit flame. The prepared section of the covering glass is dur- 
 ing this process to be on the upper side and is not directly touched by the flame. 
 That the forms of the bacteria cells, etc , which occur in the section are not 
 changed in the least by this careful process, can be shown by the following ex- 
 
10 ^TIOLOSY OF TUBKECULOSIS. 
 
 periment. Of several covering glasses, provided -with a dried on section, let tbe 
 first not be Iieated at all, the second drawn once tlirough the flame, the third 
 twice, etc. When after this the covering glasses are treated with color solutions, 
 it appears that the coloring of the cell grains and bacteria shows r.o difference 
 between the one not heated at all and those drawn through the flame from one 
 to four times. Also the forms remain unchanged. If the heating is carried far- 
 ther and the covering glasses oftener drawn through the flame, the bacteria 
 gradually lose the power of taking the coloring material, while the cell grains 
 become colored even after very intense heating. In the covering glasses which 
 have not been heated the section separates itself more or less, often entirely, also 
 the dissolving " eiwoisskiirper " (white-of-egg bodies) form with the coloring 
 matter precipitates, which cover the section and make the recognition of bacteria 
 very difficult and even impossible. Better results are given by the covering 
 glasses which have been once or twice drawn through the flame, but those drawn 
 through three times give the best. One of these last the section clings uniformly, 
 the " eiweisskorper " are insoluble or so nearly so that no more precipitates are 
 formed, also the bacteria and cell grains take r.he color, with an even degree of 
 intensity, while the surrounding substance remains wholly or almost wholly un- 
 colored. On this account I always proceed thus: After the sections spread out 
 on the covering glasses have become completely dry, which always takes place in 
 a few minutes, I draw them three times with moderate quickness through a Bunsen 
 burner. The color-solution is placed in a watch glass or a flat vessel, and after the 
 heating the covering glass is laid face downward on the liquid, that it swims. 
 One must be careful that there are no air bubbles under the glass, as otherwise 
 the section would not he wet in these places and therefore not colored. Then 
 let the color-solution be so far heated that it just begins to bubble, and after 
 once boiling leave the coloring glass upon it about ten minutes; the result will be 
 a sufficiently powerful coloring. Better results are nevertheless reached when 
 the covering glass swims for several hours on the unheated solution. In all diffi- 
 cult cases, when one wishes to prove the existence of single bacilli, it is well to 
 leave the covering glass twelve hours or longer in the color-solution. 
 
 When one wislics to examine sections of tissues with reference to tuberculous 
 bacilli, pieces of the organ in question, not too large, are to be well hardened in 
 absolute alcohol. Other hardening processes make difficult or even hinder the 
 coloring of the bacilli. Tlie sections netd not be very thin, because by means of 
 the double coloring, single bacilli can be distinguished very easily even in quite 
 thick sections. Nevertheless, it is more to the purpose to prepare large sections, 
 since the distribution of the bacilli is often very irregular, therefore it is possible 
 that in email sections no bacilli may be found. The use of the microtome in the 
 preparation of the sections is for this reason almost invaluable. The sections are 
 immediately laid into the color-solution and remain in the same at least twelve 
 hours. They can remain in it several days without injury. 
 
 The sections as well as the layer clinging to the covering glass have, when 
 taken out of the cjlor-solution after the given time, a dark blue, almost black-blue 
 color. In this condition all parts of the tissue are almost evenly dark colored, 
 and it is scarcely possible to recognize the coarser structures. In order to make 
 the preparation suitable for microscopic investigation, a great part of the coloring 
 
ETIOLOGY OF TCBEECULOSIS. 11 
 
 material must be removed again. Tliis can be done i:i various ways. In the 
 method originally used by me, of coloring with all^aline rautliyline-bluo solution, 
 I liad found tliat the blue coloring of the constituent parts of the tissue cou'.d be 
 driven out by treating with a solution of vesuviau. The same can ''c carried out 
 in the preparations which are colored according to Ehrlich's method. Wlicn 
 these preparations are rinsed off in water and then put into a concentrated watery 
 solution of vesuvian, moved bacli and forth in the same, and finally put into 
 alcohol, one succeeds in almost completely drawing out the dark blue roloiing. 
 The preparations, nevertheless, lose their color more quickly and completely by 
 Ehrlich's method of treating them with nitric acid. That this can be done by 
 other aniline coloring materials, as for example the above mentioned vesuvian, 
 I have mentioned only for the reason that by many the effect of mtric acid has 
 been erroneously held for something specific, but this is not the case, since other 
 acids work similarly. 
 
 For taking the color out of the preparations, nitric acid, which has been diluted 
 with two parts of water, is commonly used. So strong a concentration of the 
 acid is nevertheless not absolutely necessary, and of late I use acid diluted with 
 from three to four parts of water. Perhaps one can go even farther in the dilu- 
 tion. One should take care, however, that the nitric acid is free from nitrous 
 acid. 
 
 When I spoke of the uncoloring of preparations by means of nitric acid, I fol- 
 lowed the description which Ehrlich gave of his process. By the treatment of 
 the covering-glass preparations with nitric acid, this term is exact, when the 
 preparations are not intensely colored ; after a stronger coloring, which gives decid- 
 edly bettor and more reliable results, the nitric acid after a few minutes fails to 
 take all color from the dyed section, and section preparations, which, as it has 
 already been carefully shown, must be colored a longer time and very intensely, 
 always keep, after the nitric acid treatment, quite a darli colormg. The ex- 
 pression " uncolor " is not to be understood literally. The failure of bacilli-color- 
 ing appears in most cases to have had its foundation in this very thing. The 
 experimenters thought that the preparations after treatment with nitric acid must 
 be wholly colorless, and in order to reach this, partly colored too little the prepa- 
 rations, and partly left them too long in the acid. 
 
 When section preparations have lain in the solution twelve hours, and are then 
 put into nitric acid, they lose their black-blue color in a few seconds and take 
 a greenish-blue appearance. If they are then put into distilled water, the tone 
 of the color changrs directly. It becomes again noticeably darker and changes 
 into blue, with a bit of violet. The nitric acid, therefore, has left a c'Joring 
 matter in the preparation, which is insoluble in water, and in connection ■^i'.li 
 water takes a darker tone. That this remainder of coloring matter is not easily 
 soluble, even in nitric acid, can be easily shown. If the section be again dipped 
 into the acid, their color will again become greenish-blue, but not paler than in 
 the first treatment with the acid, and if washed again with water, they will again 
 take the former dark coloring. I conclude from this that a longer remaining of 
 the preparations in the acid is of no value for their further uncoloring, and 1, ave 
 them therefore, only a few seconds, at the highest half a minute in the same. On 
 the contrary, I have found that the coloring matter m the preparations remain- 
 
12 ETIOLOGY OF TUBERCULOSIS. 
 
 ing unaffected by nitric acid, is soluble in alcohol from sixty to seventy per cent, 
 if the preparations are put immediately from the acid into the alcohol. A longer 
 remaining of the preparations in alcohol appears to make the coloring matter 
 finally insoluble also for alcohol, and it is therefore to the purpose not to wash 
 the preparations in water after their treatment with nitric acid, but to place them 
 directly into the alcohol. 
 
 ' The method of uncoloring followed by me is as follows : By the help of a 
 platinum wire, which is melted into a little glass staff, the preparations are lifted 
 out of the color-solution and laid into nitric acid diluted with three to four parts 
 of water. In this they arc moved back and forth for some seconds, until they 
 have taken a greenish blue color, and are then put directly into a vessel with 60 
 per cent, alcohol. In the alcohol they remain only about ten to fifteen minutes, 
 after which they receive the after-coloring now to be described. 
 
 In preparations treated with nitric acid and alcohol the component parts of 
 the tissue are wholly colorless, or possess only a slight bluish tone of color, while 
 the tuberculous bacilli have retained an intense blue color. Relative posi- 
 tions of the bacilli to their surroundings, are, owing to the nature of the prepar- 
 ations, difBcult of proof. It is also very difficult to find single bacilli in the 
 tissue, whoso structure is made as good as completely invisible by the peculiar 
 method of illumination, which will be described later, and for this cause it is 
 necessary to give to the tissues a coloring of the nucleus. In order to obtain as 
 striking a contrast as possible, between the coloring of the bacilli and the cell- 
 grains, a yellow or light brown is chosen for the supplementary coloring material, 
 when the bacilli are blue ; a green or blue is chosen when they are red. For the 
 first case vesuvian is best adapted, for the second methyline blue. Both coloring 
 materials must nevertheless be used only in weak solutions, and not for too long 
 a time, in order that just sufficient coloring of the grains may be obtained, lest 
 single bacilli be hidden by too darkly dyed masses of grains. I use for the sec- 
 ond coloring a watery, freshly filtered vesuvian-solution, which to a depth of 3 
 ccm. is just barely transparent. On this the uncolored covering-glass preparations 
 arc so laid that they float with the prepared section downwards. Section prepar- 
 ations remain m it some minutes. It is not necessary that the section prepara- 
 tions, when they are brought from the alcohol into the vesuvian solution, should 
 bo completely colorless, because they must later be again treated with alcohol, in 
 order to get rid of the water in them, and will then lose whatever blue coloring 
 matter will have remained. 
 
 One takes the preparations out of the vesuvian solution and puts them again 
 into ten per cent alcohol and out of this into absolute alcohol. The further treat- 
 ment IS the familiar one, only it is to be recommended that for brightening the 
 preparation, instead of oil of cloves, oil of turpentine, or still better, ccdar-oil be 
 used, as these do not draw the aniline out of the preparations. With reference 
 to enclosing them with Canada balsam, I would say that a balsam diluted with 
 oil of turpentine appears to be the best adapted. Very thick balsam, which must 
 be warmed in order to enclose the preparation, must not be used, because in 
 warming, the tuberculous bacilli usually lose their color quickly. 
 
 Covering glass prepprations can be examined immediately after the washing 
 off of the vesuvian soluuon with water, or they can be dried again and enclosed 
 
ETIOLOGY OF* T0BEECaLOSIS. 18 
 
 in Canada balsam. For the examination of tlie sputum witli reference to tuber- 
 culous bacilli, the second coloring can as a rule be omitted, so that the microsco- 
 pic examination of such sputum preparation follows immediately upon the 
 treatment of the same with nitric acid and alcohol. 
 
 For the sake of a general view, I will recapitulate briefly the whole coloring 
 process : covering glass preparations dried m the thinnest possible section, after 
 the drying, three times heated in the flame ; section preparations of objects, 
 which are well hardened m alcohol ; coloring of a solution consisting of 100 com. 
 of aniline water, 11 com. of alcoholic methyl violet solution or fuchsine, 10 
 ccm. of absolute alcohol ; the preparations remain in the color solution at least 
 twelve hours (the coloring of the covering glasses can be shortened by warm- 
 ing of the solution) : treatment of the preparations with diluted (1:3) nitric acid 
 for some seconds ; washing in 60 per cent, alcohol for several minutes ; (for cov- 
 ering glasses, moving back and forth in alcohol several times is sufficient) ; second 
 coloring in diluted vesuvian solution or methyline blue for several minutes ; wash- 
 ing again in 60 per cent, alcohol, getting rid of water by means of absolute 
 alcohol, brightening in cedar oil ; microscopic examination of the preparation ; 
 enclosing of the preparation in Canada balsam if the same is to be preserved. 
 
 As to the microscopic examination of the objects prepared m this manner, 
 all that I have saidin other works* about objects colored for the microscope, holds 
 true also for these. In this case also structural relations, which make themselves 
 manifest by the varying refractive power of the single parts of the tissue, are not 
 to be settled ; it concerns us only to see the various color relations of the micro- 
 scopic objects, that is to say, representations of absorption, as clearly and sharply 
 as possible. The structural image whose effect is only disturbing must therefore 
 be gotten rid of, which, as I have shown, can be done most completely with the 
 help of the well-known illuminating apparatus of Abbe. The peculiar illumina- 
 tion which this apparatus affords whenit is used without " abblendung," cannot be 
 borne by all systems of lenses. The last must be constructed with special refer- 
 ence to this method of illumination. The greater an opening angle a system 
 possesses, the better it is adapted for the observation of the images of absorption, 
 with help of Abbe's illuminating apparatus. For this reason oil-immersion sys- 
 tems can accomplish the most in the investigation of colored objects. 
 
 The covering-glass prepaiations, if rightly prepared, must possess so little 
 thickness that the structure ;s formed of a single layer of objects, and in and of 
 itself is little to be considered. These preparations can on this account be exam- 
 ined simply in water and in case of need, a system of water-immersion is sufficient 
 for them, if the field of vision be suflBciently brightened by a condenser. In the 
 case of section-preparations, it is, on the contrary, impossible to set aside the 
 structure formed by so many layers of tissue one above the other, unless the prep- 
 aration is laid in a liquid which has high power of refraction. It is necessary 
 to do away with the differences in refraction of the tissue, and to use the full 
 illuminating power of Abbe's apparatus, and must use its full power to the best 
 advantage through the large opening angle of an oil-system. One may easily con- 
 
 *Uiitersucliuiigeii ueber dis Aetiologie der Wundinfectiouskranklieiteii. Leipzig 1878, 
 p. 31, etc. 
 
 Mittlieilunengen aua dem Kaiserlictien GesundlieltBainte. 1E81, Vol. 1, p. 9. 
 
14 .ETIOLOGY OF TUBEBCL'LOSIS. 
 
 viDce himself of the necessity of the optic helps here described as absolutely 
 necessary, if one first examines a properly colored section in -water and examines 
 it microscopically by a dry system or a water-immersion system and a compara- 
 tively narrow " blendi " (blind or opening). Fine distinctions of color, and 
 small colored bacteria in tissues, which are to any extent rich in grains, can under 
 these conditions Ecarcely be distinguish( d. Also placing the section in glycerine 
 changes almost nothing, because the differences in refraction of the parts of the 
 tissue are equalized much too slowly and insutBciently. A noticeable improve- 
 mrnt is gaimd by brightening the preparation by means of highly refractive 
 liquids, such as oil of cloves, oil of cedar, etc.; for the brightening rests tipon the 
 snore or less thorough destruction of the structure-image. But even this improve- 
 ment is not sufficient to allow the color-pictures to appear iu full clearness and 
 sharpness. Only the quantity of light pouring in from all sides by means of 
 Abbe's illuminating apparatus and the od-system can fulfill this task. Who only 
 cares to examine covering-glass preparations, without caring for complete cer- 
 tainty with regard to the state of things, for him a microscope with water- 
 immersion system and without illuminating apparatus, will in case of need prove 
 itself suflScient. Dry systems are not to be used for bacteria investigati ns. As 
 soon as reliable investigations of finer bacteria are to be undertaken, or if one 
 wishes to gain an independent judgment as to the newer results of bacteria re- 
 search, it is absolutely necessary to have at hand the very best optic helps, that 
 is to say oil-immersion systems and Abbe's illuminating apparatus. With regard 
 to the magnifying powers which must be used for the examination of tubercu- 
 lous bacilli, I will remark that 500-700 fold magnifying power is most to the 
 purpose, and that this is best reached with an oil system -jV of an inch and the 
 corresponding oculars. 
 
 In the practical use of the coloring processes just described, the component 
 parts of the tissue of the body conduct themselves almost without exception dif- 
 ferently from the tuberculous bacilli. While the latter, in spite of the treatment 
 with nitric acid, alcohol and vcsuvian, keeps the dark blue color which they have 
 taken, the remaining animal tissues, as already mentioned, lose the Kuo color again, 
 and in the second coloring the grains of the cells as well as the products of destruc- 
 tion of the latter, further the little grains of the plasma-cells are dyed brown. 
 Only some parts of the tissue make an exception, as hair and epidermis, 
 wtiich remain more or less blue-colored. Since in these last tuberculous bacilli 
 are hardly to be sought for, the finding cf bacilli in the tissues is made exceedingly 
 easy, by their characteristic conduct towards aniline coloring matters. Even in 
 the closest masses of grains and in the midst of broken down cells, which often 
 take all possible forms, from the smallest little points and micrococci-like forms, 
 to the longish staff-like forms, one can with absolute certainty distinguish 
 single tuberculous bacilli from these closely similar forms by means of 
 their dark blue color, which in the brown-colored surrounding and owing 
 to (he light-absorbing power of the brown ground appear as staffs almost 
 colored black. This noticeable difference in the color-reaction holds nevertheless, 
 as must constantly be repeated, only for the method of coloring described 
 here. A different preparation of the objects than the quick and good al- 
 cohol hardening of the organs, made the condition here, apoears to bring about 
 
^tioJdgy of tubeeculosis. 15 
 
 other relations. For while usually the little grains of the plasma-cells conduct 
 themselves like the cell-grains and show a different coloring from the tuberculous 
 bacilli, I have lately seen a preparation, made by Dr. Benda's assistant in the 
 pathological institute in GEittingen, in which tuberculous bacilli were not to be 
 found, but on the contrary the grams of the plasma-cells showed themselves colored 
 blue. Probably in this case the object from which the section was prepared had 
 received a treatment with cromic acid or had not been hardened quickly enough 
 in alcohol. 
 
 Accident comes to our help in proving the existence of tuberculousbacilli, since 
 not alone the parts of the tissue lake a different coloring, but also all other bacteria 
 which I have known until now and examined, with the exception of the Icpra- 
 bacilli to be mentioned later, also react in an opposite manner from the tuberculous 
 bacilli under Ehrlich's method of coloring. Bacteria coming from the mouth are 
 almost always to be found in phtisic sputum. I have never seen that one of 
 these numerous sorts of bacteria showed the same color-reaction as the tuberculous 
 bacilli. This observation has been confirmed by many reliable investigations, and 
 can be considered as an established fact. The same is true of the tuberculous 
 bacilli occurring in the contents of the intestines, when tuberculous ulcers are 
 present. When this sort of discharge is prepared and colored in the prescribed 
 manner on the covering glass, it appears to consist almost wholly of bacteria; 
 they fill the layer in such thick masses. But without exception they take a dif- 
 ferent color from the tuberculous bacilli, and especially is this the case in the smaller 
 sorts of bacilli, which might perhaps lead one to mistake them for. A peculiar 
 behavior is shown by a large sort of bacilli, which form somewhat large, oval 
 spores standing on ends, in that the spores often keep a plainly manifest, some- 
 times indeed an intense blue color, while the substance of the bacillus is itself dyed 
 brown. According to all appearance these spores only take the color a short time 
 after their formation, but remain uncolored after they are older. Among the 
 many spores of the contents of the intestines which belong to other sorts of bacilli, 
 until now none have been found which took the color of the tuberculous bacilli. 
 Also the spores of the inflammation-of-the-spleen bacilli, hay bacilli and others, 
 which Dr. Gaffke examined at my instance with reference to this color-reaction, 
 remained uncolored. On the contrary Dr. Gaffke found during these investigations 
 that the spores of ' ' shimmel-pilzc " take a strong blue. Also a certain kind of yeast 
 seems to take the color. Since a mistaking of tuberculous bacilli for the above 
 mentioned spores and yeast is impossible, their diagnosis so far as it rests upon 
 the color-reaction is not thereby prejudiced. 
 
 Of late I have examined many sorts of bacteria-bearing substances, such as 
 decaying meat infusion, decomposing urine, blood milk, vegetable infusion, mire 
 from swamps with Ehrlich's coloring method, but have never found bacteria 
 which take the same color-reaction as the tuberculous bacilli. I must therefore 
 consider all claims for the appearance of bacteria which conduct themselves in 
 regard to color exactly like the tuberculous bacilli, and which are said to be found 
 in sputum, decaying liquids, the contents of the intestines in healthy men and in 
 swamp-mud, for mistakes and resting upon an erroneous use of the coloring 
 method. I feel myself so much the more justified in this opinion since I almost 
 daily see examples of the difficulties which the use of this certainly rather com- 
 plicated color technique oilers to most people. 
 
1^ Etiology ob' TaBEEC^tosis. 
 
 Asidefrom the tuberculous bacilli, until now only one sort of bacteria has 
 been known which takes color in the same way as the tuberculous bacilli ; these 
 are, as I have already mentioned in my first communication, the Icpra-baciUi. 
 This fact is so much the more worthy of notice, since not only the parasites belong- 
 in;: to tuberculosis and to lepra arc similar in many ways and plainly nearly related, 
 but, as ii well known, those two diseases stand very near to each other anatom- 
 ically ns well as setiologically. To be sure, the coloring propertiesof the two sorts 
 of bacilli are not identical. For although the lepra-bacilli can be colored by the 
 fame process as the tuberculous bacilli, the opposite is not the case. The first 
 take, as is well known and as Neisser first proved, the nucleus-coloring of Weigert, 
 which the last do not. However similar the two bacilli are in figure, size, &c., 
 as soon as it comes to a diagnostic distmction, it becomes easy to recognize them 
 through their different response to Weigert's nucleus coloring. 
 
 The example of the lepra-bacilli already teaches that the tuberculous bacilli 
 occupy in no way an entirely exceptional position in regard to their response to 
 coloring matters ; it is therefore not improbable that in course of time other sorts 
 of bacteria will be found, which possess the same or similar coloring properties 
 as the tuberculous bacilli. But any influence on the apprehension of the astiolog- 
 ical importance of the tuberculous bacilli would not be exercised by such a discovery. 
 For the special reaction against coloring matters is nevertheless not the only 
 specific property of the tuberculous bacilli. They possess, as we shall see later 
 also in biological relations, a number of other peculiarities, which give still more 
 weighty reasons for separating them from the known bacteria as a specific sort. 
 
 In all such considerations it is very much to the point to bring to remembrance 
 how the same relations exist in inflammation of the spleen. One will then see 
 that inflammation-of-the-spleen bacilli possess no specific coloring qualities and 
 nevertheless, as is universally acknowledged, are bacteria of a distinct kind and 
 form the cause of inflammation of the spleen. Exactly the same might be the 
 case with tuberculous bacilli if they did not accidentally distinguish themselves 
 from other bacteria by color-reaction. If the latter is nevertheless a fact, it is cer- 
 tainly of value in diagnosis, but it is a great error to think that with the specific 
 color-reaction of the tuberculous bacilli, their {Etiological importance stands and 
 falls. 
 
 Further it appears to me not improbable that in the near future still further 
 methods may be found by means of which tuberculous bacilli can be colored. 
 •Elirlich's coloring method has already experienced many modifications, of which 
 theoretically the most worthy of notice is the fact found by Ziehl, that anihne can 
 be replaced by other substances, such as phenol, — C|.H4(OH)2 — resorcine, &c. 
 Tlie statements of some authors, that the tuberculous bacilli may be dyed with 
 pure fuchsine appear to hint that still other ways exist .n which the coloring can 
 KQceced. The diagnostic importance of Ehrlich's method, even if other methods 
 which have no exclusive character are found, suffers by no means. For that 
 remains in spite of all a well established fact, that by strict following of Ehrlich's 
 method the tuberculous bacilli conduct themselves in a manner wholly peculiar 
 to them and are thereby to be distinguished from all till now known bacteria. 
 The method has the value of a chemic reaction, which has made possible the dis- 
 tinction of substances difiieult to divide, nevertheless only under the condition 
 
^ETIOLOGY OF TUBEECtTLOSIS. 17 
 
 that it be used exactly according to tlie given directions. It would be of special 
 interest to be able to give the bacilli a brown or yellow coloring, because only 
 under this condition would it be possible to get usable photographs of the tubercu- 
 lous bacilli. Of late I have, to be sure, succeeded, with the help of a previously 
 given treatment of the preparations, with a very weak solution of kali (j^^ p. M ) 
 to color the tuberculous bacilli a quite intense brown, nevertheless the preparations 
 do not meet the demands required for photography. It ia to be hoped that this 
 difficulty will be overcome. But for the present I have been obliged to do with- 
 out photographs, however much I have wished by means of photographs to render 
 possible a reliable comparison between the form and size of tuberculous bacilU 
 and other similar ones. 
 
 As another hindrance in the coloring of the tuberculous bacilli the temporary 
 character of the coloring must be mentioned. After a shorter or longer time in the 
 preparations enclosed with Canada balsam, the color of the bacilli begins to lose 
 its intensity, very gradually it becomes less noticeable and finally vanishes 
 completely. The preparations colored wi*h methyl-violet and gentian violet 
 pale most quickly, for in some cases the color of such bacilli vanished in two days. 
 The preparations colored with fuchsiue keep much longer, as do those colored 
 with alkaline methyline blue solution. Why it is that the color is so fleetmg, 
 wh'le the same color in the dyeing of other bacteria have proved themselves un- 
 changeable for years, I am not able to say. But from the circumstance, that in a 
 great number of prepared specimens single ones have been found which have 
 preserved the color completely unchanged for almost a year, I must conclude, that 
 some sort of conditions are present and may be found, which will make possible 
 the retaining of the color. 
 
 Moreover the preparations which are so pale have not become entirely useless, 
 as with little trouble they can be colored again. The Canada balsam must be 
 liquified by heat, the specimen taken off carefully with a pinsel and put into oil of 
 turpentine. After 24 hours it is laid in absolute alcohol and after another 24 hours 
 into the color solution to go through the whole coloring process again. The tu- 
 berculous bacilli take the blue color just as intensely as at first, but their surround- 
 ings, on the contrary, appear less beautifully and clearly colored than before. 
 
 A reliable explanation of the difference between tuberculous bacilli and other 
 bacteria in their action in regard to coloring matters appears to me impossible for 
 the present, on account of the insufficient knowledge of the more delicate structure 
 of the chemical constitution. On many grounds it seems likely that the tuber- 
 culous bacilli are surrounded by a coating, which acts differently toward coloring 
 matter than the contents, as we already know to be the case with other bacilli. 
 The bacilli dyed with methylme blue appeared thinner than those dyed with 
 methyl violet or fuchsine. One sees in the group : in which the bacilli lie closely 
 pressed together, that the methyl violet colored bacilli move, and the bacilli dyed 
 with methyline blue and appear thin, are separated from each other by plainly 
 manifest spaces. Further, the coloring of the bacilli intensely dyed with methyl 
 violet in growing pale does not vanish uniformly, but an outer layer grows pale 
 first, so that of the thick bacillus a thinner, still intensely thread remains, which 
 possesses about the thickness of the bacillus colored with methyline blue. Finally 
 the firm cleaving together of the bacilli in the groups also speaks for the presence 
 
18 Etiology ov TurBEECtJLOsie. 
 
 of an enwrapping substance which joins them. It is therefore thinkable, that a 
 coating exists, possessed with special properties, and enwrapping the bacilli, and 
 that this allows the entrance of coloring matters under the simultaneous influence of 
 alkali aniline and similar matters, but is on the contrary more or less impenetrable 
 for acids. But in the face of the facts now known, one cannot go farther than to 
 conjectures. 
 
 If I now go over to the description of the tuberculous bacilli themselves, although 
 they were first made visible by the help of coloring matters, it appears nevertheless 
 to the point, first to describe their properties as they make themselves known in a 
 living condition and without being influenced by any sort of reagents. To get 
 preparations for this sort of observation, only such tuberculous substances can be 
 used as contain considerable masses of bacilli, because single bacilli cannot be distin- 
 guished with certainty in the masses of detritus without help of the color reac- 
 tion. For this purpose I have used little tuberculous knots from the lungs of 
 guinea pigs, after I had convinced myself by coloring of the great quantity of 
 tuberculous bacilli in them ; the little knots were crushed in a drop of blood 
 serum free from bacteria, the substance spread about as finely as possible in the 
 liquid, a drop of this liquid sufficiently large for microscopic examination spread 
 out flat on the under side of a covering-glass and fastened with vasiline on to a 
 hollow object-holder, in order to avoid disturbing currents in the liquid and a too 
 quick evaporation. In a preparation prepared in this manner, in the microscopic 
 examination conducted in the usual manner, that is to say in a suitable "ab- 
 blendung" of the light by diaphragms, there are found among opaque heaps of in- 
 determinable nuclei, brighter spots in which the formed elements lie less thickly, 
 and here one notices numerous colorless, very fine and short little staffs. The 
 same are mostly united in small groups ; in those which lie singly aside from the 
 so-called molecular motion, no motion of their own is to be noticed. The length 
 of the little staffs is about from one-quarter to one-half of the diameter of a red 
 blood corpuscle. An organization is not be noticed in them, and one cannot re- 
 organize their relations to the surrounding cells in this sort of examination, and 
 if no farther observations could be made, one would rather believe he had some 
 sort of lifeless forms before him than bacteria. 
 
 If such a covering-glass be lifted up from the concave object-holder, so that > 
 the bacilli-bearing substance be dried and then doubly dyed in the maimer already 
 described, then the numerous grains and remains of cells appear dyed brown, 
 the little staffs on the contrary receive an intense blue coloring and distinguish 
 themselves sharply from all known component parts of the animal tissue with 
 which they are mixed. The bacilli do not show themselves in their full number 
 until after their coloring ; they may be distinguished not only on the thinnest 
 spots of the preparation, but everywhere with full certainty, even among the 
 thick heaps of cells. It is noticeable that the little staffs appear thinner after 
 the coloring than in the uncolored condition, the reason for which is, that be- 
 fore the coloring they must be observed by light cut off by diaphragms, in which 
 case the lines of interference on the borders of the object appear to enlarge its 
 diameter, while the observation of the colored bacilli is made in full light falling 
 upon it from all sides, through which all phenomena of interference are ex- 
 cluded. 
 
ETIOLOGY OK T0BEKCU.LOSI8. l9 
 
 In like manner one can examine the most various objects by spreading out 
 the substance to be examined as to its contents of tuberculous bacilli on the cov- 
 ering-glass and by coloring the snme. Nevertheless, one does not learn much 
 more than that the bacilli are present in a tissue or in a liquid and in what quan- 
 tity they are present. Their position and their relations to the surrounding tis- 
 sues cannot, in this way at least, be determined. The examination on the cover- 
 ing-glass is therefore sufficient for liquids, but for tissues can only have a pre- 
 liminary, provisional character. Only the examination of the prepared sections 
 of hardened parts can give reliable information as to the presence and diffusion of 
 bacilli in the tuberculously altered organs. 
 
 To find out whether bacilli are regular accompaniments of tuberculosis, I have 
 examined as extensive a ground as possible. Materials for this investigation I 
 have received for the most part from Dr. Friedlaender, who, at my request, and in 
 the most gbliging manner, made the rich material of the city hospital in Friedrichs- 
 ham accessible to me, and from the director of the city hospital in Moabit, Dr. 
 Guttman, who committed to my charge a number of cases of tuberculosis for ex- 
 amination. It is a pleasant duty in this place to thanli both gentlemen for the 
 help they have given to my work. 
 
 In the following description of the results gained in these investigations I must, 
 in order to make a general survey, omit the historical enumeration of the single 
 cases in the order in which accident placed them in my hand, and will speak of 
 them as grouped according to the usual anatomic points of view. Before I turn 
 to this, however, I must make a few general remarks. When a little tuberculous 
 knot is examined in prepared sections, without the use of nucleus-coloriag, and 
 without the diffused light of Abbe's illuminating apparatus, it appears like a body 
 formed of cellular elements thickly crowded together and therefore only slightly 
 transparent. As soon as the little tuberculous knot becomes caseous in the centre 
 the cells change into a more or less fine grained, almost opaque mass, in which 
 fine details are not to be distinguished. But a thoroughly different image of the 
 tubercle is gained when the prepared sections are laid into strongly refractive 
 media and the examination is undertaken after tlie nucleus-coloring, and by dif- 
 fused illumination. The youngest tuberculous knots then show themselves to 
 consist of colored grains heaped together. Nevertheless the grains are not so closely 
 packed but that a section of ordinary thickness appears transparent enough to 
 make it possible to distinguish the most delicate form elements occurring in the 
 space between the grains. The caseous centres of the tuberculous knots in the 
 prepared section appear wholly changed ; they appear almost uncolored and com- 
 pletely transparent because there the cells have died and take no coloring ; only 
 here and there in thrai are f ovmd the remains of nuclei going to pieces, in the form 
 of colored grain groups which, to be sure, are pretty closely pressed together but 
 still allow all single form elements to be distinguished. Larger caseous herds 
 conduct themselves in the same manner. The caseous substance itself has become 
 completely transparent by the treatment and shows only a light greyish-yellow 
 color tone interrupted by single brown grains or groups of grains. Every single 
 tuberculous bacillus- can be distinguished with ease. The conceptions of the mi- 
 croscopic image of the tubercle and of the tuberculously altered tissue which usually 
 obtain are to be modified according to the circumstances just described when the 
 
20 JETIOLOG-Y OF TUBEECULOSIS. 
 
 examination of the pictorial reproduction of prepared specimens witli nucleus- 
 coloring and illuminated by difEused light is concerned. 
 
 As to the qualities of tuberculous bacilli in general, as they manifest themselves 
 in the colored condition, the following is still to be mentioned. 
 
 They always appear in the form of little staves whose length, as has already 
 been given in the description of uncolored bacilli, is equal to ^— J of the diameter 
 of a red blood corpuscle (about 0,0015—0,0035 mm). The diameter of the thick- 
 ness is as constant as the length of the bacilli is variable, provided that one and 
 the same coloring method is used. Under the coloring method first used by me, 
 with alkaline methyline blue solution, they appear considerably thinner than with 
 the use of Ehrlich's method. It is difficult to fix the slight size relations about 
 which we are here concerned without the use of photography. When I look 
 through a considerable number of my bacteria photographs for bacilli which cor- 
 respond best as to size with tuberculous bacilli, I find in F. Cohn's " Beitrage zur 
 Biologic der Pflanzeu ," II Vol., 3 Book, in the photographs given in Plate 15, No 
 1, among club-shaped bacilli with spores fixed in their ends, very thin and small 
 bacilli which, if magnified 700 instead of 500 times as in the photograph, would 
 come nearest to the tuberculous bacilli. There are among these bacilli also some 
 which are spore-bearing and which about give a representation of the spore-bear- 
 ing bacilli to be mentioned later. Also in the bacilli taken from blood putrefaction 
 In mice (Miiuse septiciimie) and shown in this work, Vol. I, Plate VII, Fig. 41, are 
 bacilli almost as thick, but on the average somewhat shorter than tuberculous 
 bacilli. 
 
 The tuberculous are usually not completely straight little staves ; one usually 
 finds slight breaks or bends and sometimes a crookedness which in the longest 
 specimens goes so far as to suggest screwshaped windings. By this varying from 
 the straight-lined forms the tuberculous bacilli distinguish themselves from other 
 bacteria which come noticeably near them in size relations according to the photo- 
 graphs. 
 
 The distribution of the bacilli in the tuberculously-altered tissue is a very 
 varying one. Sometimes they are heaped together in dense masses, so that by a 
 very slight magnifying power bacilli-bearing spots can be recognized by their blue 
 color. Very frequently, however, they are present only in small numbers. One 
 finds the bacilli with most certainty where the tuberculous process is just beginning 
 or is m a state of rapid growth. Here they are to be found in moderate numbers 
 and between the nuclei of the cells which are heaped together and which usually 
 show the epithelioid character at an early stage. After a more careful observation 
 it is manifest that a bacillus almost always lies close beside a nucleus, and that It 
 is to be found in the interior of the cell belonging to this nucleus. One cell can 
 often contain two or even three bacilli. In places where the disease has made 
 greater progress the number of bacilli usually increases extraordinarily. They 
 then often group themselves into little heaps closely pressed together, in which the 
 bacilli lie parallel and are connected, so closely that it is often difficult to recognize 
 thefact that the group is composed of single bacilli. In this arrangement thetuber- 
 culous bacill i bear a great resemblance to the lepra bacilli , which are mostly grouped 
 in this manner. The relation of the tuberculous bacilli to the cells cannot be de- 
 cided in this stage, because the cells have already experienced groat changes and 
 
jrnOLOGV OF TUBERC0LOBIS. 21 
 
 are in process of dying. Tlieir nuclei begin to decompose and to change themselves 
 into irregularly formed grains of very varying size. Gradually these become scarcer 
 and there remains a uniform mass which will not take nucleus coloring and in 
 which all the cells originally present have died. This mass forms what was 
 formerly considered the essential part of the tubercle, as the bearer of the infectious 
 material, namely, the caseous centre of the same. But, as a rule, this caseous 
 substance is very poor in tuberculous bacilli. Only when the death of the 
 cells and their change into the nucleusless caseous mass has taken place very 
 quickly are the bacilli visible for a time in considerable numbers. It is plain that 
 they retain the capacity of fixing the coloring matter longer than the cells perish- 
 ing under their influence. But very soon the bacilli themselves undergo farther 
 changes, either dying or go into the stage of spore formation, in which they gradu- 
 ally lose their power of taking color. In the last case only their spores remain in 
 the caseous substance, and as until now no means have been found of coloring the 
 spores of tuberculi m any way whatever, their presence after the vanishing of the 
 tuberculi betrays .tself only by the infectious qualities of the caseous substance in 
 which they are imbedded. On account of the importance, formerly and even very 
 lately, erroneously attached to the caseous products of the tuberculous process, it 
 may not be superfluous emphatically to direct attention to the facts that in all 
 tuberculous affections the tuberculi appear first, collections of cells joining them- 
 selves to these ; and that the dying of these cells and the caseous change resulting 
 from this are secondary processes.* 
 
 The opinion which still, to a great extent, holds ground that the relation 
 between the bacilli and the caseous degeneration is the opposite of this, that the 
 becoming caseous represent the primary, and that by means of this a suita- 
 ble breeding ground is prepared for the tuberculous bacilli, is therefore com- 
 pletely erroneous. For the anatomical comprehension of the tissue changes in 
 consequence of tuberculosis the process of becoming caseous may be of interest, 
 but for the aetiology of tuberculosis it has not the slightest importance. 
 
 If I have lately been charged with paying too little attention to the process 
 of caseous degeneration in my account of the aetiology of tuberculosis, the 
 charge is unfounded, for it rests upon a misunderstanding of my standpoint, since 
 I have only treated the etiological relations of tuberculosis, but have left the 
 pathological details to the pathological anatomists, especially when they lie so 
 far aside from aetiology as the caseous changes of the tuberculous tissue. 
 
 Of greater importance for the questions interesting us here are the relations 
 of tuberculous bacilli to the gigantic cells so frequently appearing in tubercu- 
 lously altered tissues. 
 
 These peculiar formations are so frequent in tuberculous tissues that it was 
 for a time believed that they must be considered as characteristic of tuberculosis. 
 Since the gigantic cells are almost always situated at the centre of the little tuber- 
 culous knot, the opinion has often been expressed that the tuberculous virus 
 must be contained in their interior — has indeed been pointed out in the shape 
 of very small grains. 
 
 * Baumgarten, " TJeber die Wege der tuberkWosen'Inf action. " Zeitsohrift £. klin. Med. 
 Bd. VI, heft. I. 
 
22 J5TIOLOGT OF TUBEECUL0ST8. 
 
 It has now been shown to be certain that the gigantic cells occur in other 
 disease processes and are not specific products of tuberculosis. Nevertheless the 
 conviction that the infectious material must be contained in the gigantic cells has 
 proved itself correct. For as soon as gigantic cells appear in the tubercles, tuber- 
 culous bacilli are almost regularly found in them, and the relation of bacilli to 
 gigantic cells is a manifold one. 
 
 In all slowly developing tuberculous processes, for example scrofula, spongy 
 inflammation of the joints, etc., in which the bacilli are present only in scanty 
 numbers, we find the bacilli almost exclusively in gigantic cells, and then always 
 only one or at most a few specimens in each cell. But when, corresponding with 
 the more or less intensive course of the process, the bacilli appear in considerable 
 numbers, then the gigantic cells which may be present are more generously sup- 
 plied with them, and the number of bacilli enclosed by a gigantic cell may reach 
 fifty or more. 
 
 A single bacillus in the interior of a gigantic cell is sometimes not easily rec- 
 ognized, for it often happens that the little staff may not be in the horizontal 
 plane of the prepared section, but is placed diagonally or perpendicularly, and 
 then appears in the microscopic image not as a blue line but only as a point, 
 which can only be traced to a certain distance and its staff form recognized by 
 raising and lowering the tube. Since the contents of the giant cell take a 
 more or less brown-color tone, the little staff does not always show itself In the 
 characteristic blue, but in a darker, almost black color, the reason being that ani- 
 line brown absorbs the blue part of the spectrum, and therefore a blue object 
 observed through a brown solution, must appear black. Attention should, by 
 this opportunity, be given to the fact that bacilli never look blue but always black 
 when the ground on which they are seen is brown, when, for example brown- 
 colored nuclei lie under them. 
 
 Although, as already said, it may sometimes be diflBcult to find a single bacil- 
 lus in a gigantic cell, bacilli which in considerable masses fill a giant cell give a 
 so much the more striking picture, which cannot be overlooked, even by a weak 
 magnifying power. In this case the giant cells appear like little blue circles 
 which are surrounded by a brown wall, the nuclei of the giant cell. 
 
 The arrangement of the bacilli in the giant cells often takes a very peculiar 
 form. When the nuclei of the giant cell form a closed ring, and, for example, 
 only one bacillus is found within it, the same generally lies in the centre or at 
 least only a little excentric. 
 
 The nuclei of the giant cell are often forced toward one end, that is in a uni- 
 polaric arrangement, especially if the cell possesses an oval figure, or one even 
 longer in proportion to its width. In this case the bacillus is usually found in the 
 part of the cell free from nuclei ; it often takes a position exactly opposite to 
 them, and lies in the extreme point of the nucleus free pole. In the observation 
 of the giant cells the supposition involuntari'y forces itself upon one that a sort 
 of antagonism exists between the nuclei of the giant cell and the parasite enclosed 
 by it, which effects the greatest possible distance between the nuclei and the 
 bacilli. This remarkable opposition between nuclei and bacilli is most noticeable 
 in those giant cells whose nuclei are grouped equatorially and which then a 
 bacillus in each of the nucleus, free poles, or by a bipolar arrangement of the 
 
^riOLOGY OF T0BEBCULOSIS. 23 
 
 nuclei In ■which, each heap of nuclei holds a bacillus as it were in check. 
 
 Also ■where larger numbers of bacilli are observed in giant cells the opposi- 
 tional grouping of nuclei and bacilli can be noticed. Usually, however, an 
 entirely different arrangement of bacilli occurs. It looks as if ■with increasing 
 numbers the behavior of the bacilli towards the nuclei became more active. 
 They force themselves, namely, more and more towards the periphery of the 
 cell, squeeze themselves between- the nuclei and finally break through the wall 
 of the nuclei. 
 
 During this process it is very worthy of notice that the bacilli, in this case, 
 regularly place themselves with their axis perpendicular to the surface of the 
 giant cell, so that in a microscopic image if the upper curvature or the base of 
 the gigantic cell be shown, they appear as points ; when, on the contrary, the 
 greatest diameter of the cell is show, we get the image of a circle of rays formed 
 of blue staffs. 
 
 Such a great increase in tlie number of bacilli appears regularly to be fol- 
 lowed by the destruction of tlie giant cell ; for in the neighborhood of giant cells 
 supplied with radiately arranged bacilli, especially towards the interior of the 
 ' tuberculous herds, one often finds groups of bacilli which show the radiate 
 arrangement, but are no longer enclosed by brown-colored nuclei. Moreover, 
 since many transitional forms are found, it cannot be doubted that such radiated 
 groups of bacilli mark places in which giant cells were formerly found whose 
 nuclei have vanished, and of whose contents only the bacilli remain. 
 
 By the help of the microscopic images just described one can read about 
 the following conception of the relations of bacilli to tlie cell contents of the 
 tubercle without losing oneself in too venturesome hypotheses. The first stage in 
 the development of the tubercle is the appearance of one or more bacilli in the 
 interior of cells which bear an epithelioid character. How the bacilli get there 
 can scarcely be explained, otherwise than that they are taken up from already 
 existing tuberculous herds and carried along by such tissue elements as possess 
 motion of their own, that is to say, by wandering cells, be they in the blood, the 
 lymph, or in the tissue itself, for the bacilli possess no motion of their own. 
 Only so is the peculiar fact to be explained that frequently single bacilli or little 
 groups of the same are found dispersed at quite uniform and comparatively great 
 distances from each other, as, for example, in scrophulosis, fungous and lupous 
 tissues and in general in all chronic tuberculous affections. For a wandering 
 cell which has taken up a bacillus takes therewith no such harmless burden as if it 
 swallowed a grain of cinnabar, a particle of coal or other indifferent material. 
 Laden with ihe latter it can still go oyer much ground, but under the deleteiious 
 influence of the bacillus changes occur in the wandering cell which soon bring it 
 to a standstill. Whether the wandering cell perishes, and the bacilli are taken 
 up by other cells present at the spot, which last then talce an epithelioidal charac- 
 ter ; or, as appears to me more probable after my investigations, the wandering 
 cell transporting the bacillus itself changes into an epithelioid cell and after that 
 into a giant cell must be decided by studies directed to that special point. 
 
 For the assumption that the bacilli are originally carried along by wandering 
 cells, and that their dispersion in the tissue depends upon this, the following rea- 
 sons can be given : In the first place I would like to bring to remembrance an 
 
24 ^TIOLOGi' OF TUBKKCULOSIB. 
 
 analogous process in which also staff-shaped , acteria are iDCorporatcd by Ihe col- 
 orless cells of the blood. This case is the putrefaction of the blood in mice 
 (M!iuse-septicamie) described by me in the "Investigations of the JStiologyof 
 Infectious Diseases." In this disease bacilli very similar to the tuberculous bacilli 
 are to be found in the interior of the white blood corpuscles, and at first there are 
 only one or two specimens close to the nucleus ; then they increase very rapidly 
 in the cell, destroying the nucleus and finally bursting the cell in order, having 
 become free, to be again taken up by other cells and to prepare for them a rapid 
 ruin, so that in a short time the majority of the white blood corpuscles are found 
 inhabited by bacilli. The tuberculous bacilli grow, as we shall see later, very much 
 more slowly than the bacilli of septictlmie (putre. of bloodj, and the cells laden 
 with them can therefore manifest vital functions very much longer. The further 
 course of both diseases is, in accordance with this fact, very different, in spite of 
 the fact that the first beginnings of the bacteria invasion possess such great simi- 
 larity. 
 
 Direct observation also speaks in favor of the assumption that tuberculous 
 bacilli are first seized and transported by the wandering cells. This can best be 
 recognized in the cases in which considerable numbers of bacilli are introduced 
 directly into the course of the blood, for example, by injection into the ear veins 
 of the rabbit. If an animal infected in this manner be soon killed, one still finds 
 in the blood numerous white blood corpuscles which enclose one or more tuber- 
 culous bacilli, and moreover in the tissue itself of the lung, liver and spleen, 
 genuine round cells appear which are provided with a simple or divided nucleus, 
 still possess no epithelioid form, therefore exactly resemble the colorless blood 
 cells and yet contain'uberculous bacilli. Another explanation of this, other than 
 that they are wandering cells which took up the bacilli in the course of the blood 
 and transported them into the neighboring tissue, will scarcely be found Also 
 in the case of guinea pigs into whose bauchhohle (belly cavity) considerable num- 
 bers of tuberculous bacilli were injected, and which died in the course of the first 
 week, the same appearances were found. 
 
 A third ground for this assumption appears to me to lie in the fact that in 
 dead tissues, in such places, therefore, wherein the influence of the living cells upon 
 the bacilli is completely excluded, when a lively growth of the bacilli takes place, 
 they arrange themselves in typically formed groups which resemble the peculiar 
 forms of the bacteria colonies in reinculturen of the same on blood serum. 
 Wo must therefore consider these funis to be those taken by tuberculous 
 bacilli when developing undisturbed mil when their grouping is decided only 
 by the variations and changes of p! i- ■ c <:: '.itioned by their growth. Every 
 other arrangement is to be looked upi n r-t r^ wnrkingof some sort of disturbance, 
 for example, that caused by curn;:/-i ill' u liquids, or by the direct influence 
 of movable tissue elements. So t'n! i 1 itiv(! ]> sitions of the bacilli in the giant 
 cells, especially their position as o;ipocd I') t' e nucleus, and the radiating ar- 
 rangement appear to me to be eoiitr.iionrd upon currents in the plasma of the 
 cell, and not by motion belong!: g to the bacilli themselves, since the bacilli 
 after the death of the cells do nrt change the radiating arrangement once taken. 
 After the wandering cell which transported the bacillus has changed itself 
 into an epithelioid cell and given up moving from place to place, the path- 
 
^TI0r,0GY Olf TDBEEOULOSIS. 2S 
 
 ogenic influence of the bacilli prepares to spread itself out upon the neighbor! 
 iug cells existing within a certain circuit. Whether they have proceeded from 
 cells already present in this place in consequence of the attraction exercised by 
 the bacillus itself, or rather by the materials produced by it and diffused into the 
 surroundings, all cells situated within a definite region change into epithelioid 
 cells. The cell containing the bacillus suffers still greater changes. It grows 
 constantly larger, while at the same time the nuclei constantly increase, and it 
 finally attains the shape and size of the familiar giint cells. That the develop- 
 ment of the giant cells really goes on in this manner can be seen from suitably 
 prepared sections, which show all stages of development from simple epithelioid 
 cells with one bacillus to the completely developed giant cell with many nuclei 
 and many bacilli. As most suitable for the study of the development of giant 
 cells I should consider the tuberculous tissue of cattle and horses, which is espec- 
 ially rich in giant cells and in which I have often seen the above mentioned 
 transitional forms. The furtlier fate of the giant cells is a varied one, according 
 as the progress of the disease is rapid or slow. In the last case the number of 
 bacilli enclosed by a giant cell is always a limited one. Osually there are only 
 one or two. It is indeed scarcely to be thought that the bacillus found in a large 
 giant cell is the same which caused the formation of the cell. One finds not in- 
 frequently in a giant cell a bacillus which is no longer so intensely colored as 
 other bacilli in neighboring gigantic cells ; I have also seen cases in which the 
 giant cell contains a dark and strongly colored bacillus, and beside it a second, 
 very pale one, which without careful attention would be overlooked. Further- 
 more I have sometimes found spore-bearing bacilli in the interior of giant cells. 
 From all this I conclude that the giant cell is quite a durable formation, that the 
 bacilli, on the contrary, do not possess such duration of life, and that they can 
 only maintain themselves for a considerable time in giant cells, in that a new gen- 
 eration follows a dying one. Sometimes they form spores in the interior of the 
 giant cells, and in this case leave behind them the germs of a later generation. 
 But often enough the vegetation of the bacilli in the cell appears to die out and 
 the empty cell then remains as a monument of their former presence. When 
 one, as is often the case in a tuberculous tissue, finds quite numerous giant cells, 
 and among them only comparatively few supplied with bacilli, one can then take 
 for granted that many of the apparently empty gigantic cells contain spores of 
 tnberculous bacilli; others, on the contrary, mark the places of former vegetations 
 of bacilli, and one is tempted to institute a comparison with a volcanic region in 
 which occur not only single active volcanoes, but a great number slumbering for a 
 time, or completely extinct, these latter nevertheless bearing unmistakable marks 
 of their former activity. 
 
 As to the fate of giant cells when the bacilli in them increases rapidly, we 
 have already spoken. In this case the result is exactly opposed to the one just 
 described ; the giant cell is the conquered party; it is, as it were, burst by the tu- 
 berculous bacilli forcing themselves through the wall of nuclei. Its nuclei 
 perish, dissolve themselves into little grains, and the cell perishes. 
 
 How it is that at one time the bacilli are conquered, or for a long time re- 
 main confined to definite spots and barely hold their own, that at another time 
 their number increases rapidly and all cell elements in their neighborhood quickly 
 
2C JiTIOLOGY OF TUBKECtTLOSIS 
 
 perish, only suppositions can be made, -which cannot here be entered upon, but 
 which I will discuss later. 
 
 The further changes which complete themselves in tuberculous tissue after 
 the formation of the epithelioid and giant cells are all of a regressive nature. 
 For the greater part they belong in the sphere of the processes described by Wei- 
 gert as necrosis of coagulation, and lead to the death or the tuberculously diseased 
 tissue and to the formation of the so-called caseous masses which so frequently 
 form the interior of the tuberculous herds. The tuberculous bacilli usually van- 
 ish very quickly in the caseous masses, so that they are only to be met in young- 
 er herds, and are almost always wanting in older ones. In other cases after the 
 vanishing of the bacilli vegetation, the tuberculous tissue may simply shrink and 
 be changed into firm cellular tissue. 
 
 A very important property of the tuberculous bacilli must be mentioned 
 here. It is the spore-forming property. As is well known, F. Cohn was the first 
 to observe in the so-called hay-bacilli the appearance of shining little bodies which 
 remained when the bacilli perished, had the power of germinating and growing 
 to bacilli, and were to be considered the fruit form of the bacilli, receiving hence 
 from F. Cohn the name of spores. 
 
 The appearance of the spore formation as it shows itself microscopically in 
 bacilli tinged with aniline colors, is to be seen in a very instructive manner on 
 photograph No. 76, Plate 13, in the first volume of these communications. The 
 bacilli appear there with short joints, and mostly consisting of two joints. Some 
 of these joints are evenly dark colored and still resemble completely the spore- 
 free bacilli on photograph 75. 
 
 In many joints one notices, nevertheless, the appearance of a light point which 
 increases in size gradually, while the oJored contents of the joint withdraw 
 more and more to the two ends, and the sides are bordered by fine lines marking 
 the outhnes of the joint. The bright space in the interior of the bacillus joint 
 is the spore which in tliis specimen shows itself not by its brilliancy, since it is 
 imbedded in a strongly light-refracting substance, but only by the absence of 
 coloring material. With few exceptions the bacilli spores do not take the aniline 
 coloring. The division into the articulation does not always appear so sharply 
 defined as in the bacilli of this picture. 
 
 In many sorts of bacilli, as for example in those belonging to inflamma- 
 tion-of-the-spleen, the members appear closely joined together and form a con- 
 tinuous tliread which contains the uncolorcd spores at regular intervals. The 
 spore formation of the tuberculous bacilli conducts itself in like fashion. The 
 bacillus preserves its connection and does not fall apart into separate joints, but 
 a bright body appears in every joint so that the bacillus after coloring resembles 
 a little dark thread interrupted by bright egg-shaped spaces. By the use of the 
 strongest systems and great magnifying power it may then be shown that the 
 spore-bearing tuberculous bacillus presents exactly the same appearance as the 
 spore-bearing bacilli of inflammation-of-the-splcen, only in greatly diminished 
 proportions. The spores are egg-shaped, bounded by a delicaie colored line, and 
 are present usually in the number of two to six in one bacillus. Since every sin- 
 gle spore takes possession of one joint, from their numbers we can decide upon 
 the number of the joints of the bacillus, that is to say of the single elements out 
 
ETIOLOGY OF TUBEECULOBIS. 2Y 
 
 of ■which the same is formed. If a substance containing spore-bearing tubercu- 
 lous bacilli be examined in the uncolored condition and in less strongly refractive 
 liquids, the bacilli appear to be provided with brilliantly shining little bodies; 
 these last can therefore not be vacuoles or simple gaps in the protoplasm of the 
 bacillus, but must be genuine spores. 
 
 After these remarks as to the universal qualities of tuberculous bacilli, I now 
 turn to the description of their action in the various tuberculous processes. 
 
 A. TUBERCULOSIS IN MAN. 
 I. — Miliary Tubekculosis. 
 
 Nineteen cases in all vyere examined in which the tubercles were found in 
 the form of miliary and sub-miliary little grey knots, mostly provided with a 
 whitish or weak yellowish centre, scattered in several organs, lungs, brain, liver, 
 spleen and kidneys. The bacilli were wanting in the tuberculous knots in no 
 one of these cases. The smaller and younger the knots were, so much the more 
 plentiful were the bacilli, and they were thickest at the centre. As 
 soon as the middle of the little knot will no longer take nucleus coloring, as 
 soon, therefore, as the caseous degeneration begins, the number of bacilli de- 
 creases immediately. In the larger knots, whose centres had already experienced 
 a far-reaching caseous change, few bacilli were to be found, and those only to be 
 found between the nuclei of the epithelioid cells occurring in the periphery of the 
 knot. Now and then one finds in the giant cells occurring on the border of the 
 caseous herd, single bacilli or groups of the same. A noticeable fea- 
 ture which re-appears in the chronic processes of the lungs is this, that 
 most giant cells contain black pigment grains beside which the bacilli are 
 still easily to be distinguished. In other organs I have not seen such 
 pigment-bearing giant cells, and their presence appears to be limited to tlie lungs. 
 From the analogy of other results obtained from the lungs of swine and olh( r 
 animals, to be mentioned later, I might suppose that we here have before us 
 giant cells which originally developed in the interior of an alveolus and took into 
 themselves the pigment of the perishing cells present in the alveolus. Tliis view 
 is taken by Watson Cheyne on the ground of direct observations of giant cells 
 which were found in alveoli of the human lung. (See Practitioner, April, 18S3). 
 These cells, which first developed in the alveoli next to the little knots, are after- 
 wards taken up by them as the knots extend. In many of the older knots the 
 bacilli appear to have vanished completely. Nevertheless, we must remember 
 that the prepared sections of the larger tubercles always contain only fragmtntp, 
 and that if the bacilli are wanting their absence from the whole knot is not there- 
 by proved. The relations here are similar to those formerly described in regard 
 to the giant cells, that is to say, that beside those knots which still contain abun- 
 dant bacilli others occur in which the bacilli have eithei entirely vanished or 
 have left spores behind them. Nevertheless, if a sufficient number of sections 
 are examined, one almost always finds spots rich in bacilli, and it would not be 
 right from the results of a few specimens to give a judgment as to the presence 
 or absence of bacilli in miliary tubercles. 
 
 In miliary tuberculosis of the liver and sple( n, I have seen bacilli almost ex- 
 clusively in the giant cells. Especially in the spleen, beside completely developed 
 
28 ETIOLOGY OF TUBKKCULOSIS. 
 
 tubercles, there are often found giant cells of considerable size, which are almost 
 isolated or only surrounded by a few epithelioid cells, and are regularly the seat 
 of one to three tuberculous bacilli. 
 
 The tubercles of the membrane of the brain were, almost -without exception, 
 rich in tuberculous bacilli. Frequently the latter are found in the immediate 
 neighborhood of small arteries beside which are spindle-formed heaps of epithe- 
 lioid cells ; between the latter the bacilli are strewn in quite unifcrm numbers. 
 But in many places the bacilli are present in such thick masses that their 
 presence makes itself known, under a weak magnifying power through the blue 
 color of the parts in question. In this case they are principally round cells, 
 therefore younger cell formations, among which the bacilli vegetation has its seat. 
 Sometimes aho I have seen bacilli in the interior of the vasa. 
 
 Of miliary tubercles of the choroidee ouly one case was at my disposal, and 
 that I owe to Prof. Weigert. Here also were formed herds without nuclei, (that 
 is to say already developed caseous degeneration), which were surrounded by 
 large giant cells, and many epithelioid cells. Partly in the giant cells, but also 
 partly outside of them, between the epithelioid cells, a good many tuberculous 
 bacilli were present. 
 
 With the exception of one case, comparatively old caseous herds were always 
 to be found, especially in the lungs and bronchial glands. Also in these herds, 
 which may be considerd the point of departure for miliary tuberculosis, the pres- 
 ence of bacilli were proved in tue cases which were examined with reference to 
 them. Often, to be sure, they were only found sparsely in the periphery of the 
 herd, but sometimes one discovered nests of dense masses of ba'-illi. 
 
 It would lead too far if I should here describe particularly all the cases of 
 miliary tuberculosis which I have examined, and I select, therefore, only some of 
 the most characteristic. 
 
 1. — Workman, thirty-six years old. Strong man, who had not felt unwell un- 
 til fourteen days before being taken to the hospital, attacked with coughing; 
 pains in the chest and moderate fever. The symptoms observed in the hospital 
 were only slightly characteristic, and corresponded with those of catarrhal pneu- 
 monia. Under increase of dyspnce the patient's powers sank rapidly and he died 
 four days after his reception into the hospital. In the journal of dissection the 
 following is worthy of mention. The pleura on both sides occupied by numer- 
 ous little miliary knots. Both lungs infiltrated, greyish-red, and many lit'le 
 miliary grey knots present ; the larger knots show caseous degeneration. In the 
 conns arteriosus of the heart several sub-miliary grey knots of the endocard. On 
 the closing border of the mitralis eruption of firm knots varying from miliary to 
 the size of a pea. In the liver not very numerous little knots. Both kidneys 
 contain grey little miliary knots in the pithy substance as well as in the outer 
 coating in abundance. The hollow of the right kidney dilated, and in the same 
 two defecti with indented borders and caseous base whose diameter is about IJ 
 to 3 cm. A caseous deposit of the size of a hazel nut in one papilla. Bladder 
 free from tubercles. In the prostata some caseous deposits. In the urethra 
 abundant little miliary knots. Caseous degeneration of the accessory testicles, 
 partly with caseous softening, drawn in scars on the scrotum. In the testicles 
 themselves abundant deposits of little grey miliary knots. The thoracic duct 
 
iETIOLOGY OF TUBERCTIL0SI8. 
 
 29 
 
 dilated, on several spots on its wall caseous thickening, and on the inner surface 
 of the same some defecli provided -with caseous base. 
 
 Here we Lad a case of chronic tuberculosis of the uro-genital organs. The 
 tuberculosis of the thoracic duct connected itself with this and had as a conse- 
 quence, the breaking out of the general miliary tuberculosis. This case according 
 to its origin belongs to the form of miliary tuberculosis described by Ponfick and 
 forms a typical example of the same. The microscopic returns corresponded ex- 
 actly with the description of the action of the bacilli as previously sketched. 
 The tubercles in the lung tissue showed themselves comparatively small, and for 
 the most part contained bacilli in abundance. Some contained so many that 
 under a weak magnifying power a bluish color showed itself in the middle. 
 
 Many gigantic cells were also found in the tubercles of the liver and spleen, 
 which for the most part were supplied with bacilli. Very numerous bacilli were 
 present on the edge and in the surroundings of the herd in the papilla of the kid- 
 neys. At single points in the surroundings of this herd, the bacilli had collected 
 in groups in the urethra, and the peculiar grouping here manifest suggested the 
 figures which they take in blood serum culturen, and which ai'e to be mentioned 
 later. Whether the bacilli in this case reached the urethra via the course of the 
 blood or whether they spread from the neighboring tissue, could not be decided. 
 In another tuberculous kidney which I received from Prof. Weigert, numerous 
 glomeruli and the neighboring urethra were covered with masses of bacilli, which 
 leads us to conclude that the bacilli can make their way from the course of the 
 blood into the urethra and from there perhaps into the urine. 
 
 2. — A second case of tuberculosis of the thoracic duct in a man forty-eight 
 years old shows an analogous behavior. The tuberculous process had been here 
 spread from the caseous mediastinal glands to the thoracic duct, and has brought 
 about miliary tuberculosis of the lungs, liver, spleen and kidneys. Death fol- 
 lowed later than in the first case ; the tuberculous eruption was not so abundant, 
 the single knots reached a greater size, were more caseous and contained a cor- 
 respondingly smaller number of bacilli. 
 
 S.^Nine year old boy. Said to have been takensick only a few days before 
 his admission into the hospital. At his entrance into the hospital diseased senso- 
 rium, great restlessness and delirium with high fever. In the following days 
 bronchial phenoifiena showed themselves, death ten days later. Dissection 
 showed : caseous swellmg of the bronchial glands ; broncho-pneumonia herds in 
 both lower lobes of the lung. Besides these, numerous grey miliary and sub- 
 miliary tubercles in the lungs, in the enlarged spleen, in the liver and in the kid- 
 neys. At the base of the brain, and in the surrounding of the vessels a slight 
 muddincss (triibung) and a great number of little grey knots. 
 
 In the tubercles of the lungs, liver and kidneys aud spleen, bacilli were found 
 in varying abtmdance. The tubercles of the pia mater were very abundantly 
 supplied with them. 
 
 In the caseous bronchial glands belonging to this case, large quantities of 
 bacilli were found, and not only on the borders of the caseous herd, but forcing 
 themselves far into it. The parts of the gland tissue which were not yet necro- 
 tized contained numerous gigantic cells which were noticeable for the multitude 
 of enclosed tuberculous bacilli, and for the radiate arrangement of the same. 
 
30 ETIOLOGY OF TUBEECtiLOSIS. 
 
 Plainly the tuberculous process in tlie Lroncliial glands had only lately began 
 and had spread rapidly. The gland tissue had become very quickly necrotized 
 and softened under t„e influence of the tuberculous bacilli. Somewhere there 
 must have been a breaking through into a vasalumen (gefiisslumen) and so con- 
 siderable numbers of bacilli have got into the course of the blood to have caused 
 the general eruption of miliary tubercles. The location of this breach was, 
 however, not to be found in this case. That the same is not always easy to find 
 may be seen from the following case. 
 
 4. — A strong man of about thirty years died after a sickness which showed 
 typhoid symptoms and had not lasted longer than three weeks. From the dissec- 
 tion it appeared that there were very many grey little miliary knots in the lungs, 
 liver and kidneys, as well as in the greatly enlarged spleen. The bronchial 
 glands were swollen, of a marrow-like nature, but not caseous. Also, moreover, 
 no older caseous herd could be proved, in spite of the most thorough investiga- 
 tion, so that one was loth to make a diagnosis of miliary tuberculosis. The in- 
 testines and mesenterial glands were not changed. 
 
 Microscopic investigation gave the following very noteworthy result : Sec- 
 tions from the bronchial glands showed wide-spread spots bare of nuclei, and 
 which were only filled with black pigment grains, and numerous fragments of 
 perished nuclei, together with dense swarms of tuberculous bacilli. These last 
 were heaped together in such masses in the immediate neighborhood of little 
 arteries that the vasalumen (gefasslumen) appeared to be surrounded by a blue 
 court, even under a slight magnifying power. A greater magnifying 
 power showed these blue masses to be composed of bacilli. In single 
 places the bacilli forced themselves even into the interior of the vasa, and there 
 could be no doubt, therefore, that they found their way into the blood in this 
 manner, and were transported in all directions in great quantity. A third method 
 was thereby sought by which a general tuberculous infection and the miliary tu- 
 berculosis conditioned upon it could take place, after Ponflck had succeeded in 
 discovering one of these ways in the thoracic duct, and after Weigert had taught 
 the second, and to all appearance by far the most frequent, in the breaking 
 through of tuberculous masses into the veins. 
 
 The miliary tubercles of the spleen and lungs contained a good many bacilli, 
 partly also in the giant cells. 
 
 But this case was of great interest in another way. It appeared, namely, 
 that numerous capillaries were filled for short distances with micrococci. Under 
 the double coloring treatment, the tuberculous bacilli took, as they always do, 
 the blue coloring, the micrococci, on the contrary, the brown color. In many 
 places in the same field of vision, and at slight distances from each other, brown 
 colored micrococci and blue colored bacilli were to be seen. The capillary mi 
 crococci embolism were moreover very numerous in the lungs, and especially in 
 the spleen. They had not as yet led to striking changes in their surroundings, 
 such as heaping together of nuclei or necrosis, and must therefore have appeared 
 not many days before death. The combination of a bacilli and a micrococci in- 
 vasion as it occurred here, belongs to the mixed infections whose appearance 
 seems not to be rare. Such mixed infections can be generated artificially in ani- 
 mals by simultaneous or closely following inoculation with various infeclioua 
 
.arrioLOGY of tobeectjlosis. 31 
 
 materials, for example, by using inflainmation-of-the-spleen and scepticsemic 
 bacilli in the case of mice. Also tuberculosis and inflammation-of-lhe-fpleen can 
 exist simultaneously in the same animal. I have inoculated a number of guinea 
 pigs -which were tuberculous to a great degree with inflammation-of-the-spleen 
 bacilli. In consequence of this, the animals were attacked with inflammation cf 
 the spleen and died. Several of them had very large numbers of tuberculous 
 bacilli in the lungs and spleen, and in sections from these, by double colorinf, 
 the tuberculous bacilli took the blue,. and the very numerous inflammation-of-thu 
 spleen bacilli took the brown color. As a further instance of a spontaneous!}' 
 arising mixed infection, the occurrence at micrococci herds in typhus is to be nr- 
 ticfd. Further, Brieger and Ehrlich* have drawn attention to a combination of 
 typhus with malignant cedema, in which case the very fitting expression mixed 
 infection was first used. It is therefore plain that we have such a mixed infection 
 in the case here spoken of. The tuberculous disease of the bronchial glands 
 formed the primary infection, which, in consequence of the rapid growth of the 
 bacilli and their forcing themselves into the arteries, led to general miliary tuber- 
 culosis. Not until this disease was well established, the strength of the organism 
 had been very much lowered, and therewith probably the ground for the micro- 
 cocci invasion had been prepared, did the latter follow ; proceeding to all appear- 
 ance from an ulcerated defekt (imperfection) on the tongue, and causing in 
 connection with the miliary tuberculosis, death so much the more quickly. 
 
 A similar combination of tuberculous bacilli in the miliary tubercles of the 
 lungs, and micrococci in the neighboring vessels, has been observed by Watson 
 Cheyne, t and it may therefore probably be accepted that with a little attention 
 this sort of mixed infection might be not infrequently found. 
 
 Of the other case of miliary tuberculosis coming under examination, the fol- 
 owing may be briefly sketched : 
 
 5. — Boy of eight years. Caseous bronchial tubes, numerous miliary tuber- 
 cles in the lungs, spleen, liver and kidneys. The little knots of the lungs were 
 thoroughly provided with large nuoleusless caseous centres, and on the circum- 
 ferential parts of the same, single little groups of bacilli were to be found. Tu- 
 berculous bacilli could also be proved in some giant cells on the border of the 
 caseous centers. Bacilli-bearing giant cells were also to be found In the spleen. 
 In this case I did not succeed in finding bacilli in the little knots of the liver and 
 kidneys. On the contrary they were abundantly present in little nests in the 
 bronchial glands. 
 
 6. — A strongly built and vigorous man, thirty-four years old, had suffered 
 from a cough for about three weeks before his entrance into the hospital. Quite 
 high fever and broncho-pneumonia symptoms, cerebral phenomena soon ap- 
 peared, and by means of the opthalmoscope, tuberculosis of the choroidea could 
 be clearly shown. Death followed fourteen days after entrance to the hospital. 
 Caseous confluent herds in the tips of both lungs, quite large, not very thickly 
 sown miliary tubercles in the lungs, spleen and liver, bronchial glands caseous 
 In the little knots of the lungs tuberculous bacilli found singly in the periphery. 
 
 • Berl. kiln. Wochensohrift 1882. No. 44. 
 
 tTlie Practitioner, Vol. XXX. No. 4, Apr., 1883, p. 295. 
 
g2 JETIOLOGY OF TTjBEECULOSlS. 
 
 Liver and spleen contained giant cells, among them some with bacilli. In the 
 broncliial glands also, small groups of bacilli could be shown only in a few ^pols. 
 
 7.— Baker's apprentice, seventeen years old, anaemic, of a delicate build, had 
 coughed for half a year, was taken into the hospital with a pleuritic exudation 
 from the right side. Puncturing the thorax brought out 500 ccm. of clear serous 
 liquid. Four weeks later cerebral symptoms appeared, and after another two 
 weeks death followed. Dissection showed tuberculous pleurisy, miliary tubercu- 
 losis of the lungs and tuberculous meningitis.. In the little knots of the lungs, as 
 also in those of the Dia mater, tuberculous bacilli were found and in some places 
 very abundantly. 
 
 8,— Six-year-old girl. Bronchial glands and partly verkalkt (ossified.) Sin- 
 gle lobuliirc (lobular, lobe-shaped ? ) red, hepatized herds in the lungs, within 
 which the bronchia3 were supplied with purulent contents. At the base of the 
 brain muddy "sulzig" infiltrations of the pia. Numerous miliary and sub-mil- 
 iary knots in the vessels of the fossa Sylvii. Microscopic examination shewed 
 tuberculous bacilli im small numbers in scattered spots in the bronchial glands. In 
 the hepatized parts of the lung the alveoli were found filled with bacteria of va- 
 rious sorts, (aspirations pneumonia). The meningeal tubercles were very abun- 
 dantly supplied with tuberculous bacilli. 
 
 9. — Workman thirty-four years of age, drunkard, treated two years before on 
 account of scrofula of the wrist bones. Complication with "lymphangitischen" 
 (pertaining to inflammation of the lymph vessels) abscesses on the upper part of 
 the left foot and upper part of the thigh. Death, with cerebral symptoms, after 
 seven weeks' stay in the hospital. The dissection showed caseous infiltration 
 with formation of cavities in the tips of both lungs, miliary tubercles in both 
 lungs and at the base of the brain. Quite numerous tuberculous bacilli were 
 found in the tubercles of the lungs as well as in the meningeal tubercles. 
 
 10. — Five year old boy. Wide-spread caseous degeneration of the bronchial 
 glands. In the tip of the left lung a caseous herd larger than a hazel nut, with 
 the centre in a state of disorganization. A moderate number of comparatively 
 large miliary tubercles in the lungs. Quite numerous grey and yellowish little 
 caseous knots in liver, spleen and kidneys. The pia mater of the basis of the 
 brain greyish, yellow "sulzig" infiltrated. Under microscopic investigation nu- 
 merous tuberculous bacilli were found, partly enclosed by giant cells, in the 
 bronchial glands ; also great heaps of bacilli in the tubercles of the brain mem- 
 branes. In the little knots of the lungs, liver, spleen and kidneys only compara- 
 tively few bacilli were present. 
 
 11. — A one-year-old child very much afflicted with atrophy, said to have 
 been taken sick with a cough eight days before its arrival at the hospital. The 
 bronchial symptoms and dyspncea which showed themselves in the first examina- 
 tion, increased, and the child died two and one-half weeks later. The right upper 
 lobe of the lung was found to be caseously infiltrated, bronchial glands caseous. 
 Numerous miliary tubercles on the peritoneum, on the diaphragm and in the spleen. 
 Tuberculous meningitis. In the meningeal tubercles numerous tuberculous 
 bacilli. Nests of bacilli in the caseous parts of the lungs and in the bronchial 
 glands. Scattered bacilli in the tubercles of the peritoneum and diaphragu', ex- 
 clusively enclosed in giant cells. A moderate number of bacilli in the tubercles 
 of the spleen. 
 
Etiology of TifBteEocLosis. So 
 
 2. — Phthisis of the Lungs. 
 
 Twenty-nine cases were examined and tlie tuberculous bacilli were wanting 
 in none of them. The number of bacilli, to be sure, varied greatly, but one could 
 recognize here as in miliary tuberculosis, in so far a connection between the number 
 of the bacilli and the phthisic process, that the bacilli were found most abundantly 
 in fresh caseous infiltrations and in the interior of cavities whose environment 
 was in a state of rapid decay. The bacilli were found less abundantly in the 
 cavities provided with compact, callous walls; they were most scarce in scarred, 
 shrivelled lung tissues containing much pigment. The more their number decreases 
 the more they confine themselves to the interior of the giant cells. One may not 
 conclude, however, that each single case conducts itself throughout in a like 
 manner in regard to bacilli, that one phthisic lungshows throughout a great number 
 of bacilli, another, on the contrary, only scattered ones. To be sure it may some- 
 times be so, but it will usually be found that in the same lung some parts are en- 
 tirely free from bacilli, but that in single spots dense nests of the same are present. 
 So especially may cavities of some extent appear almost or wholly free from 
 bacilli, until, by continued investigation, one suddenly finds one or more nests of 
 tubercul(ju3 bacilli in a hidden side indentation or encamped close beside the wall 
 of the cavity, but not yet melted into it, and finds them, too, so thickly crowded 
 together that even under a low magnifying power they appear as dark blue spots. 
 For the examination of phthisic lungs it follows that one may not content himself 
 vyith looking through a number of sections from any one spot, for example from 
 a piece of the wall of a cavity, but should examine as great a variety of places as 
 possible, and should take not too small a number of specimens from each. Only 
 80 can one get a correct conception of the behavior of tuberculous bacilli in the 
 case in question. 
 
 After the experience gained in my investigations I should represent the 
 relations of the bacilli to phthisic processes in the following manner : In the 
 beginning only a few, or single bacilli get into the lung, and on account of 
 their slow growth are very soon enclosed by a cell infiltration and thereby 
 hindered from forcing themselves more quickly into the surroundings of the 
 infectious spot. The bacilli, nevertheless, do not perish in the cell infiltration, 
 but cause necrosis and caseous degeneration in the centre of the cell mass, just 
 as in miliary tuberculosis. The first beginning of phthisis would, if one could 
 succeed in getting a sight of it, completely resemble a miliary tuberculosis. 
 The little knot gradually takes larger dimensions and becomes constantly 
 more unlike the miliary tubercle. An analogy of this stage might be found, 
 however, in the not rarely occurring cases of large solitary tubercles, which 
 do not always appear solitary but also scattered to a certain extent in various 
 organs. These also I would consider as having proceeded from single miliary 
 tubercles whose number is so small that they do not bring about the immediate 
 death of their bearer, as is the case in general miliary tuberculosis, but which 
 rather gain time for farther growth, and can finally grow to caseous herds of 
 a good size. It is quite certain that the phthisic process takes the same devel- 
 opment, that, namely, proceeding from alittle miliary knot there grows a con- 
 stantly spreading caseous herd. In the lungs the relations shape themselves 
 very peculiarly, because the increasing caseous herd does not remain closed, 
 
34 J;tlOLO&Y OF TUBKEOtTLOSlS. 
 
 but after a shorter or longer time makes its way into the bronchise, empties 
 itself and so is changed into a cavity. The further increase of the cavity goes 
 on in a very irregular manner according as the process of vegetation in the 
 tuberculous bacilli makes a halt in single places for a shorter or longer time, 
 or continues, and according to this indentations or shrivelling are formed in 
 places. Taken in general, the cavity, howrever large or irregular formed, re- 
 tains the essential properties of the tuberculous caseous herd ; necrotic masses 
 in the interior, joined to these tovfards the outside nests of epithelioid cells 
 with gigantic cells sandwiched in, and in the giant cells often tuberculous 
 bacilli. An exception occurs only in so far as the tuberculous bacilli in the 
 cavity appear in comparative abundance also in the interior of necrotic masses, 
 which in the caseous herds remaining permanently closed is not usually the 
 case. Probably this has its foundation in the fact that the masses dead, and 
 to a certa,in extent used up as a breeding-^ound for bacilli, are constantly 
 being emptied, and the parting of the walls of the cavity give constantly a new 
 food material for bacilli. 
 
 In this manner the usual chronic form of phthisis would run its course. 
 In this usual course the vegetation of the bacilli is a very slow one and the 
 occurrence of the bacilli very sparse, and essentially confined to the giant cells 
 in the immediate surrounding of the cavities and to the contents of the same. 
 The circumstance is very noteworthy that even in comparatively small tuber- 
 culous herds the growth and dispersion of the bacilli is not uniform but dis- 
 continous. In large herds, and especially in larger cavities, this behavior, 
 which has already been touched upon, is always more striking. Widespread 
 spaces of the cavity may be wholly free from bacilli and sometimes the bacilli 
 may be confined to single spots of very slight extent. From this we may con- 
 clude that the conditions of life for bacilli in a tuberculous herd are not every- 
 where equally favorable, and probably also in regard to time may be subject 
 to fluctuations. The bacilli must then vanish from the places which no longer 
 give them suitable breeding-ground. In this ease at one time only a temporary 
 freedom from the parasites can take place, when the bacilli from the neighbor- 
 hood later force themselves in or if spores have been left behind which may 
 develop under more favorable conditions. At another time a lasting freedom 
 of the diseased spot from bacilli can take place when the just mentioned con- 
 ditions for the reviving of the bacilli vegetation do not occur. Shrivelling, 
 scarring and healing will follow then in such a place. One can think that 
 since these things may take place partially in the periphery of the tuberculous 
 herd, the same might happen in the whole compass of the herd, and so a com- 
 plete healing take place. Analogous relations are found in other diseases condi- 
 tioned upon bacteria which also spread themselves out centrifugally from the 
 original spot of infection, but can show in their progress considerable irregulari- 
 ties sometimes cease to grow at one point, sometimes thrive and spread rapidly, 
 as is the case, for example, in erysipelas. 
 
 The development of a single tuberculous herd running its course in the 
 lung under the type of chronic phthisis can be complicated in many ways, if 
 the tuberculous bacilli in any manner get out of the reach of the original 
 herd into other places and there give rise to the development of secondary 
 
^teriOLOGY OF TOBERCULOSiS. 35 
 
 herds. This proceeding can complete itself in various ways. The bacilli can 
 get into the larger blood vessels of the lungs, be strewn over the whole body 
 in greater or lesser numbers by the course of the blood and cause miliary tub- 
 erculosis. Then, according to all appearance, the bacilli have the power of 
 spreading themselves also byway of the course of the lymph, of forcibg them- 
 selvesinto thebronchialglands and causing secondary tuberculous changes. The 
 bacilli conveyed from the cavities into tlie air passages find by far the most fre- 
 quent opportunities of fixing themselves in other places. Oftentimes tluy nestle 
 themselves in otlier parts of the air passages and more especially into thelarynx. 
 Often if the sputum be swallowed they plant themselves in the intestinal 
 passage. 
 
 The usual course of the phthisis must then be most affected when the ba- 
 cilli-bearing pus from the cavities is on the way to be conveyed outward by 
 the bronchise, but by some unfortunate disturbance of the motions of respira- 
 tion is again aspirated and brought into parts of the lung until then healthy. 
 When only a slight quantity, poor in bacilli, is aspirated, it can only bring 
 about the beginning of a comparatively small number of infectious herds. 
 These will gradually grow and develop into cavities according to the place 
 that the bacilli-bearing masses reach, sometimes in the immediate neighbor- 
 hood of the mother herd, sometimes some distance from it, even in the other 
 previously healthy lung, and will from small beginnings grow just as slowly 
 as the first tuberculous herd. But as soon as considerable quantities of the 
 bacilli-rich contents of the cavities are breathed in, and wide-spread parts of 
 the lung are overflowed, as it were, with infectious material, as appears not 
 seldom to be the case, then the formation of single tuberculous knots is not 
 the first step, but tuberculous infiltrations arise which show us by the lobed 
 and even lobuled (lobuliire) arrangement that they cane from the respiratory 
 passages. The penetration of the tuberculous bacilli en masse has not as a 
 consequence heaps of closed cells and the formation of giant cells, as is the case 
 when individual bacilli appear, but necrosis of the component parts of the cells 
 in the at' acked tissue spreads widely and with comparative quickness. In 
 consequence wide-spread caseous degenerations form in many places, also 
 rapid dissolution of the tissue, with development of cavities which bear another 
 character than those formerly described. 
 
 While these cavities possess compact, firm walls in which are found giant 
 cells and scattered tuberculous bacilli, the walls of cavities formed in the de- 
 composing and widely caseous lung tissue are permeated by a thick bacilli 
 vegetation. They do not consist of condensed callous tissue, which only 
 melts away slowly under the influence of the bacilli, but the wall allows us 
 still plainly to recognize the structure of the alveoli which are filled with the 
 caseous substance rich in bacilli, but are in the act of losing their coherence, 
 and falling to pieces. These conditions are usually described as caseous pneu- 
 monia, acute phthisis, etc. 
 
 The most various combinations of these two just described processes, that 
 of a tuberculous herd proceeding from a single infectious herd and spreading 
 slowly, and the caseous infiltrations arising from a flood of infectious material, 
 unile to give a most varied conception of the tuberculous destruction of the 
 lungs covered hf the general name phthisis. 
 
36 ETIOLOGY OF TUBBECUL08IS. 
 
 It deserves still to be mentiotied that the aspirated masses giving n»e to 
 caseous infiltration do not necessarily always spring from a tuberculous herd 
 of the lung. Several recorded observations of animals are at my disposal 
 which prove that a caseous ulceration of the tonsils, or a tuberculous ulcer on 
 the superior margin of the lower jaw, which had developed itself in a rabbit in 
 consequence of a bite, also in one case a caseous bronchial gland communica- 
 ting with the air passages, can furnish the bacili-bearing masses which are 
 breathed into the lungs. On this account therefore, also in man, tuberculous 
 processes in the larynx, throat and mouth, as well as caseous bronchial glands, 
 so soon as the latter empty their contents into the bronchise, are to be kept in 
 sight as points of departure for caieous infiltrations of the lungs. 
 
 The conduct of the secretion of tuberculous lungs, the phthisic sputum, 
 deserves special consideration. Since tuberculous bacilli occur in no other 
 diseased conditions than in the tuberculous, the demonstration of their presence 
 has great diagnostic importance. The first examinations which I made of 
 phthisic sputum led to the result that abundant numbers of bacilli showed 
 themselves in the sputum in half the cases examined ; in other cases only a 
 few bacilli were to be found, and in many they seemed to be wanting. But 
 when I used Ehrlich's color treatment, and had had more practice among the 
 by no means few cases examined, not one case more occurred in which the 
 bacilli were wanting. I do not mean to say by this, that in single cases, after 
 repeated investigation one may not fail to find bacilli, but in general it must 
 be considered a settled fact, on account of the numerous results in the mean 
 time published also by other investigators, that the bacilli, with few exceptions, 
 constantly occur in phthisic sputum, are wanting in the sputum of other lung 
 diseases, and thereby give an unmistakable diagnostic characteristic mark of 
 the presence of tuberculous affections of the lungs. 
 
 The bacilli often occur in the sputum in quite considerable numbers. Ap- 
 parently these are always cases in which there is rapid dissolving of the case- 
 ously infiltrated parts of the lungs, and in which the cavity walls have mixed 
 their secretion with the sputum. The well known caseous fragments which 
 from the beginning have been considered as a specially characteristic com- 
 ponent part of phthisic sputum, consist almost wholly of masses of bacilli. One 
 can think that these caseous fragments have arisen from compact bacilli masses, 
 such as are sometimes found on the inner wall of the cavities, becoming 
 loosened, and swept away by the secretion of the cavity. Xeverthelcss, one 
 often meets cases in which the sputum is very poor in bacilli, and must look 
 through a number of specimens, indeed sometimes must repeat the investiga- 
 tions for several successive days before he succeeds in discovering bacilli. Tte 
 sputum mvestigations carried on for a long time by Gaffky with a number of 
 phthisic patients, which are published in this volume of the " Mittheilungen " 
 give the best idea of the frequency of bacilli in phthisic sputum. 
 
 Very often the bacilli occurring in the sputum are spore-bearing, and this 
 appears to be especially the aase when the bacilli could develop themselves 
 unhindered and abundantly, as is the case in caseous infiltrations. Just those 
 relations are of the greatest importance for the aetiology of tuberculosis, and 
 we shall come back to them later. 
 
^TIOIiOGT OF T0BEKCtJLO8I8. 37 
 
 Since the sputum is always more or less mixed ■with saliva, it contains 
 regularly, beside the tuberculous bacilli, other sorts of bacteria, the abundance 
 and variety of these depending upon the amount of saliva and mucus from the 
 cavity of the mouth mixed with it. 
 
 If sputum is kept for some time in a vessel the tuberculous bacilli remain 
 unchanged, both in reference to their number and to their responsiveness to 
 coloring matter. The other bacteria, on the contrary, increase rapidly in 
 numbers, other bacteria coming from the air or accidental defilement, appear, 
 and a real decay develops itself very soon. Under microscopic investigation 
 one finds, then, numberless bacteria occurring in the fresh sputum out of the 
 cavity of the mouth, or those appearing in decaying sputum, which act in re- 
 gard to color like the tuberculous bacilli. The latter always keep their intense 
 blue color if the coloring is carried on according to the rule, while all other 
 bacteria appear dyed brown. 
 
 It is still to be mentioned that sometimes bacteria force themselves also 
 into the cavities, and can increase in their secretions so that, in thise cases, 
 one finds in the contents of the cavity not only tuberculous bacilli, but other 
 bacteria. I concerned myself, nevertheless, in the few cases over which my ob- 
 servations of this sort extended, only with certain sorts of bacteria, so one need 
 not suppose that a sort of decay in the contents of the cavity, as in the sputum 
 exposed to the air, existed, but it must be assumed that of the various sorts 
 of bacteria which accident had brought into the cavities, only certain definite 
 kinds can thrive there. These then either lead a harmless parasitic life in the 
 contents of the cavity, as for example, the bacteria of the green pus, which I 
 have repeatedly found in large old cavities, or they, as it seems, take part in 
 the destructive work of the tuberculous bacilli, as seems to me to be the case 
 with a special sort of micrococci. The latter distinguish themselves by a pe- 
 culiar arrangement, almost regularly forming groups of four, and have on that 
 account at first sight a certain resemblance to sarcine, nevertheless in other 
 ways distinguishing themselves essentially from these. Gafflke has studied the 
 properties of these further* and found that they are disease-producing for 
 many species of animals. Also, in the case in which they were first discovered, 
 they appear to have aided in the quick destruction of the lung tissue. It is 
 much to be wished that in future attention should be paid to these combina- 
 tions of phthisis, because they must lead to the finding of such sorts of bacteria 
 as of themselves possess no or only conditional disease-producing properties 
 for the human organism, but under conditions specially favorable to them, as 
 for example in an ulcerous herd of the lung, can form little nests and have a 
 decisive influence on the further course of the process. Of how much impor. 
 tance such secondarily-working bacteria may be has already been mentioned 
 in the description of miliary tuberculosis and the mixed infection occurring 
 there. 
 
 In connection with phthisis of the lungs, some remarks may here find place 
 in regard to the phthisis of the intestines. Among the twenty-nine cases which 
 I had the opportunity to examine, I received in addition to parts of the phthisic 
 
 •Langenlaeck's Aroiiv., ToL 88, Book 3. 
 
38 ETIOLOGY OF TUBEKCUL08I8 
 
 hmg also, in eight cases pieces of the intestinum tenue with tuberculous ulcer. 
 ations, and just as often caseous mesentric glands. Several times the abscesses 
 of the intestinum tenue were surrounded by fresh tuberculous erruptions, which 
 followed the lymph-passages. 
 
 The growtli of the bacilli appears, at least so far as we can come to a con- 
 clusion from the material at my disposal, to find more favorable conditions in 
 the intestines than is usually the cass in the lungs. It should not therefore 
 surprise us if, in the excrement of a parson suffering from phthisic and tuber- 
 culous abscesses, tuberculous bacilli occur in comparatively large numbers, as 
 Lichtheim first discovered. Among the numberless and very largely staff- 
 formed bacteria of the intestinal contents the microscopic proof of tuberculous 
 bacilli would have proved itself as good as impossible, if it had not been for 
 the spccitic tinc'.orial properties of the latter, which just in this case proved 
 themselves especially useful. Since from several sides the certainty of the 
 proof of tuberculous bacilli in intestinal excrement has been doubted, I urged 
 Dr. Gaffky to undertake a number of investigations. These showed that neither 
 in the excrement of healthy persons nor in those of sick ones, who were not 
 suffering from tuberculous diseases, any sort of bacteria were found which 
 gave the same sort of color-reaction as the tuberculous bacilli. Also in the case 
 of all persons afflicted with phthisis, who were examined in regard to it and 
 who had tuberculous bacilli in the sputum, it was impossible to prove such in 
 the excrement, but they could regularly be shown in such patients when they 
 had plain symptoms of ulcerous disease of the intestines. One observation 
 made by Gaffky during these investigations deserves special mention. Namely, 
 in the contents of the intestines there not seldom occur large spore-bearing 
 bacilli, whose bodies, like those of all other bacteria, take the brown color, while 
 the spores remain colored more or less intensely blue. The spores appear to 
 be more darkly blue the younger they are. When the body of the bacillus 
 perishes and the spore alone remains, siace in size it resembles a large micro- 
 coccus, it can easily be mistaken for one at first sight ; especially when several 
 spores lie near together they cai be very similar to a little heap of large micro- 
 cocci. Probabl}', therefore, the formations described by Lichtheim as blue- 
 colored micrococci are identical with these spores. But it appsars that other 
 bacilli occurring in the intestines form spores, which by Ehrlich's color-treat- 
 ment keep the blue color, for Gaffky found in the excrement of a tuberculous 
 monkey, beside tuberculous bacilli, bacilli of still larger dimensions than those 
 just mentioned. These had not egg-shaped, but very long-extended, almost 
 staff-shaped, spores. The spores were fixed in the ends, and in bacilli of more 
 than one member so arranged that in two neighboring members the spore- 
 bearing ends were turned towards each other and followed in the manner indi- 
 cated here : — - - — . — '- - — ■ The points are spores, the lines bacilli-members, 
 a peculiar arrangement of the spores to which I on another occasion have 
 already drawn attention.* The spores of the anthrax-bacilli, hay and potato 
 bacilli were also tried by Ehrlich's color-method and did not show the reaction, 
 but it is nevertheless veiy probable that still other sorts of bacilli-spores act 
 
 "F. Colm'3 Beitrage zur Biology der Pflanzen. VoL 3, Book 3. 
 
ETIOLOGY OF TUBBECULOSIS. 39 
 
 tinctorially as the sorts described, and that -vrith the help of aniline reaction one 
 would be ab^e to distinguish these sorts of bacilli easily from others. The 
 animal in which the bacilli with staff-shaped spores were found, died and had, 
 as the dissection showed, beside numerous tubercles in the lungs, spleen, etc., 
 several tuberculous abscesses in the intestinum tenue abundantly supplied 
 with tuberculous bacilli. 
 
 From the cases of phthisis examined I will speak of a few which served 
 as points of departure for inoculation and for the culture of tuberculous 
 bacilli . 
 
 1. — A woman of thirty years, whose mother also died of phthisis, suffered 
 for half a year from cough with expectoration. Greatloss of flesh. Occasion- 
 ally slight fever. Death after three months' stay in the hospital. Dissection 
 showed left lung partially deformed as well the upper as the under lobe contain- 
 ing a number of communicating vomicae. Right lung also deformed, containing 
 a large baylike vomica in the upper lobe and several smaller ones in the 
 middle lobe. Spleen, liver, kidneys free from tuberculous changes. Under 
 microscopic investigation only a moderate number of bacilli were found in the 
 contents of the vomicae. In the surroundings of the vomicse, which had com- 
 pact walls, were giant cells grouped around little nucleousless herds and 
 largely supplied with tuberculous bacilli. 
 
 2. — Man twenty-three years of age. His mother said to have suffered from 
 phthisis. Had been in the hospital the year before on account of pleurisy. In the 
 last few months repeated haimoptisis. Besides this diarrhoea. At his reception 
 into the hospital thin, anaemic. Suffocation and bronchial breathing over the 
 point of the right lung. Cough with purulent expectoration. Death after four 
 months. In the right lung large vomicae with partly callous, partly caseously 
 infiltrated walls. On the vocal chords tuberculous ulcerations. Beginning 
 amyloid degeneration of the spleen. Numerous ab£ces3es in the intestines, 
 swelling and caseous degeneration of the mcsentric glands. Also in this case 
 the tuberculous bacilli were present in comparatively small numbers in the 
 contents of the vomicse and in the lung tissue, but, on the contrary, were very 
 numerous at the base of the intestinal abscesses and in the caseous mesentric 
 glands. 
 
 3. — Workman of forty-three years, quite strongly built. No heredity could 
 be proved. Had suffered for three months from cough, expectoration and in- 
 creasing weakness. Of late his troubles, especially dyspnoea, had grown much 
 worse. Death after twelve days' stay in the hospital. In the tips of both lungs 
 vomicse of moderate size, wide-spread caseous infiltration with occasional 
 softening and formation of vomicfe in the middle and lower parts of the lung. 
 Ulceration in the larynx. In the vomicse as well as in the caseously infiltrated 
 lung tissue, bacilli were found in great quantities. 
 
 4.— Man of thirty-two years, not hereditarily burdened. Said to have been 
 sick only four weeks. At his reception into the hospital anaemic, emaciated. 
 Death after six weeks' stay in the hospital. In both lungs numerous vomicae 
 of varying size whose surroundings for a considerable distance were caseously 
 infiltrated. Some smaller vomicte lay near the surface and showed as slight 
 protuberances. These were used to obtain rein culturen. 
 
40 ETIOLOGY OF TUBBEOULOSI8. 
 
 5. —Servant girl of nineteen years ; mother died of phthisis ; had suffered 
 for a year from coiigh ; of a delicate build, short hreathed and had profuse 
 sweats. Death after seven weeks' stay in the hospital. In the left upper lobe 
 of the lung a moderately large vomica. The remaining part of the lobe infll. 
 trated and lobular, (lobulilre ?) caseous herds, close together, partly with central 
 decay. On the right almost the whole lung infiltrated with greyish yellow 
 caseous masses and with many softened spots. In the trachea flat ulcerations. 
 In the ileum and in the beginning of the colon numerous abscesses with indented 
 borders. Mesenti ic glands partly freshly cascously infiltrated. As well in the 
 interior of the vomicas as in the caseously infiltrated parts of both lungs extra- 
 ordinary numbers of bacilli were found, mostly heaped together in nests. Also 
 in the intestinal abscesses and mesentric gland tuberculous bacilli were present 
 in considerable numbers. 
 
 3. — Tdbeeoulosis of Vaeious Oegans. 
 
 The cases of tuberculosis examined by me to be mentioned under this di- 
 vision concern single organs which have been obtained, partly from operations, 
 partly from sections, without my knowing anything further of the course of 
 the disease or of the other results obtained from the sections. I can on this 
 account only mention them summarily here. 
 
 Two cases of tuberculous abscess of the tongue. At the base of the ab- 
 scesses and in places forcing themselves deep into the tissue of the tongue, 
 thick swarms of tuberculous bacilli were found. 
 
 Tuberculous bacilli were just as abundantly present in four cases of tuber- 
 culosis of the pelvis of the kidneys, in one case of tuberculosis of the bladder 
 and of the urethra, once in tuberculosis of the surenal gland, and in a case of 
 tuberculosis of the uterus and of the tubi. 
 
 On the contrary, the number of tuberculous bacilli was very small in five 
 tuberculous testicles removed by operations. They could only be proved here 
 singly in the numerously present giant cells. 
 
 Just the same behavior showed itself also in two cases of large solitary tu- 
 berculous herds of the brain. The appearance of the bacilli here also confined 
 itself to the giant cells. 
 
 The only case belonging here in which no tuberculous bacilli at all could 
 be proved concerned the examination of pus which came from a tuberculous 
 abscess of the kidneys. Inoculation with this pus had given a positive result, 
 therefore infectinus germs must have been present in the same. We shall 
 speak of this case later and give explanation for the negative result of the mic- 
 roscopic examination. 
 
 4. — Scrofulous Glands. 
 The scrofulous glands which I have examined I owe for the most part to 
 Privy Councillor Badeleben, who placed the same at my disposal directly after 
 they were removed. Twenty-one cases ia all were examined in which the 
 glands showed themselves tuberculous. I understand by this the presence of 
 epithelioid cells which are grouped in herds and enclose more or less numer- 
 ous giant cells. With few exceptions, in which a necrosis and caseous degen- 
 eration of the diseased gland tissue had not yet appeared, these cells were 
 
ETIOLOGY OF TUBBECULOSIS. 41 
 
 joined directly to the caseous herd present, and formed the immediate surround- 
 ing of the same. Only in glands which possessed a tuberculous structure of 
 this sort could tuberculous bacilli be proved. In a mimber of cases, en the 
 contrary, in which the glands were enlarged, partly also softened, and thor- 
 oughly impregnated with herds of pus, but in which epithelioid and giant cells 
 as well as the characteristic necrosis of the tissue were wanting, no bacilli were 
 found. 
 
 The tuberculous or scrofulous glands examined belonged to twenty-one 
 different patients. Of these eleven were between the ages of ten and twenty 
 years, seven between the ages of twenty and thirty, one each thirty-seven, 
 thirty-nine, and three. The glands had been situated fifteen limes on the neck 
 and in the submaxillary region, three times in the back of the neck, twice in 
 the axilla, and once in the region of the cubitus. In the last case, that of a 
 three-year-old boy, there existed at the same time caries of the wrist on the 
 same side. In three cases there had been a relapse after the first operation, 
 and this had caused a second excision of the glands. In several cases it was 
 stated that phthisis was hereditary in each family. 
 
 In general the tuberculous glands in reference to their contents of tuber- 
 culous bacilli were very uniform. In the interior of the caseous herd I have 
 found the bacilli only in two cases, and even here only individual specimens. 
 Tlie bacilli appeared only exceptionally and individually between the epitheli- 
 oid cells. On the contrary, among the giant cells there were always some, oc- 
 casionally many, which contained one or two tuberculous bacilli. Giant cells 
 with alarger number of bacilli, as one so often finds them in bronchial and mcs- 
 entric glands, I have never been able to find in scrofulous glands. 
 
 In the three cases in which after a time a second gland extirpation took 
 place, the glands twice showed themselves to have the same constitution as in 
 the first examination. The third of these cases, which is noteworthy in other 
 respects, was as follows : strongly built man of thirty-four years. A year 
 before large gland tumors had grown on the neck and in both axillae, and at 
 the same time a high degree of anaemia had developed. In the lungs no tu- 
 bercles could be shown. The tumors which had been excised had the figure 
 and size of potatoes, were of a soft, almost marrow-like constitution, and with- 
 out caseous changes in the interior. The microscopic investigation showed 
 that in the swelled mass numberless little herds of epithelioid cells were im- 
 bedded, which contained in their midst one or more giant cells. In many cf 
 these giant cells one or at most two tuberculous bacilli were found. Very rarely 
 it occurred that one bacillus was situated in the interior of an epithelioid cell, 
 close beside the nucleus of the same. Scarcely a year after the removal of these 
 glands, almost equally large tumors have developed themselves anew on the 
 same spots. These were extirpated again and showed the same microscopic 
 conduct, only with the exception that the number of bacilli-bearing giant cells 
 had decidedly increased in comparison with the previous tumors. 
 
 5 — Tttbeeoulosis of the Joints and Bones. 
 
 There were examined by me thirteen tuberculous joints, three hip joints, 
 five knee joints, three elbow joints, one foot joint, and one finger joint ; further, 
 
42 JETIOLOGY OF TUBEEOtJLOSlS. 
 
 ten tuberculous affections cf the bone, thus divided : three times on wrist bones, 
 five times on ankle bones, twice vortex caries (of these last in one case only the 
 pus was examined). To a great extent I owe this material for examination to 
 Privy Councillor Bardeleben. 
 
 The granulation-tissue which is formed in the surroundings of tuberculous 
 joints and bones offers no essential difference in the single cases. The same 
 appearances repeat themselves constantly in the structure of the tissue and in 
 the arrangement of the bacilli, and resemble completely the dsscription given 
 of scrofulous glands. One finds just the same more or less scattered and often 
 confluent herds of epithelioid cells which surround giant cells, and also here 
 the occurrence of bacilli is confined almost exclusively to the giant cells. In 
 the caseous, nucleusless spots, as well as in the pus secretions, the attempts to 
 find scattered bacilli only succeeded in some cases. Also in this respect tu- 
 berculosis of the bones and joints conducts itself exactly like that of the scrofu- 
 lous glands. 
 
 The bacilli could be proved in all the cases. Only in the abscess pus coming 
 from the vortex caries was it impossible to find tuberculous bacilli. But in- 
 oculation with this pus, as was formerly mentioned of the pus of a tuberculous 
 abscess of the kidneys, gave a positive result. 
 
 6. — Luptjs. 
 
 According to the anatomical investigations of Friedlaender and the positive 
 results of inoculation which Huter and Schiiller have obtained, it was to be 
 expected that lupus must also belong to the group of genuine tuberculous 
 diseases. I therefore used the opportunity offered to me by Director Hahn, 
 Prof. Kuster and Prof. Lewin, soon after the publication of my first commu- 
 nication concerning the setiology of tuberculosis, to examine a number of cases 
 of lupus in order to gain certainty in regard to this supposition. 
 
 Seven cases of lupus were investigated, which all had the most decided 
 symptoms and were watched for a long time in ths hospital, so that no doubt 
 of the correctness of the diagnosis can be entertained. From four cases I 
 received excised pieces of the skin, from the other three cases lupus substance 
 scraped out. For direct microscopic examination only the excised p'.eces of 
 skin were suitable. In all four cases, though only a few specimens in each, 
 tuberculous were found, only, however, in the interior of giant cells. The 
 tuberculous bacilli are so scattered in tlie lupus tissue that in two cases the bacilli 
 were notfound until from one twentj'-seven sections, from the other forty-three 
 sections had been examined. Nevertheless, it happened repeatedly that when 
 in a succession of sections not a single bacillus showed itself, sections followed 
 each other quickly with from 1 — 3 bacilli. More than one bacillus I have never 
 seen in a giant cell in lupus. 
 
 It may for the present be remarked here that of all the seven eases, inoc- 
 ulations were made into the anterior eye-chambers of rabbits, which without 
 exception produced tuberculosis of the iris, and in those animals which were 
 allowed to live for a longer time, general tuberculosis. In these tubercles re- 
 sulting from inoculation numerous tuberculous bacilli were found. From one 
 case (excised piece of skin from tlie cheek of a ten-year-old boy suffering from 
 
.STIOLOGT or T0BEECU.LOB1S. 43 
 
 lupws hypertrophieus) success was obtained in getting renicultnren of bacilli, 
 which have also been used for the successful inoculation of animals. 
 
 B.— TUBERCULOSIS IN ANIMALS. 
 
 By the study of the appearances under which tuberculosis runs its course, 
 in the various sorts ol animals, the noteworthy fact is manifest that tuberculosis 
 conducts itself differently in the case of almost every species. However striking 
 this fact at first appears, it nevertheless corresponds to the observations made 
 in regard to other bacteria diseases. So inflammation of the spleen in a similar 
 manner is different in different animals ; septiciimie of mice, conditioned upon 
 very small bacilli, offers another example, for when it is inoculated it kills 
 mice, but in rabbits only causes an erysipelas-like disease confined to the 
 skin. 
 
 Until now no warm-blooded animal is known which is entirely unrespon- 
 sive to the infection of the tuberculous virus, and one may therefore ejpect 
 that many varieties will show themselves in the anatomical aspect of tubercu- 
 losis in the various species of animals. 
 
 However various the forms which the symptoms of tuberculosis may take 
 in single species, and however little one may be inclined to explain human 
 phthisis and a tuberculosis of a guinea pig caused by inoculation as the same 
 sort of disease, nevertheless between these extremes there are found, partly in 
 the same species, still more in other species, transitional forms of tuberculosis 
 which cause the apparent gulf to vanish. But the complete unity of the tubercu- 
 lous processes of different species of animals shows itself to be irrefutable wlien 
 we look away from the constitution of the tuberculous organs as seen by the naked 
 eye, and from the secondary changes in the same, sucli as caseous degeneration 
 and calcination, and keep to the primary structure of the tubercle, which, as we 
 have already seen, repeats itself with typical regularity in all the various proces- 
 ses in man, and equally so in the apparently so different forms of tuberculosis i a 
 the various species ol animals. The diiferences in the tuberculosis of different 
 species of animals which most attract the eye concern only those secondary 
 changes whicli in the one case lead to wide-spread coagulation-necrosis wi h- 
 out caseous degeneration (liver and spleen of guinea pigs); in another to rapid 
 softening and the formation of a thinly liquid, pus-lilie secretion (tubercle of 
 the monkey); further to transformation into hop-like caseous substance (tuber- 
 cul'sis of man); to simultaneous calcination and caseous degeneration (pearl 
 distemper of cattle); to the formation of hard swollen masses with deposited 
 lime " concrcmenten " (tuberculosis of the fowl)— and so forth. The primary 
 changes in all these cases are histologically exactly alike. Somewhat the same 
 is true in regard to the formation of pus in various animals. So the pus formed 
 in consequence of a simple inflammation in the rabbit and the fowl has an en- 
 tirely different constitution than that of man, and yet in this case one would 
 not speak of different sorts of pus formation. 
 
 It would lead too far if the special peculiarities of every single kind of 
 animal should be described in detail, and I shall therefore be obliged to confine 
 myself to a brief characterizing of the different forms. 
 
44 ETIOLOGY OF TUBERCULOSIS. 
 
 r. — ^Pbelstjoht of Cattlb. 
 
 The tuberculosis of cattle runs its course, as is well known, almost always 
 by tlie forming of little knots which do not really become caseous and perish, 
 but become calcareous and heap themselves together in such masses that they 
 can finally form great tumors. Bat beside these there occur widespread firmly 
 caseous infiltrations cf the lung tissue, as well as hollow spaces in the lungs, 
 filled with pap-like caseous masses. 
 
 Of the last mentioned form only four cases were examined. The caseous 
 contents of the cavities were of such a consistence that when the cavities were 
 cut the contents could bo pressed out in sausage-shaped masses. The cavities 
 themselves appeared to have proceeded from enlarged bronchiae. In their 
 walls were found quite numerous giant cells, and in a number of these last 
 one to several tuberculous bacilli. The caseous masses were, as the inoculations 
 performed with them showed, infectious, yet no bacilli could be found in them. 
 On the places where the " bronchi-ectalischen" cavities approached the 
 surface of the lungs, the usual knot-shaped tumors of the " perlsucht " were 
 found on the pleura, and showed the immediate connection with this form of 
 cattle tuberculosis. 
 
 Of this last form eleven cases were exaniined in which the development of 
 the knots of the " perlsucht" did not confine themselves to the lungs, but 
 reached out to the diaphragm, psritoneum and omentum. Several times the 
 mesenterial glands were tuberculously changed and impregnated with firm 
 caseous herds. The tuberculous bacilli were wanting in no case, yet here 
 their number was extraordinarily fluctuating. In some cases only comparatively 
 few bacilli, and those exclusively in the giant calls of the ' ' perlsucht " knots, 
 were found, similarly as in scro!ul3us glands, and in the already mentioned 
 caseous (cheesy) herds in the lungs of cattle. I am, therefore, not able to share 
 the often-expressed opinion that " perlsucht " knots, in contract with the tub- 
 ercles in man, are always rich in bacilli. Besides such cases as run their 
 course slowly and always show very few bacilli, there are those in which 
 permanently or only temporarily the number of bacilli may be very consider- 
 able. 
 
 Also, in the same lung bacilli may be found to be very numerous in some 
 spots and very scarce in others. Sections prepared from large and hard, 
 therefore older knots contained often only scattered bacilli in giant ce'.ls. 
 The younger knots, on the contrary, showed themselves extraordinarily rich 
 in bacilli and allowed the recognition of the formerly mentioned relations 
 between bacilli and giant cells with great ease. 
 
 Besides tliis, bacilli are found between the small cells in such numbers 
 that in places they give the specimen a bluish color. 
 
 The caseous mesentric glands of cattle suffering from "perlsucht", which 
 I received for examination, were always extraordinarily rich in bacilli. The 
 bacilli were, on the contrary, less numerous in the ragged " perlsiichtigen " 
 luxuriant growths, permeated with many little hard knots and taken from the 
 pericardium of a beef -creature and also in the knots, which in such a case had 
 their seat in the kidneys. In all thcnumberof cases of "perlsucht " examined 
 amounted to seventeen, and the bacilli were wanting in none of them. 
 
ArlOLOGY OF TUBEEODLOSIS. 
 
 4:6 
 
 '4. — Ttjbeeoulosis of the Hoesb. 
 Four cases, of which, to be sure, I could not obtain all the organs, were 
 examined, nevertheless it could easily be seen that tuberculosis of the horse 
 lakes a middle place between that of cattle and the same disease in man. In 
 places the tuberculous formations on the peritoneum and omentum bore the 
 greatest resemblance to the " perlsucht "-knots of cattle, while in the same 
 cases and simultaneously, the lungs were permeated with extraordinarily nu- 
 merous miliary tubercles, which give them, on the surface of the section com- 
 pletely, the appearance of a human lung supplied with miliary tubercles. In 
 one case the way in which the tuberculous virus had gotinto the course of the 
 blood led to miliary tuberculosis. Namely, the retroperitoneal glands were, 
 changed into a very large tumor permeated with firm yellowish caseous herds, 
 which partly enclosed the vena cava inferior and formed uneven protuberances 
 towards the interior of the ven . Sections through this gland mass, and espe- 
 cially through the knots reaching into tlie vena cava, exhibited extraordinary 
 numbers of tuberculous bacilli, partly free, partly filling the numerous giant 
 cells. Several of the knots were softened on their surface and had plainly 
 mingled many tuberculous bacill with the blood of the vena cava. The mili- 
 ary tuberculosis had, therefore, arisen here in the same manner as it has been 
 shown by Weigert to arise in man. 
 
 Also, in the other cases of tuberculosis in horses, tuberculous bacilli could 
 be proved in the knots from the omentum and peritoneum, in the immensely 
 enlarged bronchial glands, and in the tuberculous knots of the lungs, spleen 
 and liver ; and moreover, here and there they were discovered in great 
 numbers. 
 
 3. TtTBEEOULOSIS OF THE PiG. 
 
 This appears to occur comparatively very often. Especially there are often 
 found in the pig, caseous changes in the lymph glands of the neck which are 
 of a tuberculous nature. In four cases in which I received such glands for 
 examination, tuberculous bacilli were found each time, partly free, partly in 
 giant cells. Besides this there occurs in a pig a peculiar form of caseous pneu- 
 monia, in which large parts of the lung are lobularly infiltrated with greyish- 
 red to greyish-yellow colored masses and are almost completely empty of air. 
 ' I have examined five cases of this form. The alveoli were here and there filled 
 with dense heaps of tuberculous bacilli. In other places the bacilli had already, 
 forced themselves into the surrounding tissue and bacilli-bearing giant cells 
 had formed here. In two cases one or even several bacilli -bearing giant cells 
 frequently showed themselves free in the alveolar spaces. It here concerned 
 itself plainly in all these cases of caseous pneumonia about a tuberculosis aris- 
 ing from the aspiration of considerable masses of bacilli. In one case the still 
 fresh infection of the lung appeared to have proceeded from the tonsils, which 
 were changed into deep ulcerations provided with a caseous base and also con- 
 taining tuberculous bacilli. Once I received pieces of muscle from a nig, which 
 were impregnated with numerous little knots for the most part calcareous. 
 These proved themselves under microscopic examination to be tuberculous ; 
 they contained giant cells, supplied with tuberculous bacilli. 
 
46 ^tlOLOGY OF TUBEBCtTLOSIS. 
 
 4. — Ttjbbhoulosis of the Goat and Shkbp. 
 I only once had opportunity to examine a lung of a sheep supplied with 
 tuberculous knots and the bronchial glands belonging wilh it partly caseous 
 and calcerous. The lung tubercles contained giant cells, with not very numer- 
 ous tuberculous bacilli. In the bronchial glands the bacilli were present more 
 abundantly. One case from the goat was also at my disposal, which, to be 
 sure, had special interest, in so far that a cavity almost as large as a fist had 
 formed in the right as well as in the left lung, and furnished the proof that 
 under some circumstances a condition completely analogous to human phthisis 
 can be developed in animals. The cavities were partly filled with caseous pus. 
 Their inner wall was sinuous, raw and fringy. Numerous giant cells with 
 tuberculous bacilli were found in the enclosing tissue ; single bacilli could also 
 be shown in the purulent contents of the cavities. Besides this, the lung tissue 
 in the surroundings of the cavities and for a pretty wide space was impregnated 
 with miliary tuberculous knots, which were also provided with bacilli-bearing 
 giant cells. Some largish knots in the spleen and liver, as well as the greatly 
 enlarged and caseous bronchial glands, showed the same behavior. 
 
 5. — TUBBEOULOSIS OF THE FOWL. 
 
 This is usually endemic and not seldom destroys all the fowls of a yard. 
 More or less rough, sometimes also perfectly smooth tumors are found in the 
 intestines and liver of the diseased animals. These tumors are as large as peas 
 or walnuts. In one of the cases examined one knot in the liver even reached 
 the size of a little apple. These tumors are of a compact constitution, show 
 themselves spotted whitish and yellowish on the intersection, and on the yellow 
 spots are partly calcareous. In one case tuberculous knots of almost the size 
 of a hemp-seed were present in the marrow of the bone of the long tubes 
 (riihren). All these knots, which belong to four different creatures, were ex- 
 traordinarily rich in tuberculous bacilli, these heaping themselves especially in 
 the immediate surroundings of the calcarous parts. In the knots situated en 
 the intestines the tuberculous bacilli could be followed into the villi intestina- 
 lis, and it is hence not improbable that they found their entrance to the inner 
 organs from the intestines, especially also as once only scattered little knots 
 were found in the lungs. On the other hand, it may be concluded from this 
 result, that the bacilli can get into the contents of the intestines, be excreted 
 with these and give rise to further infection, just as is the case in intestinal 
 tuberculosis in man. 
 
 TUBEEOULOSIS OP THE MoNKET. 
 
 In the case of the monkey tuberculosis acts differently, iii several respects,! 
 from the tuberculosis in man. It does not usually remain confinedlong to one 
 organ, but at an early stage spreads itself over the whole body. Then it does 
 not appear in the form of numerous little knots, which have an equal size, as 
 in human miliary tuberculosis, but leads to the formation of a larger or smaller 
 Lumber of tuberculous herds, whose size is very varying and which contain, 
 especially lu the liver, spleen and glands, instead of the firm caseous substance 
 of the tuberculosis in man, a rather thinly fluid pus, s > that they rather maV.e 
 
^ETIOLOGY <IF T0BEEGULO8I8. i"! 
 
 the impression of multiple abscesses than of tubercles. Beside these, to be 
 sure, the typical forms of the grey tubercle with the yellowish centre occur 
 in the lungs, on the pleura and the omentum. But these are also of various 
 sizes and one gains the impression that the spread of the tuberculous virus in 
 the monkey does not take place all at once, as in miliary tuberculosis in man, 
 but is continuous and only in small quantities. 
 
 The number of tuberculous monkeys examined by me amounts to eight. 
 In all these the disease had risen spontaneously, and apparanlly the first infec- 
 tious herd still existed in the lung. Only in one case had the tuberculosis 
 proceeded from the cavitas navium. An abscess had formed in tlic nasal duct, 
 which was probably caused by a wound from a scratch at the entrance of the 
 nose, and had spread constantly but slowly farther upon the septum and the 
 turbinated bones. The submaxilary lymph-glands swelled and became puru- 
 knt. Not until then did the previously active andstrong animal have trouble 
 in breathing and become emaciated. In the dissection very numerous tubercles 
 of varying size were found in the lung, spleen, liver and omentum. 
 
 In all the cases the tuberculous bacilli could be proved, and, moreover, 
 in the tubercles of the most different organs. Nevertheless the number of 
 bacUli was not very large. 
 
 7. — SpONTANBOUS TUBBEOTJLOSIS OF GuiNEA PiGS AND RaBBITS. 
 
 Among many hundred rabbits and guinea pigs, which were bought for 
 experimenlal purposes, were experimentally used and were finally dissected, 
 there was not a single animal which was tuberculous. Not until af ler the 
 attemp' s at infection with tuberculous substances had begun and a large num- 
 ber of tuberculous animals found themselves in separate cages, but in the same 
 room with other animals, single cases of spontaneous tuberculosis occurred 
 among the latter. Nevertheless plainly visible symptoms of tuberculosis hardly 
 ever showed themselves in such animals until they had spent three to four months 
 in a room with tuberculous animals. It was a very characteristic appearance 
 also, that when the number of artificially infected tuberculous animals decreased, 
 the cases of spontaneous tuberculosis became correspondingly rare ; the 
 reverse being also true. For a considerable time, when only very few tuber- 
 culous animals were kept in the space used for such experiments, the spon- 
 taneous tuberculosis among the other very numerous guinea pigs and rabbits 
 ceased entirely. The changes which were found in the animals dying from 
 spontaneous tuberculosis distinguish themselves from those caused by artificial 
 infection in a very characteristic manner, so that the varying methods of in- 
 fection can be recognized with all certainty. There were regularly in animals 
 dying with spontaneous tuberculosis one or more large tuberculous herds in 
 the lungs, which were far advanced in caseous degeneration and at the same 
 time decidedly enlarged and caseous bronchial glands. A few times larger 
 herds were wanting in the lungs, only the bronchial glands were extraordinarily 
 large and filled with caseous contents. The tuberculous changes had made 
 in the other organs comparatively little progress. 
 
 The artificially infected animals conducted themselves differently according 
 as they were infected by subcutaneous inoculation or by the inhalation of 
 
i8 MnoLOdY ov tubeecUlostS. 
 
 bacilli-bearing liquids. Usually the inoculation took place in one side of the 
 belly, and the lymph-glands situated next to the point of inoculation were 
 found considerably swollen and caseous. The bronchial glands, on the con- 
 trary, were almost always so small that they could scarcely be found. Also 
 in these cases the liver and spleen had undergone the greatest tuberculous 
 changes, while the tubercles in the lungs were still comparatively small. In 
 Ihu cise of animals infected by inhalation, which had always taken consider- 
 ab'e numbers of bacilli into the lungs, there were found corresponding to this, 
 not one or a few great herds, but a very large number of little tubercles in the 
 lunga. If one considers these experiences gained from artificially infected 
 animals, then he will be obliged to represent to himself the spontaneous tuber- 
 culosis, as it occurred under the above mentioned circumstances in guinea pigs 
 and rabbits, as having arisen through inhalation of one or more infectious germs, 
 that is bacilli. 
 
 Of this sort of spontaneously-diseased animals I have examined seventeen 
 guinea pigs and eight rabbits, among them a wild rabbit, which, as the only 
 one of ten animals of the same sort, died after three months' imprisonment, 
 tuberculous in a high degree. These all had many, in some cases indeed ex- 
 traordinarily numerous bacilli in the surroundings of the caseous herds of the 
 lungs. In the secondarily arisen tubercles the number of bacilli was usually 
 less. It seems tome worthy of mention, that many times, in the larger caseous 
 herds of the lungs, the central dissolution was very far advanced, and in con- 
 sequence of the same complete cavities, though of slight extent, had formed. 
 Up to a certain degree spontaneous-inhalation-tuberculosis brings on conditions 
 in these animals which are analogous to those of human phthisis. The infec- 
 tion only does not remain long enough localized, it spreads too early to other 
 regions of the body and leads thereby to the death of the animal before import- 
 ant cavities can form as they occur in the human lung. 
 
 Tuberculosis of the remaining organs takes a very peculiar course in both 
 the rabbit and the guinea pig, and moreover a different one in each. In the 
 beginning, in both sorts of animals, the tuberculous knots in the liver and 
 spleen have the usual characteristic appearance which they maintain in the 
 lungs. They are miliary, gray looking little knots, with yellowish centre, and 
 of a quite compact consistence. In guinea pigs the spleen is decidedly enlarged, 
 and of a blackish-red color, on which background the grayish knots show 
 very plainly. Very soon, however, the tubercles become confluent and there 
 arise larger whitish gray islands. These too increase constantly and give the 
 spl.en a light grayish-red and b'.ackish-red marbled appearance. Finally the 
 light parts get the upper hand, and the spleen can then take a wholly unusual 
 appearance, which does not in the least suggest the origin of this condition in 
 tuberculosis, especially when it comes to little ruptures and hemorrhages in 
 the fragile spleen-substance, by which it gets a still gayer coloring. At all 
 events it is very peculiar that tuberculosis in the spleen of the guinea pig leads 
 to such widespread " congulation-necrosis," but never to genuine caseous de- 
 generation, while in the lymph-glands of these animals a decided caseous de- 
 generation occurs. The liver of the guinea pig acts in an exactly similar 
 manner. In the first place gray disseminated knots form, lighter parts appear, 
 
MTIOI.OQY OF TaBERCULOSIB. 49 
 
 which increase, become confluent, and become intensely yellow in color. The 
 liver increases enormously in size, and finally looks marbled, with spots of 
 yellow and brown. In the darker parts of the liver there are usually still fresh 
 grey little knots to be seen. 
 
 In the dissection of a guinea pig tuberculous in a high degree, beside the 
 lungs permeated with little grey knots, the spleen, immensely enlarged and 
 marbled with light grey and blackish-grey, and the liver also decWtdely enlarged 
 and marbled in brown and yellow, attract the eye, and it gives a total which can 
 be mistaken for no other disease occurring in these animals. By the micro- 
 scopic investigation of a spleen or liver so changed it is shown that in tha 
 ligh colored parts no nucleus coloring occurs ; the cells have died and indeed 
 a sort of " coagulation-necrosis " is present. A large part of the organ is dead, 
 but no further dissolution occurs, the organ keeps its form and has only 
 changed its color. In these dead masses usually only scattered bacilli are to 
 be found. Only in single cases I have seen a peculiar increase and arrange- 
 ment of the bacilli in the necrotic liver tissue, of which I will speak later. The 
 bacilli occur more or less numerously on the border of the necrotic parts, and 
 are then frequently enclosed by giant cells. 
 
 In the kidneys of guinea pigs I have never observed tubercles visible to the 
 naked eye. 
 
 In rabbits the spleen and liver also appear enlarged, though in a far less degree 
 than in guinea pigs. In this animal the tubercles always remain small and in- 
 significant in the organs named, and there are never such changes as were described 
 in the case of guinea pigs. On the contrary, the kidneys are almost always sup- 
 plied with a number of whitish knots, which grow to the size of peas. In these 
 knots the tuberculous bacilli are usually found in abundance, and mostly arranged 
 in nests. Sometimes also I have found urethree which were filled with bacilli. 
 
 8. — Aetifiolaily gbnbrated Tuberculosis in Animals. 
 
 Artificially generated tuberculosis conducts itself in general just like that 
 which arises spontaneously. It takes also the form characteristic of every special 
 species of animals, and in fowls, for example, leads to the development of com- 
 pact, knotty tumors on the intestines and the liver ; in rabbits to the formation of 
 small gray tubercles with yellowish centre in lungs and spleen, and larger whitish 
 knots in the kidneys ; and in guinea pigs causes the considerable enlargement of 
 the spleen and liver, together with the peculiar gray or yellow marbled coloring 
 of these organs. 
 
 Of course the various sorts of infection condition certain differences in the 
 course of the tuberculosis in the form of the pathological changes. It is of the 
 greatest significance whether the infection was brought about with very few bacilli 
 or with greater numbers of them. The distinction conditioned upon this may be 
 studied most simply in the eye of the rabbit. Namely, if as few bacilli as possible 
 be put into the anterior eye-chamber there arise first separate little gray knots, 
 genuine miliary tubercles, which become yellowish in the centre. Their number 
 increases gradually, they finally become confluent and not until after a consider- 
 able time do they lead to the general caseous degeneration and destruction of the 
 eye as well as to the appearance of tubercles in other organs. When, on the con- 
 
50 ETIOLOGY OF TUBEECUL08IS 
 
 trary, from the beginning an abundant number of bacilli is introduced into the eye- 
 chamber, the first step is not the formation of single little knots, but the same 
 appearance is manifest which has already been cursorily mentioned in the descrip- 
 tion of lung phthisis as diffuse caseous infiltration, after the aspiration cf substances 
 rich in bacilli. Also in this case the eye becomes diffusely caseously infiltrated, 
 perishes very quickly, and the general infection, the appearance of many little 
 gray knots in the spleen and lungs, takes place very early, usually after three 
 weeks. 
 
 Almost the same distinction in the effect of infectious masses poor or rich in 
 bacilli is manifest when the same are put into the abdominal cavity of guinea pigs ; 
 the one time disseminated tuberculous knots of the peritoneum aud omentum with 
 slow progress of the process, the other time considerable thickening, shrinking, 
 and caseous degeneration of the omentum, together with a diffused infiltration of 
 the peritoneum, with numberless tuberculous knots of the smallest kind. 
 
 The relations are still different when the bacilh are brought directly into the 
 course of the blood, when they reach the lungs in considerable quantities by inha- 
 lation, or when the infection occurs only from a small wound on some part of the 
 body. In each of these cases the first stages of the changes must correspond with 
 the mode of infection used in each case. 
 
 But in its further course the disease always takes the type of tuberculosis. 
 Especially, the secondary tuberculous knots arising at a distance from the original 
 spot of infection always bear one and the same character. They are in the begin- 
 ning little gray knots consisting of herds of epithelioid cells, contain giant cells 
 and tuberculous bacilli exactly like the tuberculous knots arising spontaneously, 
 from which they are in no wise distinguished. 
 
 A special description of the conduct of the tuberculous bacilli in artificially' 
 generated tuberculosis is therefore not needed, and I can limit myself to the sum- 
 mary enumeration of the cases examined. These concern 373 guinea pigs, 105 
 rabbits, 3 dogs, 13 cats, 3 German marmots, 10 domestic fowls, 13 pigeons, 28 
 white mice (variety of the house mouse), 44 field mice (arvicola arvalis), 19 rats. 
 
 In these animals tuberculous bacilli were found in the tubercles without ex- 
 ception. On account of the great number of animals it was, to be sure, not pos- 
 sible to examine all the organs provided with tubercles in every separate case, and 
 I have been obliged in most cases to prove the presence of bacilli by crushing and 
 spreading out some tuberculous knots from the lungs or spleen on covering 
 glasses. 
 
 If, now, the result of the microscopic investigation of tuberculous objects, 
 as it has been minutely described in the above, be summarized, we have the fol- 
 lowing results : 
 
 In all those disease processes which, by their course as well as by their char- 
 acteristic microscopic structure and the infectious qualities of their products, must 
 be considered as genuine tuberculosis, there occur regularly in the tuberculous 
 herds staff-shaped forms, whose presence can be proved with the help of special 
 methods of coloring. This is the case as well in tuberculosis of man as in that of 
 animals of the various sorts. Also the number of single eases which generally and 
 specially were examined for the individual forms of tuberculosis is large enough 
 to maintain that here the question is not one of an occasional but of a constant 
 
jEllOLOGY OF TUBBKCULOSIS. 51 
 
 appearance, and thut therefore tuberculous bacilli are among the component parts 
 typical of the tubercles and their products. The two single cases in which bacilli 
 were not to be found concern the microscopic investigation of the pus of a tuber- 
 culous abscess of the kidneys and the pus from the abscess of a vortex caries. That 
 the bacilli were really wanting in these cases can nevertheless not be maintained, 
 because here just such products of tuberculosis were examined as are almost regul- 
 arly to be found without bacilli, owing to the fact that those originally present 
 had vanished, as has been shown in the other examinations. Without doubt bacilli 
 would have been found in these cases also if the original spots from which the pus 
 came could have been examined. 
 
 On the contrary, until now, however manifold the examinations of the most 
 various disease processes in men and animals, the bacilli peculiar to tuberculosis 
 liave never been found in other diseases. Where this has been said to be the case 
 the statements have proved themselves erroneous, proceeding from a wrong use of 
 the methoas of examination. 
 
 A second important result is that the appearance of tuberculous bacilli marks 
 the beginning of the tuberculous process. They appear ] ust when the first changes 
 in the cell elements of the tissue are noticeable. Not until the tuberculous bacilli 
 are present do the heaps of epithelioid cells, the formation of giant cells, and the 
 especially characteristic caseous products arising from the perishing of these cell 
 elements, appear. Further, the presence and the number of the tuberculous bacilli 
 are in closest connection with the progress of the tuberculous process. For where 
 the tuberculosis bears a chronic character, only few and scattered bacilli are found; 
 where, on the contrary, it is making rapid progress, numerous and thickly heaped 
 bacilli are present ; and where the tuberculous process has come to a standstill or 
 has run its course, the bacilli vanish. 
 
 These three facts, namely, that the tuberculous bacilli occur regularly and ex- 
 clusively in tuberculosis; that they in time and place precede all the peculiar patholo- 
 gical changes of tuberculosis; and that their number and their appearance and disap- 
 pearance stand in direct relation to the course of tuberculosis — these facts allow us 
 to conclude with great probability that tuberculous bacilli are not an accidental 
 accompaniment of tuberculosis, but stand in an original connection with it. 
 
 Such far-reachmg consequences hang on the decision of thia question, that 
 one cannot rest in having brought it near to a solution, but must make the attempt 
 to decide it with undeniable certainty. Moreover, a further investigation of the 
 conditions of life and development of these parasites promised further important 
 light on the setiology of tuberculosis and on the ways and means of defending 
 humanity against this most destructive disease. 
 
 The only possibility of reaching this goal lay in taking the same way which 
 had approved itself for the investigation of other bacteria diseases. The tuberculous 
 bacilli must be isolated from the diseased organs, bred outside of the body in 
 " reinculturen " (pure cultures), their behavior in this way investigated, and 
 finally tuberculosis be artificially generated by such bacilli, freed from all admix- 
 ture with the disease products. 
 II.— ISOLATION AND REINCULTUREN OF TUBERCULOUS BACILLI. 
 
 It could be seen in advance that the obtaining of reinculturen of tuberculous 
 bacilli would bo attended with difficulties, and therefore from the beginning the 
 
52 ETIOLOGY OF TUBPIRCULOSIS. 
 
 method ot culture upon firm, transparent breeding ground was adopted, because 
 this is superior to all other methods of reinculturen in certainty and ease of man- 
 agement. "With reference to the principle which lies at the foundation of this 
 method, as well as in regard to its difference from other treatment, and the manifold 
 advantages which it offers, I would refer to the minute description of the same 
 given in the earlier pages of this paper. 
 
 At first it was attempted to grow the bacilli from crushed lung tubercles on 
 " nahrgelatine " (meat-water-pepton-gelatine), but without success. These at- 
 tempts had been made in the temperature of the room, because in greater heat the 
 gelatine becomes liquid and thereby loses all the advantages of a firm breeding 
 ground. Since it se^'med probable that the attempts failed because a temperature 
 of 20° C. was not sufficient for the growth of the bacilli, it was necessary to supply 
 another firm, and at the same time transparent, breeding ground, which should 
 contain all the component parts demanded for the nourishment of bacilli. Such 
 an one seemed to offer itself in stiffened blood serum. I had found in experiments 
 made for the purpose of sterilizing blood serum by repeated warming, according 
 to the method first given by Tyndall for hay-infusion, that the serum when warmed 
 for a considerable time over 65° C, remained stiffened and transparent. Such a 
 breeding ground can be exposed for a considerable time to temperatures which 
 correspond with the temperature of the body, without undergoing any changes. 
 Bacilli-bearing substances were spread out on such stiffened transparent blood- 
 serum, and left in a breeding apparatus at 37° C. The direct examination fre- 
 quently undertaken under slight magnifying power showed after some days the 
 appearance of peculiarly shaped colonies, which, as was recognized under astronger 
 magnifying power, and with the uso of color reaction, consisted only of tuberculous 
 bacilli. Nevertheless, before I proceed to the more exact description c f these ba- 
 cilli cultures, I have still to describe the preparation of the stiffened blood serum, 
 which in course of time has proved itself to be the most practical. 
 
 Even the flowing of the blood into the necessary vessels demands several pru- 
 dential measures. As vessels for catching the blood rather high cylindrical glasses 
 provided with a glass stopper are suitable. These are well cleaned, then washed 
 out with a one per cent, sublimate solution, in order to kill any bacteria germs 
 possibly clinging to them, and then washed again with alcohol to remove the sub- 
 limate. Then one lets the blood of the slaughtered animal flow immediately from 
 the cut into these purified vessels. Nevertheless it is well not to catch the blood 
 first flowing after the stab, because it carries away with it cut hairs and particles 
 of dirt from the skin and fur. The vessel should be filled nearly to the rim, closed 
 with a si opper and placed immediately in a refrigerator. As soon as the coagula- 
 tion of the blood begins the vessel must be kept perfectly still, as otherwise the 
 formation of a firm cruor would be disturbed and a quantity of red blood-corpuscles 
 would be mixed with the serum. The blood-filled vessels remain in the refrigera- 
 tor from twenty-four to thirty hours and even longer, until a good-sized layer of 
 completely transparent amber yellow serum has formed over the cruor. When 
 the serum is colored more or less Woody, then it contains too many red blood- 
 corpuscles and becomes opaque in warming. The serum is now filled by means 
 of a pipette into re-agent glasses wklch are provided with a wadding stopper. The 
 pipette as well as the re-agent glasses and the wadding stopper, are previously made 
 
AETIOLOGY OF TDBEKCUI-OSIS. 53 
 
 free from bacteria germs by heating them at least an hour at 150-160° C. in a double 
 ■walled heat ingbox made of sheet iron. One fills there-agent glasses about one-third 
 with serum, and closesthem immediately with a stopper made of cotton wadding. 
 In spite of all this care there are regularly found in the blood serum bacteria germs, 
 which come from the air, from the hair of the slaughtered animal, etc. , and would 
 very soon cause decay and decomposition of the serum if they were not destroyed. 
 Other liquids destined for the "reincultur" of bacteria can be sterilized, that is 
 made free from all bacteria germs, easily and certiinly by boiling. This cannot 
 be done in the case of blood serum, because by higher temperature it completely 
 loses its transparency. There remains, therefore, only the method adopted by 
 Tyndall in the sterilization of hay-infusion, that is, instead of heating it once to 
 a boiling temperature, to heat it repeatedly at a temperature of 55°-60°. The 
 bacteria, namely, if not spore-bearing, are easily killed in liquids even by a tem- 
 perature of 55°. The spores, on the contrary, as is well known, endure these 
 temperatures and do not die until the boiling point is reached. Once heating of 
 the liquid, therefore, only kills the spore-free bacteria and leaves the spores which 
 may be there untouched. In the medium so favorable to their growth, however, 
 the spores germinate soon, changing themselves into bacilli, and as such cannot 
 stand a temperature of 55° they are therefore killed by successive warmings before 
 they have had time to form new spores. But since the spores germinate at differ- 
 ent times, and often do not develop into bacilli until after several days, it is neces- 
 sary to repeat the warming. Experience has taught that it is almost always suf- 
 ficient to warm the blood serum for an hour for five successive days to free it 
 completely from germs which are capable of development. This warming can 
 take place in an open water bath. It is safer to use a tin vessel especially kept 
 for the purpose and which possesses double walls filled with water and a cover 
 constructed in the same manner, so that the warming shall be equal on all sides. 
 
 The blood serum sterilized in this manner is then stiffened, and in order to 
 get the greatest possible surface for inoculation the re-agent glasses should be held 
 inavery slanting position. Also tinboxeswith a double bottom and nglasscover, 
 placed in a slanting position, are practical for this purpose. The water in the 
 bottom of the glass is so heated that a thermometer lying in the box between the 
 re-agent glasses shows 65° 0. In this temperature the serum stiffens in from half 
 an hour to an hour. The serum of different animals is not uniform in its conduct. 
 The serum of sheep usually stiffens most quickly, calf serum most slowly. When 
 serum is warmed at a higher temperature, for example at 70°, it stiflfens far more 
 quickly, but it is then more difiicult to keep it transparent. A well-prepared blood 
 serum must be almost completely clear, transparent and amber-like. At most 
 only at the lower end of the re-agent glass and in the thickest layer may it be 
 whiter and less transparent. It must also not be too soft, but must almost have 
 the consistence of a hard-boiled hen's egg. 
 
 During the warming, usually on the upper cooler wall of the re-agent glass, 
 more or less steam condenses and forms drops which, when the re-agent glass is 
 taken up flow down and collect between the deepest part of the serum and of the 
 glass wall. A small part of the area of inoculation is covered by this liquid. Never- 
 theless the liquid is in so far of value that it takes up by diffusion soluble sub- 
 stances from the stiffened blood serum and is changed into a very good breeding 
 
54: iETIOLOGY OF T0BEKCUL08IB. 
 
 solution. When the bacteria to be cultivated are spread out upon the stiffened 
 serum, just up to the edge of this liquid, then they develop at the same time and 
 close by each other on the firm breeding ground and in the breeding liquid, so 
 that their special modes of growth in liquid and upon a firm substratum can be 
 immediately compared. 
 
 When the re-agent glasses provided with stiffened blood serum are preserved 
 for a length of time, since the wadding stopper does not prevent evaporation of 
 the moisture, a very gradual drying of the serum, progressing from above down- 
 wards, takes place, yet it occurs so slowly that for months a sufficiently large area 
 suitable for cultures remains at disposal between the upper dried part of the serum 
 and the lower part covered by the liquid. 
 
 When the sterilization of the blood serum has not succeeded, this shows itself 
 a few days after the stiffening, especially if the serum be put experimentally into 
 the breeding apparatus. In these cases little whitish points form which appear 
 singly or in larger numbers, and soon enlarge. Sometimes the blood serum becomes 
 liquid under the influence of such bacteria, then loses its clearness and becomes 
 covered with a whitish skin. Microscopic investigation shows that we here always 
 have bacilli which plainly have proceeded from spores germinating late. As a 
 matter of course, only such serum glasses may be used for " reinculturen " as after 
 several days' stay in the breeding apparatus show no trace of such impurities, but 
 remain completely clear and transparent. For many purposes, especially when it 
 is wished to examine the reinculturen directly with the microscope under slight 
 magnifying power, it is to the purpose to stiffen the serum in watch glasses or 
 other suitable vessels. Such vessels should have a glass cover as a protection 
 against the entrance of air germs. They are further placed in glass vessels which 
 are lined with moist blotting paper, and can so be exposed to the breeding temper- 
 ature. So sure a protection from inj urious impurities as the re-agent glasses closed 
 by wadding is, to be sure, not given by this arrangement, and reinculturen con- 
 tinued tlirough manyrepeated breedings of tuberculous bacilli are only to be carried 
 on by the help of blood serum stiffened in the re-agent glasses. 
 
 Just as great care as the preparation of the steriUzed stiffened blood serum 
 demands is absolutely necessary when the sowing is to be made on the prepared 
 breeding ground, if at the same time the entrance of foreign germs and the defile- 
 ment of the breeding ground by bacteria and fungi is to be prevented. 
 
 As to the material to be used for sowing, that Is naturally the most suitable 
 which contains many bacilli, is of a soft nature (that the bacilli may be spread as 
 quickly as possible), and is as fresh as possible, that is as free from the bacteria of 
 decay. When these latter are confined to the surface of the organ which is to serve 
 as a point of departure for culturen, it is still possible with certain precautions to 
 obtain reinculturen of tuberculous bacilli. But as soon as the foreign bacteria 
 have forced themselves into the deeper layers all attempts to separate the tubercu- 
 lous bacilli from them in culturen will be in vain, because the bacteria of decay 
 grow with extraordinary rapidity in comparison with tuberculous bacilli and 
 have taken possession of the entire breeding ground before the last have reached 
 a visible growth. 
 
 Also, when the sowing material contains very few bacilli and is of a firm con- 
 sistence, there are difficulties in causing the cultures to grow. In this case, namely, 
 
iETIOLOGT OF T0BEK0UL08IS. 55 
 
 the bacill-bearing substance cannot be so crushed that the bacilli can be spread out 
 free and upon the surface of the blood serum ; on this account they remain hidden 
 in the substance, develop there and the colonies growing in scanty numbers with- 
 draw themselves easily from observation. 
 
 The reinculturen succeed most surely when a tubercle rich in bacilli, or 
 richly tuberculous substance from the interior of a still slightly caseous lymph- 
 gland of a guinea pig killed for the purpose, be used for sowing. For this pur- 
 pose one should proceed in the following manner : A number of knives, scissors 
 and pincettes are so thoroughly heated in the flame that they are freed from all 
 bacteria clinging to them, and laid ready in such a manner that no impurities can 
 afterward get at them. In the mean time, the animal, which must just have 
 been killed, is spread out upon a dissecting board. In order, when cutting 
 through the skin to avoid dusting off particles of dirt, hairs, etc., the fur of the 
 animal should be thoroughly moistened with a one per cent, strong sublimate 
 solution. After this one cuts through the skin with the still hot scissors and with 
 the help of the still hot pincette, and lays it back on both sides so far that the 
 lymph-glands of the regio axillaris and inguinalis are completely free, but the 
 glands, if they are to be used for reinculturen, must not be touched with the in- 
 struments used in cutting the skin. With another hot pair of scissors another 
 piece, 1-3 qu. ctm. large, is cut out from the side wall of the thorax, and the 
 surface of the lungs laid bare. By this means a number of little tuberculous 
 knots are made accessible, from which, as quickly as possible, with still other 
 instruments, which must have been cooled for this operation, one or more are 
 prepared. In order to free the bacilli contained in the little knots, one cuts or 
 crushes these with the scissors or, still better, between two scalpels which have 
 been previously heated and cooled. The substance broken and rubbed to pieces 
 is then put into the re-agent glass, spread out upon the surface and rubbed with 
 a platinum wire which has been melted into a glass staff, and has Immediately 
 before using been heated and cooled again. The re-agent glass is to be held 
 slantingly or almost horizontally between the thumb and the forefinger, and the 
 wadding cork must be so held in the mean time with the other fingers of the 
 hand that impurities from coming in contact with other objects may not 
 reach it. The placing of the substance on the stiffened serum which, for the 
 sake of brevity may be called inoculation, must be done as quickly as possible in 
 order that the germS of foreign organisms from the air may not get upon the in- 
 oculating substance, or into the re-agent glass. It is also advisable to undertake 
 the experiment in a room in which no dust is stirred up, and moreover all un- 
 necessary motions which ould cause dust from clothes, etc., to get into the air 
 are to be avoided, since experience has taught that the germs of micro-organisms 
 cling to the particles of dust suspended in the air. 
 
 In spite of all these prudential measures the entrance of single foreign germs 
 is n'ot to be avoided with absolute certainty, and it is necessary in every single 
 case to inoculate several re-agent glasses, perhaps 5-10, that if the reincultur 
 does not succeed in the one or the other, the remainder may be free from all im- 
 purities. 
 
 In such manner as the preparation of lung tubercles for sowing has been de- 
 scribed, must the experiments be conducted when lymph-glands, tubercles of the 
 
56 ETIOLOGY OF TUBEECULOSI8. 
 
 spleen, etc., are to be used for culturen. One must always operate with instru- 
 ments that have been made red-hot, and these must be changed every time a new 
 layer is to be exposed. All preparatory cuts which do not touch the inoculating 
 substance itself are to be made with hot instruments, the inoculating mass on the 
 contrary to be cut out with cooled scissors and pincette. The constant change of 
 instruments is necessary in order that impurities which might attach themselves 
 to the instruments in cutting the skin and the superficial layers may not be car- 
 ried into the culturen. 
 
 When the organs of animals which have just died or just been killed were at 
 my disposal, and the sowing was carried on in the manner just described with 
 substances containing tuberculous bacilli, the reinculturen have succeeded with- 
 out exception. The result was, on the contrary, uncertain when the material 
 from human corpses or cattle suffering from " perlsucht " was used, since there 
 were always impurities on the surface, and it was moreover not wholly fresh 
 when I received it. In these cases I have first repeatedly and thoroughly washed 
 the surface of the object with one per cent, sublimate solution, then with con- 
 stantly changed, glowing hot instruments taken off the upper layers one at a 
 time, and cut the inoculating substance from a depth at which I could feel sure it 
 was free from foreign bacteria. In this manner I usually succeeded in obtaining 
 reinculturen from material of this sort, especially from little lung vomicae lying 
 near the surface whose covering was removed with hot instruments after treat- 
 ment with sublimate. 
 
 After the stiffened serum is inoculated with a bacilli-bearing substance, the 
 vessels are placed in a breeding apparatus and kept constantly at a temperature 
 of 37° C. Not every breeding apparatus is adapted to the culture of tuberculous 
 bacilli. The growth proceeds but slowly and the vessels must therefore remain 
 for weeks at a time in the apparatus. When the breeding apparatus, owing to 
 its construction, causes a rapid evaporation of liquid from the vessels, the serum 
 dries before the tuberculous bacilli have developed into visible colonies. Es- 
 pecially such apparatus as are unequally warmed, so that the steam always present 
 in them condenses on the cooler places, for example on the glass cover, and must 
 be constantly replaced by steam developed from the culturen vessels, cannot be 
 used. The Arsonval thermc staten are very practical ; the warmth is evenly di- 
 vided and the serum keeps almost unchanged in them. 
 
 In the first few days one will notice no change in the culturen in the breed 
 ing apparatus. If a change occurs, if whitish or even other colored drops or spots 
 appear on the surface of the serum, if these enlarge more or less quickly, be- 
 cloud the liquid in the bottom of the glass, or even liquefy the serum, this is a 
 sign that the cultur is not successful, and that foreign bacteria have forced them- 
 selves in and grown more luxuriantly than the bacilli. If one examines such 
 drops or spots he always finds them to consist of bacilli or micrococci which, un- 
 der Ehrlich's color treatment, always take a color opposite to that of the tubercu- 
 lous bacilli, and are distinguished from them in size and shape. 
 
 In those little glasses which have remained free from such impurities the first 
 suggestions of the growing colonies of tuberculous bacilli do not show themselves 
 until after ten to fifteen days. They appear as pale white little points or spots, 
 which lie on the surface of the serum, arc without lustre, and on that account 
 
ETIOLOGY OP TUBERCULOSIS. 57 
 
 show plainly against their moist surrouadlags. Tliey can best bo compared with 
 little dry scales which are slightly attached to the scrum surface. According as 
 the inoculating substance was rubbed upon a greater or less surface, and accord- 
 ing to the abundance of bacilli in the same, the scales develop in smaller or 
 greater numbers and extent on the serum surface. 
 
 The single scales only reach a limited spread, so that when only a few are 
 present they remain separated. When numerous and thickly crowded together, 
 on the contrary, they finally unite and form a thin, grayish white lustreless coat- 
 ing on the serum. 
 
 A very different image is presented by the culturen developing from substan- 
 ces wliich contain only scattered bacilli. As has already been suggested, one does 
 not succeed in such casesin freeing the bacilli by rubbing and crushing the sub- 
 stance, and spreading it on the surface of the serum. They remain, in the substance 
 and form there colonies which grow almost to the size of a poppy seed. In such 
 cases there can be no doubt that each single little colony proceeded from one sin- 
 gle, or at most two bacilli, because microscopic investigation has always found 
 only 1-2 bacilli in a giant cell of the tissue in question. Accordingly we can 
 also further conclude that, in the formerly mentioned examples, the single scales 
 developing upon the serum proceeded also from single bacilli. 
 
 If a beginning of reinculturen of tuberculous bacilli has been obtained in 
 the manner just described, they can be carried on without difficulty. For this 
 purpose some of the whitish scales can be put into a re-agent glass containing 
 stiffened serum by means of the platinum wire, which must be made glowing 
 hot and then cooled again, immediately before its use. By the use of this wire 
 the scales are also to be spread as much as possible on the serum surface, and 
 rubbed to pieces. In this second sowing far more numerous bacilli reach the 
 serum surface, and can there be spread more easily and evenly than was the case 
 with the original inoculating material ; in consequence of which one obtains in 
 this and later breedings, no longer single scales, but coherent, membrane-like 
 colonies. These take in general the figure which the motions of the platinum 
 wire prescribed beforehand in the sowing. They can therefore be laid on in lines, 
 either in a perpendicular or horizontal direction, or may take any figure one may 
 choose to construct on the serum. Vigorously growing cultures nevertheless 
 spread more or less beyond the original limits of the sowing. This spread is, 
 however, not the consequt nee of independent motions of the bacilli, which, as 
 already shown, they do not possess, but it takes place in consequence of the fact 
 that in the constant increase of the bacilli the increase of mass does not take 
 place in the diameter of the thickness, but in area. The growing bacilli d ) 
 not heap themselves upon each other, but have the tendency to spread out in 
 area and push the already formed coherent membrane away over the surface of 
 tlie serum. This is most marked when the bacilli membrane reaches the liquid 
 at the base of the re-agent glass. It does not penetrate into the liquid, but it 
 forces itself over the same and forms a fine cover on the surface of the liquid. 
 Very often indeed it presses up to a height of some millimeters on the opposite 
 side of the glass. 
 
 The bacilli "culturen " have other noteworthy qualities by which they may 
 be distinguished from other bacteria "culturen " by the naked eye. In the first 
 
58 .ETIOLOGY OF TrBKRCULOSIt. 
 
 place, they never liquify the serum, as some sorts of bacteria regularly do. They 
 do not penetrate into the scrum, but always remain on its surface and lie loosely 
 there. In consequence of this the membrane-like bacilli vegetation can be lifted 
 and washed away by tipping the re-agent glass so that the liquid at its base may 
 flow over the surface of the serum. Other bacteria possess a pap-like consistence 
 and let themselves mingle with the liquid, making them cloudy. This is not the 
 case with tuberculous bacilli. The thin membranes formed by them do not dis- 
 solve in the liquid, but in consequence of their firm consistence break into larger 
 or smaller lumps, which are washed away by the' liquid, and finally collect at the 
 bottom of the same. The peculiar stifif and brittle constitution of the colonies 
 shows itself best in the part of the " cultur" which covers over the liquid in the 
 re-agent glass. As soon as this liquid is set in motion the little skin on its sur- 
 face breaks into plates and lumps, which slowly sink to the bottom. The liquid 
 always remains clear, as well when the bacilli vegetation itself stretches over it, as 
 when by washing off of the serum surface masses of bacilli get into it, or when 
 in the beginning the inoculating substance is Intentionally put into it. From this 
 apoearance also we should conclude, as direct observation had already shown, that 
 the tuberculous bacilli possess no independent motion; for bacilli which can move 
 disperse themselves in all directions through the breeding solutions, and give them 
 a cloudy appearance. 
 
 Within certain limits, moreover, the conduct of the bacilli "culturen," as 
 seen by the naked eye, depends ujwn the consistence of the blood serum upon 
 which they grow. The firmer that is. the more the bacilli colonies have the coe- 
 Btitution just described. On a very soft gelatinous serum the development is 
 somewhat different. The distribution of the bacilli is not uniform because the 
 hard and firmly coherent masses of bacilli cannot be crushed on the soft serum in 
 the sowing. The inoculating substance therefore remains lying on the serum in 
 small detached crumbs. The grovrth of the colonies does not reach so uniformly 
 over the surface as on the firm serum, but leads to thicker compact masses which 
 cling firmly to the soft serum. Even when the serum is somewhat less soft, so 
 that the colonies begin to spread themselves out on the surface, one notices a 
 firmer attachment of the bacilli membrane to the serum area. One does not 
 then succeed in washing the membrane from the serum, or lifting it off with the 
 platinum wire, without at the same time loosening parts of the serum. 
 
 TVlien even the properties of the " culturen " noticeable with the naked eye 
 show a difference from other bacteria and admit a judgment as to their purity, 
 this is much more the case when they are examined under a moderately strong 
 magnifying power, such as is obtained with Zeiss' Objective System, A. A., ocular 
 4. wilh drawn out tube, ^SO fold magnifying power\ It is then seen that the 
 bacilli colonies form such peculiarly shaped figures as do no other sort of bacteria, 
 ilicroscopically of course these colonies can be noticed far earlier than with the 
 naked eye. Already five to six days after the sowing takes place and the " cul- 
 tur " has been kept at breeding warmth, peculiar, very dainty little figures appear 
 on the surface of the serum. These appear as fine lines, often bow- shaped. The 
 smallest have mostly the figure of an S. Longer colonies show the most manifold 
 serpentine turns and windings which often remind one of interlacing letters. 
 While the ends of these lines run off into sharp points, in the middle they are 
 
AETIOLOGY OIT TDBEECDLOSIS. S9 
 
 more or less swollen to a spindle shape, and the smaller younger colonies are ex- 
 tiaordinarily thin and delicate, the older thickcT and of heavier forms. Gradually, 
 by coutinued spreading and melting togelher, the windings take more and more 
 a plate-like form which, by the ware-like designs and the transition of their bor- 
 ders into the peculiar oscillating lines of the single colonies, allow their origin as 
 such to be recognized. Finally a number of such plates melt into cacli other, 
 and form the previously described membrane-like bacilli colonies, while the plates 
 proceeding from single colonies correspond with the whitish scales visible to the 
 naked eye. In order to examine the colonies directly under the microscope and 
 to follow their development, four-cornered little glass basins provided with a 
 glass cover are specially adapted. 
 
 That these colonies are only formed by the tuberculous bacilli is soon seen 
 when they are colored by Ehrlich's method, and examined by strong magnifying 
 power. This can be done most practically when one presses a covering glass 
 firmly to the surface of the serum covered with colonies and takes it up again. 
 Numerous colonies then remain clinging to the covering glass in their natural ar- 
 rangement and grouping, dry there and can be colored as was described formerly 
 in the directions for covering glass specimens. The bacilli are not thrown together 
 without method, but are placed with their axes of length parallel with the axis 
 of length of colony. It is striking that the bacilli do not touch each other, but 
 are separated, though only by slight spaces. As was formerly suggested, one 
 may conclude from this conduct that the bacilli are surrounded by a building 
 substance and are joined together by this, as is proved by the firm coherence of 
 the colonies. Very frequently in farther advanced colonies one finds all or 
 nearly all the bacilli spore-bearmg. 
 
 Usually the " cultureu " have reached the maximum of their development 
 after four weeks and then remain unchanged. The continuation of the same is 
 most practically carried on in intervals of from two to four weeks. Nevertheless 
 such " culturen " as have existed for months are still capable of development and 
 can be used for further breeding. By the method described in the above I have 
 gained a number of reinculturen of tuberculous bacilli from different materials, and 
 have continued them through a longer or shorter succession of breedings. Several 
 attempts at " culturen," and indeed the first which were made, proceeded from 
 guinea-pigs, which were tuberculously infected by inoculation from man aud from 
 various animals. Other " culturen " have been obtained directly from the original 
 tuberculous material. The reinculturen indirectly gained by the help of the orig- 
 inal inoculation of guinea-pigs relate to the following cases : 
 
 1. — Human lung-phthisis cultivated through twenty-two months, therefore 
 almost two years, in thirty-four successive breedings ; 
 
 3. — Human lung-phthisis (caseous mass from the lung) cultivated for two and 
 one-ha'f months in five successive breedings ; 
 
 3. — Human lung-phthisis (contents of the lung cavity) cultivated for three 
 months in six successive breedings ; 
 
 4. — Human miliary tuberculosis (tubercle of the lung) cultivated for seven 
 months in twelve successive breedings ; 
 
 5. — Human miliary tuberculosis (tubeicle of the pia mater) cultivated for 
 three months in fire successive breedings ; 
 
60 ETIOLOGY OF TUBERCULOSIS. 
 
 6.— Human miliary tuberculosis (tubercle of the spleen) cultivated for two 
 and one half months in four successive breedings ; 
 
 7.— Human tuberculosis of the uterus cultivated for four months in six surci-s- 
 sive breedings ; 
 
 8.— Human intestinal tuberculosis (caseous mesentric glands) cultivated for 
 six months in nine successive breedings ; 
 
 9._Human lung-phthisis (sputum) cultivated for four and one-half months in 
 seven successive breedings ; 
 
 10.— Scrofula in man (excised necl£-gland) cultivated for seven months in 
 twelve successive breedings ; 
 
 11.— Tuberculosis in monkey (lung-tubercle) cultivated for six and one-half 
 months in twelve successive breedings ; 
 
 12. —Tuberculosis in monkey (tubercle of the spleen) cultivated for seven 
 months in thirteen successive breedings ; 
 
 13.— Tuberculosis in monkey (caseous bronchial glands) cultivated for four 
 months in six successive breedings ; 
 
 14.— Tuberculosis of cattle (pleura knots) cultivated for three months in 
 five successive breedings ; 
 
 15.— Tuberculosis of cattle (pleura knots) cultivated for three and one-half 
 months in five successive breedings ; 
 
 16. — Tuberculosis of cattle (peritoneal knots) cultivated for twenty-one months 
 in twenty-nine successive breedings ; 
 
 17. — ^Tuberculosis of cattle (peritoneal knots) cultivated for three months in 
 five successive breedings ; 
 
 18. — Tuberculosis of cattle (knots from the diaphragm) cultivated for tour 
 months in six successive breedings ; 
 
 19. — Tuberculosis of cattle (pap-like caseous masses from the lung, first case) 
 cultivated for eight months in thirteen successive breedings ; 
 
 30. — Tuberculosis of cattle (pap like caseous masses from the lung, second case) 
 cultivated for three months in five successive breedings ; 
 
 21. — Tuberculous bacilli "cultur" (Nos. 1 and 5 breeding) cultivated for four 
 months in seven successive breedings ; 
 
 The following reinculturen were obtained directly from the tuberculous ma- 
 terial : 
 
 22. — Miliary tuberculosis from man (tubercle of the lung) cultivated for nine- 
 teen months in twenty-four successive breedings ; 
 
 23. — Miliary tuberculosis from man (tubercle of the lung) cultivated for six 
 months in ten successive breedings ; 
 
 24. — Lung-phthisis from man (contents of a cavity) cultivated for seven months 
 in eleven successive breedings ; 
 
 25. — Lung-phthisis from man (contents of a little cavity in the tip of lungs) 
 cultivated for eiglit months in ten successive breedings ; 
 
 26. — Lung-phthisis of man (contents of a closed cavity) cultivated for eight, 
 teen months in twenty-four successive breedings; 
 
 37. — Caseous pneumonia of man (lung-tissue) cultivated for five months in 
 seven successive breedings. 
 
 28. — Caseous pneumonia of man (lung tissue) cultivated for seven months in 
 nine successive breedings ; 
 
Etiology of tqueecctloSis. 61 
 
 29.— Scrofulous gland cultivated for six months in seven successive breed- 
 ings; 
 
 30.— Scrofulous gland cultivated for five months in seven successive breed- 
 ings; 
 
 31.— Scrofulous gland cultivated for three months in three successive breed- 
 ings;- 
 
 33.— Scrofulous gland cultivated for three months in four successive breed- 
 ings; 
 
 33. — Tuberculous testicles cultivated for four months in six successive breed- 
 ings : 
 
 84.— Fungous joint cultivated for fifteen months in nineteen successive breed- 
 ings ; 
 
 35. —Lupus cultivated for sixteen months in twenty-one successive breedings ; 
 
 36. — Lung from cattle-tuberculosis (caseous mass) cultivated for six months 
 in eight successive breedings ; 
 
 . — Lung from domestic animal tuberculosis (calcined knots) cultivated for 
 five months in seven successive breedings ; 
 
 38. — Knots from the diaphragm of a tuberculously diseased domestic animal 
 cultivated for nine months in fifteen successive breedings ; 
 
 39.— Knots from the pericardium of a tuberculously diseased domestic animal 
 cultivated for eighteen months in twenty-three successive breedings ; 
 
 40. — Caseous pneumonia of the pig cultivated for five months in eight success- 
 ive breedings ; 
 
 ' 41. — Spontaneous tuberculosis of guinea pig (knots from the lungs) cultivated 
 for six months in nine successive breedings ; 
 
 43. — Spontaneous tuberculosis of the guinea pig (spleen) cultivated for three 
 months in five successive breedings ; 
 
 43. — Spontaneous tuberculosis of the guinea pig (knots from the lung) culti- 
 vated for four months in seven successive breedings. 
 
 The preservation of the cultureu demands such an expenditure of time and 
 trouble, that always only a certain number can be maintained at the same time. 
 I let the most of them perish again as soon as their vegetative disease-producing 
 qualities had been sufiiciently established by a " culture " continued for several 
 months, and by the inoculations undertaken with it. Only the Culturen No. 1 
 (lung-phthisis). No. 16 (tuberculosis of a domestic animal), No. 23 (miliary tuber- 
 culosis). No. 26 (contents of a cavity from a phthisical lung). No. 34 (fungous joint), 
 No. 35 (lupus), No. 39 (tuberculosis of a domestic animal) have been continued 
 until now, and are to be further preserved in order to find out whether in the life 
 of the tuberculous bacilli continued outside of the animal body some sort of changes 
 may not occur in their qualities. It might appear strange that comparatively so 
 large a number of "culturen" were established, when a few would have sufiiced 
 for observing the conduct of the bacilli in the "culturen." Nevertheless in the 
 beginning it appeared to me by no means impossible, that although the bacilli of 
 the various tuberculous forms, — lupus, phthisis etc. — showed microscopically no 
 difEerence, the bacilli derived from the various sources might perhaps manifest 
 dififerences in the culturen. But in spite of the closest attention directed to this 
 point, I have been able to find nothing of the kind. Li the "culturen" also, 
 
G2 ETIOLOGY OF TUBEECrLOeiS 
 
 whether taken from miliary tubercles or from the contents of vomicae, often lupus, 
 often tuberculosis of domestic animals, the tuberculous bacilli have been com- 
 pletely uniform in their conduct. In no way has a change made itself noticed in 
 the " culturen " continued for a longer period, between sixteen and twenty-two 
 months. If I formally made the claim that the culturen of tuberculous bacilli 
 possess especially characteristic properties, by means of which the tuberculous 
 bacilli could be distinguished from other bacteria, almost with greater certainty 
 and certainly with more important grounds than by means of their tinctorial qua- 
 lities, I can in confirmation of this claim appeal to a very rich amount of examined 
 material. There were, namely, after the favorable properties of the stiffened blood 
 serum were recognized, numberless attempts made, partly from reinculturen of 
 various bacteria, partly from the sowing of the most various animal substances on 
 blood serum, but vegetations which resembled the culturen of tuberculous bacilli 
 never appeared. These attempts belonging, to be sure, to other experimental 
 investigations, form counter-attempts, from which we see that the above described 
 characteristic cultures are only to be obtained from substances which contain tu- 
 berculous bacilli. 
 
 It must still be of special significance for aetiology to determine whether the 
 tuberculous bacilli can grow and multiply under conditions which make possible 
 to them an existence independent from the body of man and of the animals. For 
 the decision of this question it was first necessary to examine whether the bacilli 
 only grow on the stiffened blood serum or whether they also flourish in other 
 nourishing media. Attempts with liquid sterilized blood serum gave the result, 
 that little particles of bacilli-culturen, which were put on the surface of the serum 
 in a re-agent glass, developed themselves in the way already described, just as on 
 the surface of the liquid beside the stiffened blood serum, and formed a thin whit- 
 ish coating, which was of a fragile, brittle consistence, and which broke in moving 
 the serum and sank to the bottom. The scrum always remained clear. 'When I 
 did not succeed in keeping the sowed substance floating on the surface of the 
 serum, when it sank into the liquid, the result was no noticeable increase of the 
 sowed pieces. 
 
 The blood serum of various sorts of animals showed, as well in a stiffened as 
 in a liquid condition, no essential difference in the power of serving as breeding 
 ground for the tuberculous bacilli. They appear, to be sure, to flourish best on 
 the serum of sheep, cattle and calves. But the serum of horse and swine blood 
 gives very vigorous culturen. Even on the serum of dogs blood the culturen do 
 not grow noticeably less vigorously, in spite of the fact that this species of animals 
 is quite resistent to tuberculosis. On the contrary, tuberculous bacilli do not grow 
 on the white of eggs. At first I did not succeed in bringing about the growth of 
 tuberculous bacilli in other liquids than blood serum. When one or more crumbs 
 of a culture were put into a glass with neutralized meat-broth, the crumbs certainly 
 appeared in the course of four or five weeks to have increased somewhat in size, 
 but it was difficult to decide whether a real growth had taken place. Not until I 
 had broken the pieces of the bacilli-culture and rubbed them fine, put them into 
 the meat-infusion and by frequent shaking dispersed them through it, that an un- 
 deniable development took place. It does not appear to be unimportant for the suc- 
 cess of this attempt, that the culture should be placed in glass alembics -with a broad, 
 
ETIOLOGY OF TUBERCULOSIS. 63 
 
 level base— so-called Erlenmeyer alembics— and only so much liquid put into the 
 alembic as that the bottom be covered from one half to at most the depth of a cen- 
 timeter. The meat-infusion always remained clear, but in the course of four or Ave 
 weeks a flne-grained sand-like looking white layer formed at the bottom of the vessel. 
 The single little grains, which had probably grown from the scarcely visible par- 
 ticles of the sowed substance, consisted exclusively of tuberculous bacilli. 
 
 If one compares this conduct of the cultures in liquid nourishing media, 
 namelv their slow growth and the constant clearness of the liquid, with the reports 
 of former culture attempts from Klebs, SchuUer, Toussaint (who noticed after from 
 one to three days a cloudiness of the culture-liquid) one cannot resist the convic- 
 tion that these cultures could not have been reiuculturen. 
 
 Also in regard to the meat-infusion the phenomenon is repeated, that the flesh 
 of various animals and even of such as are only slightly susceptible to tuberculosis 
 — as dog, cat and domestic mouse — allow the cultures to develop in almost equal 
 strength. It is to be mentioned that neutralized meat-infusion stiffened by an ad- 
 dition of Chinese gelatine, and thereby changed into a firm breeding ground, which 
 can be exposed to the breeding temperature without becoming liquid, also gives 
 a breeding ground for tuberculous bacilli cultures. This is, to be sure, considerably 
 inferior to the stiffened blood serum, because on the slippery surface the bacilli can 
 not be spread out well, and in consequence of this the characteristic membranous 
 cultures are not developed, but instead compact, irregular masses. Since some 
 disease-producing bacteria — for example inflammation-of-the-spleen bacilli, typhus 
 bacilli, glanders bacilli and erysipelas micrococci — grow very vigorously on veget- 
 able substances — for example especially on boiled potatoes— attempts were made 
 in this direction with tuberculous bacilli also, but they have led to no positive results. 
 All in all, therefore, no great scope is offered the tuberculous bacilli in regard to 
 breeding ground. 
 
 There are similar limitations with regard to a second condition essential for 
 the existence of bacteria, with the limits of temperature within which growth takes 
 place. 
 
 In often repeated attempts it resulted that in a temperature of 43° C. in the 
 course of three weeks no growth took place. Further, in 30° C, the development 
 is very slight and ceases completely between 28° and 39° C. The cultures thrive 
 best in a temperature of 37° to 38" C. A considerably wider range of tempera- 
 ture, within which they can increase, stands at the disposal of other disease-pro- 
 ducing bacteria. The inflammation-of-the-spleen bacilli, for example, grow very 
 luxuriantly between 20° and 24° C, and form spores in a short time. They can 
 thrive also up to 43"' 0. If we take into consideration that the anthrax-bacilli can 
 run the entire course of their development to spore formation in twenty-four to 
 forty- eight hours, in a temperaturewhich in summer isoftenreached by the surface 
 of the ground, and that they can do this on dead vegetable substrata, the supposi- 
 tion is justified that they can run their course of development in suitable places 
 out of doors and independently of the animal body. No further explanation is 
 necessary to show that, owing to this, the aetiology of anthrax takes an altogether 
 different shape than if the anthrax-bacilli in their existence were dependent alone 
 upon the animal body. The same would hold good of the tuberculous bacilli, if 
 they could grow on breeding substrata such as occur in nature and if they could 
 
64 JSTIOLOGY OF TUBEECULOSIS. 
 
 develop and form spores in a comparatively short time in a temperature correspond- 
 ing to summer warmth. But this is not the case. The lowest limit of tempera- 
 ture in which the tuberculous bacilli are able to growisnot reached by the summer 
 temperature ; also, the growth of these bacteria goes on so slowly that they would 
 be crowded out by the much more quickly developing sorts of bacteria everywhere 
 appearing before they had finished their course of development. Even if, there- 
 fore, other more easily obtainable substrata than those of an animal nature were 
 found, which could serve the tuberculous bacilli as breeding ground, nevertheless 
 the last mentioned reasons would speak decisively against the supposition that the 
 tuberculous bacilli could lead an existence independent of the animal organism. 
 We are, therefore, compelled, so far as our experience reaches, to consider the tu- 
 berculous bacilli not as bacilli which can grow anywhere, but as genuine parasites, 
 that is such as can find the conditions of their existence only in the animal f r 
 
 human organism. 
 
 D.— ATTEMPTS AT INFECTION. 
 
 These attempts until recently have formed the most important part of the 
 experimental investigations concerning tuberculosis. But although these have 
 been carried on in a very extensive manner, they lack, except in a few instances, 
 the prudential measures which must necessarily be united with them to make them 
 free from objection. 
 
 There are three sources of error which can raise a doubt in regard to the 
 attempt at infection. First, mistaking spontaneous tuberculosis for the tuberculosis 
 artificially created by infection. Second, the mistaking of products of genuine tuber- 
 culous disease for pathological changes, which with the naked eye or even microscop- 
 ically, more or less resemble them. Third, unintentional infection with tuberculous 
 virus by means of infected instruments, inoculating material, etc., in short through 
 the neglect of antiseptic prudential measures. How shall one protect hi msclf against 
 these sources of error ? To avoid the errors arising from spontaneous tuberculosis, 
 it has been suggested that one experiment only with those animals in which tuber- 
 culosis seldom or never occurs. But since animals in which no spontaneous tu- 
 berculosis occurs are always more or less indisposed to this disease, and therefore 
 furnish no reliable reagent for the effect of the tuberculous virus, this proposition 
 is practically not feasible. Also for attempts in anthrax infection one would, for 
 example, not chose for exclusive use dogs, which, as is well known, are almost 
 exempt from this disease; but, on the contrary, experiment with animals which 
 are as sensitive as possible to anthrax-infection. The same holds of attempts at 
 infection with tuberculosis. The more sensitive, therefore, a kind of animal is to 
 infection with tuberculous virus, so much the better it is adapted to the infectious 
 attempts in question. Nevertheless only under the condition that one succeeds 
 in keeping the artificial and the spontaneous infection separate in the animals used 
 for experiment. With some little attention this is r.ot so diiBcult. The charac- 
 teristic marks by which the two are to be distinguished have already been given 
 in detail. It is self-evident, however, that, even though by means of these charac- 
 teristics spontaneous tuberculosis be excluded as a caiise of mistake, all prudential 
 measures should be taken to confine the spontcneous disease to ns narrow a field 
 as possible. This may be attained by separation of lie tuberculous animals in 
 difEerert cages, by frequeut airing, cleaning and disinfecting of the stalls. Never- 
 
ETIOLOGY OF TUBEECUL08IS. 65 
 
 theless it is not advisable permanently lokeep rabbits and guinea pigs in the same 
 rooms that contain tuberculous animals; they would scarcely remain free from 
 tuberculosis longer than eight to ten months in infected stalls. In one case a 
 number of animals were kept as long as possible by way of experimenting on their 
 immunity, but in spite of the best care only here and there one remained free from 
 tuberculosis for more than a year, and even these a few months later also became 
 victims to the disease. After all these experiences, all the numerous experiments 
 in which tuberculosis was conclusively shown, have little or no force as proof 
 unless the product Itself should make manifest that a spontaneous tuberculosis 
 exists or can be excluded. 
 
 As to the second source of mistake, the confusing of non-tuberculous knots 
 with genuine tubercles, nothing is simpler than to exclude the same. The genuine 
 tubercles are infectious and contain tuberculous bacilli ; the false do not. Even 
 if one will not admit the diagnostic worth of tuberculous bacilli, one must distin- 
 guish between infectious and non-infectious knots. Therefore, if by an attempt 
 at infection, for example if by the inhalation of any substance, some little grey 
 knots be caused in the lung of a dog, one may not content himself with this simple 
 result, and resting upon this claim that these are genuine tubercles. Under all 
 circumstances the infectious nature of such little knots must be proved. Where 
 genuine tuberculosis is concerned one is generally spared the trouble of especially 
 proving their infectious nature by inoculation with the knots, for in this case the dis- 
 ease seldom shows itself confined to one spot; almost always it has already attacked 
 other organs of the body, itself furnishing proof of its infectious nature by its prop- 
 agating ability. Therefore, when the formation of tubercles stretches itself out 
 past the original infectious spot into the lymph glands, lungs, liver and spleen, it can 
 without further proof be considered infectious. If, as is, for example, the case after 
 the inhalation of non- virulent firm particles into the lungs, and after the injection 
 of granular masses into the " bauchhohle " (belly cavity) in the peritoneum, the knots 
 caused by this remained confined to the place of infection (here the lungs and 
 peritoneum) and show no inclination to further infection of the body, then this 
 circumstance speaks against the inference that genuine tubercles exist here, and 
 special proof of their infectious nature must be furnished. If this is not done, as 
 it, in an incomprehensible manner, has not been in several of the newer investiga- 
 tions undertaken to prove the non-infectious nature of tuberculosis, then the real 
 proof is lacking in the experiment. 
 
 The third mistake mentioned, the unintentional infection by means of instru- 
 ments, etc., appears to have clung to almost all former investigations with regard 
 to tuberculosis to a greater or less degree, whether such investigations were directed 
 towards proving or disproving its infectious nature. And yet this mistake may 
 be avoided without great difficulty if one holds to the rules concerning anti- 
 septic operations, and above all things carefully disinfects the instrument for 
 every single attempt. All metal instruments, such as scissors, pincers, knives, 
 inoculating lancets, must be heated thoroughly. Special care is demanded in 
 the treatment of the syringes used for injection. Syringes, of ordinary con- 
 struction cannot be disinfected with sufficient certainty, because they do not 
 admit a high degree of heat without being injured, and liquid means of dis- 
 infection, as shown by experience, do not certainly destroy the infectious 
 
QQ ETIOLOGY OF TDBEECULOSIS. 
 
 material in the interior of the syringe and especially that clinging to the punctur- 
 ing apparatus. Hence the syringes must have a special construction which makes 
 their disinfection by heat possible. For this purpose the syringe must be made 
 of glass and metal. The lower end of the same must be made to have an air-tight 
 connection with the framework of the needle by means of a cork plate, set 
 in and bored through ; and the piston must be wound with a soft cotton thread. 
 In this form the syringe can, before every experiment, be made free from infec- 
 tious germs by an hour's heating at 150° to 160" C. The piston is then moistened 
 by absorbing boiled distilled water, and if the enwrapping is done with some care, 
 it becomes as tight ashy the use of the ordinary leather or gutta percha piston.* 
 The hands of the experimenter are to be disinfected with a one percent, sublimate 
 solution, and of course everything else is to be avoided which could lead to an 
 unintentional infection of the animal to be experimented on during or after the 
 operation. 
 
 By all the attempts at infection to be mentioned in what follows, the pruden- 
 tial measures just explained were strictly carried out and, therefore, to speak again 
 of the latter, for every attempt several freshly bought animals were used and kept 
 in separate cages, the effect of the infection was proved so early, that a confusion 
 with the later appearing spontaneous tuberculosis could not occur ; further, the 
 tuberculous changes appearing in consequence of the infection were always studied 
 with reference to the presence of tuberculous bacilli, and where it seemed neces- 
 sary, also especially with reference to their infectious qualities. The infection 
 itself took place with antiseptic precaution and especially with reliably disinfected 
 instruments. 
 
 The attempts at infection carried out in the course of my investigations re. 
 garding tuberculosis fall into two groups. To the one group belong those attempts 
 in which tuberculous bacilli-bearing parts of tissue were used ; to the second, those 
 m which reinculturen of tuberculous bacilli were the infectious material. 
 E.— ATTEMPTS AT INFECTION WITH TUBERCULOUS BACILLI- 
 BEARING TISSUES. 
 
 These served partly for studying the effects of the products of various sorts 
 of tuberculous processes, partly to gain suitable sowing-material for the beginning 
 of reinculturen. As inoculating material there were used pieces of tissue from 
 various organs of human miliary tuberculosis, from phthisic lungs, various forms 
 of localized tuberculosis, from fungous joints, scrofulous glands, lupus, tuberculosis 
 of various animals. The inoculating material was always examined with reference 
 to its contents of tuberculous bacilli. The inoculation took place in this manner : 
 In guinea pigs a small cut was made with the shears into the belly and by the use 
 of the points of the shears a pocket-shaped subcutaneous wound about one half 
 ctm. deep was made in this cut. Into this little skin pocket a little piece of the 
 inoculating substance, varying in size from a grain of millet to a mustard-seed, 
 was pushed in as deeply as possible. On the following day the inoculation wound 
 always appeared closed and showed no reaction. Usually a noticeable swelling 
 of the lymph-glands lying next to the point of inoculation, usually of the inguinal 
 glands on one side, first appears after two weeks and at the same time a harden- 
 
 •Syring'^s of ttiia construction are furnished by H. Windier, court instrument maker, 
 Berlin, N. W. Dorotheenstrasse 3. 
 
iETIOLOGY OF TnHEE0trjL0SI8. 67 
 
 ing and knot-forming showed itself upon the up-to-that-time completely healed 
 inoculation-wound. After this the enlargement of the lympli-glands increased 
 rapidly, often to the size of a hazel nut. The knot at the point of inoculation then, 
 mostly broke out and covered itself with a dry crust, under which was aflat abscess 
 not discharging much pus and provided with a caseous base. The animals then 
 began to grow emaciated, to have rough hair and difliculty in breathing and died 
 usually from the fourth to the eight week, orwere killed within this period. Also 
 in the case of rabbits the inoculating substance was a few times put into a pocket- 
 shaped sldn- wound. But since the course of the disease did not run so precisely 
 and so quickly after the subcutaneous inoculation as was the case with guinea pigs, 
 I afterwards chose the anterior eye cliamber as the point of inoculation in rabbits. 
 The course of the iris-tuberculosis arising in consequence of this inoculation has 
 been described often and therefore does not need a special description. The fol- 
 lowing inoculations were carried out in this manner: 
 
 1. Miliary tuberculosis. — Tuberculous knots of the pia mater, very rich in 
 tuberculous bacilli : six guinea pigs. Of these one died in five weeks, two in six 
 weeks, two in seven weeks after the inoculation. The sixth was killed in the 
 eighth week. In all the animals the lungs, liver and spleen were tuberculous in a 
 high degree and the inguinal glands were caseous. 
 
 2. Miliary tuberculosis. — Grey little knots of the lung, quite rich in tuber- 
 culous bacilli : six guinea pigs. Three died in the sixth week, the others were 
 killed a few days later. All tuberculous as in No. 1. 
 
 3. Miliary tuberculosis. — Grey yellow knots from the spleen and kidney, 
 not very rich in tuberculous bacilli : six guinea pigs. Died in the sixth and seventh 
 week. All tuberculous as in No. 1. 
 
 4. Miliary tuberculosis. — Grey knots of the lung, quite rich in bacilli : three 
 guinea pigs. Two died in the sixth, one in the seventh week. All tuberculous 
 as in No. 1. 
 
 5. Miliwry tuberculosis. — Grey knots of the lung containing few bacilli ; 
 five guinea pigs, two rabbits at the " root of the ear." One guinea pig died after 
 eight weeks, the others were killed a few days later. All tuberculous. The rabbits 
 killed after ten weeks had caseous lymph-glands at the root of the ear and on the 
 neck, quite a number of grey little knots in the lungs and some knots in the 
 kidneys and in the spleen. Five guinea pigs were inocalated with tubercles from 
 the spleen of one of the guinea pigs. Of these three died in the eighth week, the 
 other two were killed in the same week and all found tuberculous. Further, the 
 caseous gland substance of the rabbits rubbed in water, was injected into the belly 
 cavity of two rabbits. "When these animals were killed eight weeks later, tuber- 
 culosis of the omentum, spleen and liver existed as also quite a number of grey 
 knots in both lungs. 
 
 6. Caseous prieumonia and tuberculosis of the brain-membranes.— Two 
 guinea pigs with the bacilli-rich lung-substance, one guinea pig with a piece of 
 the tuberculously infiltrated and bacilli-rich pia mater. The animals died in the 
 fifth and sixth week. Both tuberculous. 
 
 7. Oaseously infiltrated lung.— &ix gmaea, ^\gs. The first died after six 
 weeks. The others were already Very sick and were killed on the following day. 
 All tuberculous. 
 
68 ETIOLOGY OF TTJBEECULOSIS. 
 
 8. PhtAisio lung with vomicoB, intestinal abscesses and caseous mesentric 
 glands. — With the contents of one vomica, which contained quite a number of 
 bacilli, two guinea pigs were inoculated, and four with the very bacilli-rich sub- 
 stance of the mesentric glands. The last died in the course of the fifth and sixth 
 weeks, of the first two one died in the sixth week, the other was killed a few days 
 later. All tuberculous. 
 
 9. Caseous hroncMtis and intestinal tuberculosis. — With the moderatelr 
 bacilli-rich lung substance, five guinea pigs were inoculated. Two of them dieU 
 in the eighth week ; the others were killed before the end of the sarhe week. 
 All tuberculous. 
 
 10. A phthisic lung containing vomicae. — With thickened luog tissue which 
 contained a few bacilli, four guinea pigs were inoculated. Of these, three died 
 in the seventh and eighth weeks, the last not until the twelfth week. All tuber- 
 culous. 
 
 11. Phthisic sputum. More or less bacilli-rich sputum freshly taken from 
 three different sufferers from phthisis was inoculated at different times into nine 
 guinea pigs. The animals died, part before the eighth week, the others were 
 then killed. They were all tuberculous. 
 
 12. Phthisic sputum, dried for two weeks : — Three guinea pigs. Two died in 
 sixth week, third was then killed. All tuberculous. 
 
 13. Phthisic sputum, dried for two months. — Three guinea pigs. Killed 
 after five weeks and found wilh tuberculosis in lungs, liver and spleen. 
 
 14. Tuberculosis of the uteius and "■tuben." — Caseous substance from the 
 tuben inoculated into six guinea pigs. Two animals died after seven weeks. 
 The others were killed in nine weeks. All tuberculous. 
 
 15. Pus from a tuberculous abfcess of thehidneys. — Two guinea pigs were 
 sub- cutaneously inoculated with it, and two suffered an injection into the cavity 
 of the belly. The animals were killed after five weeks. In the guinea pigs sub- 
 cutaneously inoculated, the inguinal glands were swollen and beginning to be 
 caseous ; in the enlarged spleen were numerous, in the lungs few, little grey knots. 
 Theinjected guinea pigs had many tuberculous knots on the peritoneum and in 
 the omentum ; spleen more strongly tuberculous than in the inoculated animals, 
 a'so larger and more numerous tubercles in the lungs. 
 
 16- — Pus from a cmgestion-abscess occasioned by aortex-caries. — Five guinea 
 pigs received from it an injection inlo the belly cavity. The same boiled distilled 
 water which served for thinning the pus was injected into the belly cavity of one 
 guinea pig which served as cootrol-tbier (animal to prove whether association 
 with infected animals would give the disease). This animal was left in the same 
 cage with the others. The animals were killed in the seventh week. The " con- 
 trol-thier " had not a trace of tuberculosis either in the belly cavity or in the 
 lungs. The animals into which the pus was injected showed a remarkably fine 
 tuberculosis of the peritoneum and of the omentum, besides this also a more or 
 less advanced tuberculosis of the spleen and lung. 
 
 VI ■ — Fungous elbov-joint—Bahsiwacc with very few bacilli inoculated into 
 four guinea pigs. Killed in the tenth week. All tuberculous. 
 
 'L%.—Scrtfulous glands iiomWiTee different cases inoculated into ten guinea 
 pigs at different times. The inoculating substance contained few bacilli and cor- 
 
2ETI0L0GY OP TUBERCULOSIS 69 
 
 responding with this the tuberculosis ran its course much more slowly. Never- 
 theless also in these animals, the swelling, the first noticeable symptom of 
 disease, and the later caseous degeneration of the inguinal glands, leave no doubt 
 that the place of inoculation formed the point of entrance for the tuberculous 
 virus. Four of the animals died from the tenth to the twelfth week, the others 
 were then killed. In all the lymph glands in the neighborhood of the place of 
 inoculation were caseous, and the spleen, liver and lungs tuberculous to a marked 
 degree. 
 
 1^.— Scrofulous gland. — The gland substance, poor in bacilli, transferred into 
 the anterior eye chamber of four rabbits. In all four animals in the course of the 
 third week, tuberculosis of the iris began to develop and lead to caseous degener- 
 ation of the bulbus. In the tenth week the rabbits were killed and beside the 
 destruction of the bulbus, caseous degeneration of the neck lymph-glands and 
 numerous grey knots were found in the lungs. 
 
 20. — From five different cases of lupus eighteen rabbits were inoculated in 
 the anterior eye-chamber. The course of the disease corresponded exactly with 
 that described in No. 19. An iris-tuberculosis at first developing slowly, grad- 
 ually leading to caseous degeneration and suppuration of the bulbus and finally 
 to general tuberculosis. The inoculation was without results in the case of one of 
 the rabbits. Some were killed just when the iris-tuberculosis had developed, 
 others after the swelling and caseous degeneration of the neck-glands had ap- 
 peared ; still others finally died with wide-spread tuberculosis of the lung, liver, 
 spleen and kidneys. As well in the tubercles of the iris as in the tuberculously 
 altered glands, lungs, etc., tuberculous bacilli were proved more or less abun- 
 dantly. From a sixth lupus case three guinea pigs, and from one of the above 
 mentioned cases five guinea pigs were subcutaneously inoculated. In these 
 animals also there were swelling and caseous degeneration of the inguinal glands. 
 They died in the seventh to the eighth week after the inoculation, were tubercu- 
 lous in a high degree, and had numerous tuberculous bacilli* in the lungs, spleen, 
 liver and kidneys. 
 
 31. Lunff affected ly ^' perlsucM" partially calcareous knots with quite 
 numerous bacilli, inoculated into eight guinea pigs. These died within five to 
 eight weeks and were all tuberculous in a high degree. From one of these guinea 
 pigs four others and from a second three others were inoculated. Of these ani- 
 mals also five died in the sixth and seventh week, the last two were killed in the 
 eighth week. In all these also tuberculosis was found. Further : From the 
 "perlsucht" lung used in these attempts, a cat was inoculated and died after seven 
 weeks, tuberculous. A second cat inoculated with lung tubercles from this ani- 
 mal after six weeks appeared emaciated and short-breathed. She was killed and 
 found to have numerous tubercles in the lungs and spleen. 
 
 33. — A '^ perlsucht'''' knot from the peritoneum inoculated into six guinea 
 
 *Lately Demme, Pfeifer and Dontrelepont have made communioations relating to the 
 occurrence of tuberculous bacilli in lupus-skin and in the tubercles of animals inoculated 
 with lupus. My investigations in regard to lupus, which include not only the proof of ba- 
 cilli in lupus skin and in inoculation tubercles, but also long continued ' ' rein-culturen " of 
 lupus-bacilli and successful inoculation undertaken with them, had been concluded for 
 several months, when those communications were published, so that these could have had 
 no manence upon my work. 
 
70 JETIOLOGY OF TUBEKCUJL0S18. 
 
 pigs. Three of them died in the fifth and sixth weeks, the others were killed 
 some days later. All tuberculous. 
 
 23. PerUucht knot from thi lung, partly with caseous contents, and not 
 very rich in bacilli. Seven guinea pigs. Five of them died up to the seventh 
 week. The last two were killed in the eighth week. All tuberculous. 
 
 24. Calcareous perUucM knot from t?ie peritoneum with many bacilli. 
 Three guinea pigs ; these died up to the sixth week. AH tuberculous. 
 
 25. Caseous pneumonia o/;?!"^'.— Thickened, very bacilli-rich lung tissue. 
 Five guinea pigs. These died in the fifth and sixth week and were tuberculous. 
 
 26. From the lung tubercles of a rabbit which died of spontaneous tubercu- 
 losis, four guinea pigs were inoculated. Two of these died in the seventh week, 
 two were killed in the eighth week. They were all tuberculous. Four guinea 
 pigs were again inoculated from the first of these animals, two guinea piga and 
 four rabbits from the second, two rabbits from the third, and one guinea pig and 
 one rabbit from the fourth. The guinea pigs were inoculated subcutaneously, the 
 rabbits in the anterior eye-chamber. The guinea pigs died up to the seventh week 
 of tuberculosis, the rabbits all were attacked with iris-tuberculosis ; two died in 
 the ninth and tenth week of tuberculosis, the others were then killed and more or 
 less lung tubercles were found in them. 
 
 27. Two guinea pigs and two cats were inoculated with lung tubercles from 
 a monkey, which died of spontaneous tuberculosis. The two guinea pigs died in 
 the sixth week, one cat in the seventh, the other after thirteen weeks. All tuber- 
 culous. Six guinea pigs and one rabbit (in the anterior eye-chamber), were then 
 inoculated from one of the guinea pigs and these were all found to be tuberculous 
 before the eighth week (partly died, partly killed). Finally from two animals of 
 this second group the tuberculosis was reinoculated into seven other guinea pigs 
 with success. Also from one of the cats four guinea pigs were successfully inoc- 
 ulated. It is still to be mentioned that four guinea pigs were inoculated with the 
 spleen of this monkey, which had been dried fifty-six days and with the lung 
 tubercles of the same, which had lain fifty-seven days in absolute alcohol. These 
 animals for four months showed no change, were then killed and proved them- 
 selves free of tuberculosis. 
 
 28. From a second monkey wliich died of spontaneous tuberculosis two 
 guinea pigs were inoculated with lung tubercles and died of tuberculosis in the 
 eighth and ninth weeks. Further : from these guinea pigs two guinea pigs and 
 one rabbit were inoculated. As these appeared already diseased in the sixth 
 week, they were killed and found tuberculous. Two guinea pigs were inoculated 
 with lung tubercles of the same monkey which had been dried and preserved 
 three days. These animals were also killed in the sixth week and found tuber- 
 culous. 
 
 These experiments in inoculation which have just been enumerated were 
 made upon one hundred and seventy-nine guinea pigs, thirty-five rabbits and four 
 cats, and the inoculation had as a consequence tuberculosis in every case without 
 exception. Moreover the presence of tuberculous clianges did not confine itself 
 to single knots of a doubtful nature in one or the other organ, but ia every single 
 case the tuberculosis could be proved with all the certainty wished, first, by the 
 development of the characteristic symptoms of the disease, such as swelling of the 
 
-ETIOLOGY OF TDBKKGULOSIS. 71 
 
 glands, caseous ulceration of the point of inoculation, emaciation and difficulty of 
 breathing ; second, in dissection by the far advanced and very considerable patho- 
 logical changes proceeding from the point of inoculation into the neighboring 
 lymph glands and into the lungs, spleen and liver. Moreover, under microscopic 
 examination the characteristic tissue elements of the tubercle and the presence of 
 tuberculous bacilli was always proved. The manner in which the inoculation tu- 
 berculosis conducted itself in the different animals and in the different organs has 
 already been described in detail. 
 
 Other experimenters have had less favorable results from their inoculations 
 with tuberculous substance. On the other hand the regularly favorable results 
 obtained by me will appear less striliing when it is considered that I never used 
 material in which tuberculous bacilli could not be proved, and that for my inocu- 
 lations I always used those species of animals which are especially disposed to 
 tuberculosis. Besides this, the fact that the inoculations were carried out with 
 all possible care and exactness may have contributed not a little to the results. 
 One might consider it an omission that no attempts were made with the inocula- 
 tion of non-tuberculous substances. Nevertheless it did not appear to me neces- 
 sary to malce such attempts myself, because, during the course of my investi- 
 gations, inoculation with the most manifold substances containing no tuberculous 
 bacilli were made by the hundred in the same rooms, and moreover on guinea pigs 
 and rabbits, and a tuberculosis traceable to the inoculation was never found. 
 Especially was non-tuberculous material very often put into the anterior eye- 
 chamber and not a single time did tuberculosis of the iris result, while after the 
 inoculation with genuine tuberculous masses it never failed to appear. Besides, 
 the abortive inoculations made with the lung tubercles of the monljey, which tu- 
 bercles had been dried and preserved in alcohol, described in No. 27, form to a 
 certain extent such attempts, for plainly by the death of the bacilli the tubercles 
 had lost their virulence. The attempt was, therefore, an inoculation with dif- 
 ferent material. 
 
 My attempts, therefore, justify me in the conclusion that only the inoculation 
 with bacilli-bearing substances can cause genuine tuberculosis in the animals used 
 for experiment. A distinction in the effect of inoculation from material coming 
 from tuberculous processes of various kinds, (such as miliary tuberculosis, phthisis, 
 scrofula, fungous diseases of the joints, lupus, perlsucht, and other forms of animal 
 tuberculosis) I have not been able to discover. But also in tliis regard the various 
 sorts of tuberculosis show a perfectly uniform behavior 
 
 F.— EXPERIMENTS IN INFECTION WITH REINCULTUREN OF TU- 
 BERCULOUS BACILLI. 
 
 This second group of infection experiments forms the conclusion of the proof 
 that tuberculosis is an infectious disease and that it is conditioned upon tuberculous 
 bacilli. Up to this time it has been proved that tuberculous bacilli occur in all 
 tuberculous disease processes and exclusively in these. Further, that only tuber- 
 culous bacilli-bearing substances have the power of causing tuberculosis. But 
 since in both cases the bacilli were still united with parts of the body, the suppo- 
 sition was justified that besides the bacilli still another material of importance, 
 perhaps even the real infectious material, might be present while the bacilli played 
 
Y2 JETIOLOGY OF TUBERCULOSIS. 
 
 only a secondary part. This question could only be decided by inoculating the 
 bacilli perfectly pure and separate from all parts of the body. If they then also 
 created tuberculosis, they must be the only and indisputable infectious material of 
 tuberculosis. The high importance which belong to just this part of the investi- 
 gation demanded that the strictest prudential measures should be taken to exclude 
 all errors. With regard to this, as in the former attempts, for every single exper- 
 iment several freshly bought animals were used. Besides this special counter- 
 acting attempts went along with most of the attempts. The animals of every 
 experiment were in a special cage and were strictly separated from all other tuber- 
 culous ones ; they were also killed as early as possible to prevent a collision with 
 spontaneous tuberculosis and any objection arising therefrom. Further, as various 
 methods of infection as possible and as various species of animals were used in 
 order to find out the working of the reinculturen in this direction. The greatest 
 care was used in the disinfection of all the vessels and instruments used, especially 
 the syringes. The culturen serving for infection consisted (as was specially 
 proved almost every time), wholly of tuberculous bacilli. The same were lifted 
 with all caution by means of platinum wires heated until red from the stiffened 
 blood serum, which, as has already been expressly mentioned, can easily be done 
 without tearing ofE the least bit of the blood serum. It is therefore not too much 
 to claim that in most of the attempts absolutely pure bacilli masses were used to 
 which nothing of the breeding ground on which they grew clung. Moreover, in 
 several attempts sterilized blood serum was injected into the animals, which 
 served for the counteracting attempts without the appearance of a trace of tuber- 
 culosis. One can therefore claim with all certainty that when genuine tuberculosis 
 is caused by the infection with a tuberculous bacilli-reincultur, which has been 
 continued through several successive breedings, this is to be ascribed alone to the 
 effect of the tuberculous bacilli. 
 
 First experiment : Reincultur of miliary tubercles of the human lung (No. 
 33 in the former enumeration of the reinculturen) cultivated through five suc- 
 cessive breedings for fifty-four days, subcutaneously inoculated into four guinea 
 pigs. Two animals in the same cage were not inoculated. In the inoculated 
 animals after forteen days the inguinal glands swelled, the places of inoculation 
 changed into abscesses and the animals began to grow emaciated. One of them 
 died after thirty-two days, the others were killed on the thirty-fifth day. The 
 inoculated guinea pigs, as well the one which died as the three which were killed, 
 showed tuberculosis of the spleen, liver and lungs to a high degree ; the inguinal 
 glands were greatly swollen and caseous, and, moreover, decidedly more so on 
 the inoculated side ; the bronchial glands were little swelled. The two uninocu- 
 lated animals showed no trace of tuberculosis. 
 
 Second experiment : Reincultur from the tuberculous lung of a monkey, 
 (No. 11) cultivated ninety-five days in eight successive breedings, inoculated sub- 
 cutaneously into six guinea pigs. Two animals for counter-experiment remained 
 uninoculated. All the animals were killed after thirty-two days and the six in- 
 oculated were found tuberculous to a high degree, the two others healthy. 
 
 Third experiment : Reincultur from a perlsucht lung (No. 37) cultivated for 
 seventy-two days through six successive breedings, subcutaneously inoculated 
 in'o five guinea pigs ; one animal remained uninoculated. "When the animals 
 
jKtioi,ogt of tobeecdlosis. 'is 
 
 ■were killed after thirty-four days the inoculated showed themselves tuberculous, 
 the uninoculated healthy. 
 
 Fourth experiment : Reincultur from the tuberculous lung of amonkey (No. 
 11), cultivated 113 days in nine successive breedings, subcutaneously inoculated 
 into two guinea pigs, one German marmot, six white rats, five white mice, four 
 field mice, two hedge hogs, six domestic fowls, four doves, two sparrows, three 
 eels, one goldfish, five frogs, one turtle. Of these animals only the guinea pigs, 
 the marmot and the field mice became noticeably sipk. These were killed fifty- 
 three days after the inoculation and all found tuberculous to a high degree. The 
 tuberculosis of the marmot has, according to all appearance, a very great resemb- 
 lance to that of the guinea pig. The spleen is very much enlarged and hasagrey- 
 ish-red marbled appearance, also the liver appears permeated by large yellowish 
 herds. The tuberculously changed organs of the field mouse also look very charac- 
 teristic. The inguinal glands are considerably enlarged and caseous, the lungs 
 permeated by numerous grey knots from the size of a poppy-seed to the head of 
 a pin, and liver and spleen permeated very uniformly with many whitish tubercles 
 as large as a grain of millet, so that these latter gained a very dainty sprinkled 
 appearance. All the other animals of this experiment were killed two months 
 later and it appeared in their investigation, that one of the five white mice had 
 some grey knots in the lungs, the others were healthy, as were also the rats and 
 the hedge hog. Of the domestic fowls, three had the large tuberculous knots in 
 the intestines and in the liver characteristic of this species of animals. The rest 
 of the animals were healthy. 
 
 Fifth experiment : Reincultur from the closed vomica of a phthisic lung (No. 
 26), cultivated for twelve months in sixteen successive breedings and subcutan- 
 eously inoculated into seventeen guinea pigs, two other animals remaining un- 
 inoculated. With these animals observations were made as to the effect of 
 means which have the power of hindering the development of the tuberculous 
 bacilli and they could therefore not be killed. In spite of the fact that partly 
 arsenic, partly carbolic acid had been used to the greatest possible extent, tlie tu- 
 berculosis ran its course just the same as in the former animals, the lymph-glands 
 swelled considerably, emaciation occurred, all the animals died in the fourth to 
 the sixth week and were tuberculous in a high degree. The two uninoculated 
 animals were then killed and found healthy. 
 
 Sixth experiment : The following reinculturen, first, from lupus (No. 35) in 
 eight successive breedings continued for five months ; second, from a fungous 
 joini (No. 34) in seven successive breedings for four months; third, from a scrof- 
 ulous gland (No. 39) in seven successive breedings for five months ; fourth, from 
 miliary tuberculosis, (No. 32) in twelve successive breedings for nine months ; 
 fifth, from the vomica of a phthisic lung (No. 35) in nine successive breedings for 
 six months ; sixth, from a perlsucht knot (No. 39) in eleven successive breedings 
 for nine months — were subcutaneously inoculated, and, moreover, from every one 
 of the culturen four animals were inoculated. The mice were put in twos into 
 roomy glasses. Some animals died after a few days, apparently in consequence 
 of the influence of the Imprisonment. All the others visibly grew ill, the inguinal 
 glands began to swell, the animals became emaciated and suffered from difficulty 
 of breathing. In the course of four to six weeks they all died. The examination 
 
74 ETIOLOGY OF TTIBF.ECULOSIS 
 
 of some of these animals was utterly prevented or only incompletely possible, 
 because the still living fleld-mice, in spite of having abundant vegetable food, often 
 gnawed their dead comrades and ate up the inner organs of the same with great 
 ravenousness. Nevertheless, from each single division of this experiment some 
 animals remained for examination, and it could therefore be determined that they 
 all perished from a high degree of tuberculosis of the lungs, liver and spleen. A 
 distinction in the conduct of the tuberculosis proceeding from the various rein- 
 culturen was not to be recognized. The general appearance of the pathological 
 changes was identical in all animals and so was the appearance of the single lit- 
 tle knots to the naked eye, as well as their microscopic conduct and especially 
 their tuberculous bacilli contents. For this experiment it is worthy of notice 
 that the animals had been in imprisonment only a few days when they were in- 
 oculated, and that a large number of other fleld-mice imder the same conditions 
 had been kept in glasses for months without a single one of them becoming tuber- 
 culous. 
 
 Seventh experiment : Since fleld-mice are such a sure and convenient re- 
 agent for tuberculosis, for the purpose of experiments which I made with Dr. 
 GafFky twenty-four fleld-mice were subcutaneously inoculated with the reincul- 
 tur from a phthisic lung (No. 1) cultivated for seven months in twelve successive 
 breedings. These experiments were made in regard to the influence upon tuber- 
 culous animals of substances hindering the development. Also from these ani- 
 mals, which were treated with inhalations of easily evaporating substances, some 
 died after a few days of pneumonia, tuberculosis developed itself in all the 
 other, and ran its course in the same way as in the mice of the previou ! experi- 
 ment. Under dissection, a well-marked tuberculosis of the lungs, spleen and 
 liver always showed itself. 
 
 Eighth experiment : For the same purpose five guinea pigs were inoculated 
 with reincultur from caseous pneumonia (No. 28) cultivated for six months in 
 eight successive breedings ; further, four guinea pigs with reincultur from a 
 phthisic lung (No. 24; cultivated for six months in ten successive breedings, and 
 six guinea pigs with reincultur from tuberculosis of the testicles (No. 33) culti- 
 vated for three months in five successive breedings — all subcutaneously. These 
 animals had also various gas-like development-hindering substances to breathe 
 in, but in spite of it became sick and emaciated, died within four to six weeks 
 and were under dissection all found tuberculous. 
 
 Ninth experiment: Reincultur of lupus (No. 35) cultivated for twelve 
 months in fifteen successive breedings subcutaneously inoculated into five guinea 
 pigs. This experiment was undertaken in order to see whether the continuation 
 of the cultur of tuberculous bacilli from lupus-skin for the space of a whole year 
 had any influence upon the virulence of the same. This was, neverthless, not 
 the case. The inoculated animals were taken sick just as surely and quickly as 
 in the former experiments ; two died in the fourth week, the others were then 
 killed and all found under dissection to be tuberculous in a high degree. 
 
 Tenth experiment: With the same intention the longest continued reincul- 
 tur (No. 1) of human lung phthisis, cultivated for eighteen months in twenty-six 
 successive breedings, was subcutaneously inoculated into four guinea pigs. The 
 course of the disease was just the same as in the ninth experiment. The animals 
 died in the fourth and fifth week of the inoculation and were tuberculous. 
 
ETIOLOGY OF TUBERCULOSIS. YS 
 
 Eleventh experiment : By former opportunities an essential difference in tlio 
 sensitiveness of house mice and field mice to inoculation -with tuberculosis had 
 shown itself. Again, therefore, twelve white mice were inoculated with areincul- 
 tur of miliary tuberculosis (No. 23), the same which harl served in the inocula- 
 tion of the fleld-mice in the sixth experiment, and, moreover, at the same time as 
 the field-mice. While the field-mice, as has already b^en said, became tubercu- 
 lous, the white mice remained for two months without any appearance whatever 
 of sickness ; they were then killed and tuberculous changes found in none of 
 them. 
 
 These eleven experiments have the one common feature, that the inoculating 
 substance was put into the animals subcutaneously. The effect was in general 
 the same as when fresh tuberculous pieces of tissue were inoculated subcutane- 
 ously. The little skin wound closed up and healed in the first days, then fol- 
 lowed gland swelling, emaciation, death, and dissection showed a great far-reach- 
 ing tuberculous erruption in lungs, spleen and liver, with the further characteris- 
 tic changes of these organs belonging thereto. Only in so far a distinction was 
 noticeable as that after inoculation of the reiuculturen the course of tuberculosis 
 was a more rapid one, than after the inoculation of tuberculous tissue. For 
 guinea pigs this difference in time can be reckoned on tlie average as about two 
 weeks. This appearance explains itself most naturally by the assumption that in 
 the inoculation of tuberculous tissue, the tuberculous bacilli are enclosed by the 
 latter and cannot, therefore, have their effect until the tissue is resorbcd, while 
 those in the reiuculturen can get immediately into the subcutaneous tissue of the 
 animal, and can immediately begin to act. The same is the case in the inoculation 
 of the auterior eye-chamber of rabbits, and the iris-tuberculosis arisiug from it, 
 and it is here the case to a more striking degree because the developement of the 
 tubercles can here be observed with the naked eye. Microscopically the tuber- 
 cles obtained by the inoculation of reinculturen resemble in every way those ob- 
 tained by the inoculation of genuine tuberculous tissue, and just the same the 
 tubercles arising spontaneously. They consisted of heaps of cells, which mostly 
 had tlie character of epithelioid cells and closed giant cells, and contained besides 
 thee, tuberculous bacilli in greater or less numbers. Their virulence could be 
 seen from the fact, that in all cases they had spread themselves out from the 
 subcutaneous tissue over all the organs favored by tuberculosis. Besides this, in 
 several cases, farther inoculations were carried cut upon other animals and tuber- 
 culosis regularly created thereby. The inoculation of the reinculturen remained 
 witliout effect only in some species of animals, little or not at all sensitive to tu- 
 berculosis. On the contrary it made the other numerous animals tuberculous 
 without exception, and as, besides this, all the animals used for counter-experi- 
 ments remained healthy, there could be no doubt that the question for the decis- 
 ion of which these experiments were undertaken, must be answered in the affir- 
 mative, and that the tuberculous baciili are to be considered the sole cause of 
 tuberculosis. 
 
 Nevertheless, it seemed necessary not to stop here, but also to introduce the 
 reinculturen of tuberculous bacilli into animals by all the other methods of infec- 
 tion used up to this time in investigations regarding tuberculosis, in order so to 
 prove in every direction their identity with the tuberculous virus. The methods 
 
76 JSTIOLOttY OP TUBEECHLOSIS. 
 
 used up to this time were the following : Inoculation into the anterior eye-cham- 
 ber of rabbits, injection into the abdominal cavity, injection into one of the 
 larger veins, inhalation of reincultur of tuberculous bacilli. 
 
 Inoculation of Reinoultueen in the Anteeiok Etb-Chambbk. 
 
 A cut several millimeters long was made in the cornea, and, moreover, on 
 the upper border of the same, and by means of a blunt hook as small a crumb as 
 possible of a reincultur was pushed through this into the anterior eye-chamber 
 of a rabbit. Some practice and patience are required for this, and on this ac- 
 count I afterward followed another method. The cultur, rubbed to pieces in dis- 
 tilled water, was taken into a syringe, whose needle must be very fine and sharp. 
 The point can easily be pricked through the cornea into the anterior chamber, 
 and the liquid can then be injected into it. This last method is so far more fav- 
 orable as that the quantity of the infectious material can be very easily con- 
 trolled. One sees plainly, in moving the piston of the syringe, how the cloudy 
 injecting fluid mingles with the aqueous humor in the eye chamber, and one can 
 inject much or little liquid as he will. A minimum of bacilli can be brought into 
 the anterior chamber, if the needle of the filled syringe be put into it, and with- 
 out a real Injection be taken out again, since traces of the liquid in the needle 
 mix with the water of the chamber, even if the piston of the syringe be not set in 
 motion. 
 
 Twelfth experiment : Little crumbs of a reincultur from a caseous- pneumonic 
 lung (No. 27) cultivated for three months in five successive breedings, were put 
 into the anterior eye-chamber of three rabbits. After a few days an intense iritis 
 developed, the cornea soon became cloudy and yellowish gray. The animals then 
 became emaciated very rapidly. They were killed after twenty-five days, and 
 beside the caseous-purulent destruction of the bulbua, swelling and caseous de- 
 generation of the lymph-glands of the lower jaw and of the base of the ear, very 
 numerous tuberculous knots, partly with whitish centres, were found in the lungs. 
 
 Thirteenth experiment: Reincultur from a perlsucht lung (No. 19) culti- 
 vated for three months in five successive breedings, was rubbed with sterilized 
 blood serum, and injected into the anterior eye-chamber of two rabbits. A third 
 rabbit received just such an injection of pure blood serum. In the case of the 
 first rabbits the same appearances as in the twelfth experiment occurred. Iritis 
 quickly running its course, and cloudiness of the cornea in a few days. The 
 eyes of the third rabbit showed no change. The animals were killed after 
 twenty-eight days. The rabbit into whose eye the pure blood serum had been 
 injected showed itself perfectly healthy ; the other two had caseous bulbi, swollen 
 lymph-glands provided with caseous spots on the lower jaw and beside the base 
 of the ear, and numberless tuberculous knots in the lungs. 
 
 Fourteenth experiment : Pour rabbits concerned. Pure blood serum was 
 injected into the anterior eye-chamber of the first. The needle of the syringe, 
 which contained blood serum with an addition of reincultur (from tuberculosis of 
 monkey No. 12, cultivated four and one-half months in eight successive breedings) 
 was put into the anterior eye-chamber of the second, but the piston was not moved ; 
 several drops of blood serum mixed with reincultur were injected into the anterior 
 eye-chamber of the third and fourth rabbits. In the case of these last two animals 
 
y^ITIOLOGY OF TUBERCULOSIS. YY' 
 
 there developed iritis suppuration of the bulbus, followed by rapid emaciation, 
 lu the case of the second rabbit, on the contrary, the eye remained unchanged in 
 the beginning and not until the second week did there appear single white yellow- 
 ish knots on the iris in the neighborhood of the point of injection, and proceeding 
 from this a typical iris tuberculosis developed itself. New little knots constantly 
 appeared on the iris, the iris laid itself into ray-shaped folds, but the cornea gradu- 
 ally became cloudy and thereby hid the other changes from view. The animals 
 were killed after thirty days. The first was perfectly healthy; in the second, 
 aside from the already mentioned changes in the eye, the lymph-glands on the jaw 
 were found swollen and permeated with yellow-white herds, the lungs and other 
 organs were still free from tuberculosis. The two last rabbits had again number- 
 less tubercles in the lungs. 
 
 Fifteenth experiment : Reincultur of miliary tubercles from a human lung 
 (No. 4) cultivated for four and one-half months in eight successive breedings, was 
 rubbed up with blood serum and the needle of a syringe filled with it and pricked 
 into the anterior eye chamber of six rabbits without, however, making an in j action. 
 In all the animals iris tuberculosis developed, in some of them a slowly spreading 
 infiltration of the conjunctiva with tuberculous knots, reaching beyond the neigh- 
 borhood of the point of inoculation. Two of the animals of this experiment killed 
 after four weeks had already caseously infiltrated lymph-glands on the neck, but 
 still no tubercles in the lungs. The other rabbits were killed after eight weeks 
 and more or less numerous tubercles were then also found in the lungs. 
 
 At various times rabbits received injections of reinculturen in the anterior eye 
 chamber.in order to test the influence of substances, which hinder the development 
 of tuberculous bacilli in these animals. Of these attempts which, as has already 
 been mentioned, I carried on with Dr. Gaffky, a report will be given on a later 
 occasion. It may be said here in passing, that beside numerous other means, 
 arsenic, * helenin, sulphuric hydrogen, and moreover always in the largest possible 
 doses and for weeks at a time, were used upon the animals. We cannot state a 
 favorable effect of one of these means in a single case. All the animals perished tu- 
 berculouslyjustas quickly as those which had not been treated with meanshiuder- 
 ing development. The infection took place in various ways ; partly by simple 
 inoculation (comp. experiments 7 and 8) partly by injection into the eye-chamber, 
 partly by injection into a vein. The rabbits infected from the eye-chamber concern 
 the following cases : 
 
 Sixteenth experiment : Reincultur of miliary tubercles of the human lung 
 (No. 22) cultivated for eight months in ten successive breedings, rubbed up with 
 distilled water and injected into the anterior eye chamber of two rabbits ; Rein- 
 cultur from a phthisic lung (No. 1) cultivated for thirteen months in twenty-one 
 successive breedings, injected in the same way into fifteen rabbits. Some of the 
 same reincultur one month later injected into six rabbits. All these rabbits perished 
 
 * The use of arsenic to fight tuberculosis has been often recommended in former timf s 
 and tried by many physloiaia. It was therefore natural to teat the influence of this on tu- 
 berculous animals. Our experiments occurred almost a year before the recommendation 
 of arsenic by Buohner appeared, and were, therefore, not induced by that. According to 
 Korab, helenin has prevented tuberculosis and sulphuric hydrogen was warmly recom- 
 mended bv Froschauer. 
 
T8 Z3TI0L0GY OF TDBERCULOSrS. 
 
 quickly with the already described symptoms and had always numerous tubercu- 
 lous knots in the lungs. 
 
 In all the cases of these experiments, in which very small quanlitifs of the 
 reincultur were successfully brought into the anterior eye-chamber, the c ffect was 
 exactly the same as after the inplantation of the natural tuberculous virus in the 
 anterior eye-chamber. Single tuberculous knots appeared in the iris, which in- 
 creased in number and led to caseous degeneration of the bulbus and flnaliy to 
 general tuberculosis. In so far, to be sure, a distinction existed in that the erup- 
 tion of little knots occurred earlier than after the inoculation with tuberculous 
 tissue. The probable ground of this appearance has already been discussed. A 
 very noteworthy fact has been gained from the experiments, namely, the consider- 
 able difference in the effect according as a small number of bacilli or a large 
 quantity of the same get into the eye-chamber. In the first case we see a process 
 slowly creeping on, in which the infectious material first spreads itself upon the 
 iris, then reaches the lymph-glands, makes these caseous and not until then forcing 
 itself into the course of the blood and so becoming sowed over other organs of the 
 body. If, on the contrary, a large number of bacilli are in the b' ginning deposited 
 in the anterior eye-chamber, then it has an appearance suggesting that the before- 
 mentioned way is unnecessary. Especially it appears as if the lymph-glands, 
 which usually offer an opposition to the progress of the bacilli and hold them 
 fast for a longer or shorter time, were passed over altogether. The appearance of 
 very numerous tuberculous knots in the lungs, spleen, etc., occurs as earlyin this 
 mode of infection as after the injection of tuberculous bacilli immediately into a 
 vein. Also the quantity of the little knots after the injection into the anterior eye- 
 chamber does not compare very unfavorably with the quantity of them after injec- 
 tion into the course of the blood. Now whether the explanation of this is to be 
 sought therein, that the bacilli of the anterior eye-chamber can really in any way 
 come direct into the course of the blood in quantities, or whether their great num- 
 ber, which suddenly overflows the lymph passages and glands lying before us, 
 causes most of the bacilli to break through the hindrance, so that only a few re- 
 main, that I must leave undecided. At all events this appearance is adapted to 
 give enlightenment as to the apparently inexplicable irregular conduct of tuber- 
 culosis with reference to the duration of its course and to the longer or shorter 
 local confinement. 
 
 Injection of Rkinoultubbn into the Abdominai. Cavity. 
 
 The reinculturen, rubbed up with blood serum or distilled water, were filled 
 into a disinfected syringe, the point of operation on the abdomen of the animal 
 wag disinfected with sublimate solution, and then the needle slowly driven through 
 the covering of the abdomen so that the intestines remained unhurt, and then the 
 liquid was squirted into the abdominal cavity. This of itself very simple opera- 
 tion can easily be performed upon animals whose intestines are not constantly 
 flllted with firm, unyielding matter, and I have always succeeded with guinea pigs, 
 rats, mice, cats, etc., without causing injury to the intestines or traumatic perito- 
 nitis. Rabbits are less adapted for this experiment on account af the closely filled 
 eoecum. In order to obtain as quick an effect as possible, considerable masses 
 of reincultur were always injected. The abdominal cavity, like the eye-chamber, 
 
- ETIOLOGY OF TDEEECUL08IS. 79 
 
 reacts diflferently according to the different quantities of tuberculous virus. After 
 an injection of pus containing few bacilli there arose on the peritoneum, as we have 
 already seen, a disseminated tuberculous eruption, then a development of little knots 
 in the omentum and the spleen. But when masses of tuberculous bacilli were 
 injected into the abdominal cavity of guinea pigs, then they were principally taken 
 up by the large omentum. This rolls itself together and forms a horizontally-ex- 
 tending, thick, sausage-like roll, which on intersection has the greatest resem- 
 blance to an intersected, greatly swollen, and freshly caseous lymph-gland. lu 
 these white-yellowish, quite compact herds of the omentum enormous quantities 
 of tuberculous bacilli are found, most of which are in a fine state of spore forma- 
 tion. Besides this, as microscopic investigation shows us, the swollen spleen, tho 
 liver and the peritoneum are abundantly supplied with tuberculous bacilli, but 
 the death of thgse animals occurs s) early that the development of knots visible to 
 the naked eye has not had time to occur. An effusion of liquid was not found in 
 the abdominal cavity of guinea pigs, but was found in dogs and cats. On the 
 contrary, in guinea pigs, such a large quantity of clear, faintly yellow liquid was 
 found in the pleura that the lungs were compressed by it, and this caused the death 
 of the animal. The guinea pigs usually died ten to twenty days after theinjection. 
 If a smaller quantity of cultur substance is squirted in, the course of the disease is 
 of longer duration and there is then a development of visible, extraordinarily 
 numerous tuberculous knots, particularly upon the peritoneum, on omentum, in 
 the spleen and liver. The species of animals less subject to tuberculosis — dogs, 
 rats, white mice — do not succumb even to the injection of abundant bacilli until 
 after some months. But they then show also an unusually abundant tuberculous 
 eruption in the abdominal organs, but, on the contrary, less numerous knots in the 
 lungs. 
 
 Seventeenth Experiment : Reincultur from the tuberculous lung of a monkey 
 (No. 11) cultivated for six months in eleven successive breedings, was rubbed up 
 with blood serum and injected into ten guinea pigs, a half cubic centimeter into 
 each. Two animals for counter experiment received, the one just such an injec- 
 tion of pure blood serum, the other, which had a fresh, large wound from a bite, 
 no injection at all. Of the animals which had received the injection, deaths 
 occurred after ten, thirteen, sixteen, seventeen, eighteen days. The others, as well 
 as the " controlthiere*" were killed on the twenty-fifth day. In the guinea pig 
 which died fijst the large omentum was rolled together, greatly thickened, and 
 infiltrated with a yellowish-white brittle substance ; no knots were visible on the 
 liver and spleen. The other animals of this experiment, as well those which died 
 as those which were killed, had, besides infiltration of the omentum, already tu- 
 berculous eruption of the spleen and liver. The controlthiere were perfectly 
 healthy. 
 
 Eighteenth Experiment : Reincultur of the tuberculous lung of a monkey 
 (No. 11) cultivated for five and one-half months in ten succi ssive breedings, 
 rubbed up with blood serum, was injected into the abdominal cavity of two full 
 grown vigorous cats. The one cat died after nineteen days. The omentum was 
 rolled together, very much thickened, and infiltrated with a whitish compact mass. 
 The serous covering of the intestines and the peritoneum had lost its lustre, the 
 
 * Animals for counter experiment. 
 
80 iETIOLOGY OF TUBBECULOSlS. 
 
 spleen was greatly enlarged. The infiltration of the omentum consisted, as 'n the 
 guinea pigs of the previous experiment, of thick masses of tuberculous bacilli, em- 
 bedded mostly in cells. With the naked eye no knots could be seen in the lungs, 
 spleen and liver, but microscopically these organs were permeated already by an 
 unusually abundant tuberculous eruption. The second cat was killed after forty- 
 three days, and there were already tuberculous knots as large as a millet seed in 
 great numbers, quite uniformly spread over the lungs, spleen and omentum, while 
 in the liver the number was comparatively small. Both cats were to havereceived 
 ii syringefull of the injecting liquid, therefore an equal quantity, but the second 
 was very uneasy during the operation and only a small part of the liquid could be 
 Luccessf ully injected ; on which account the tuberculosis had a considerably longer 
 course, and fewer tuberculous knots developed which had time to reach a consider- 
 able size. 
 
 Nineteenth Experiment: Reincultur of miliary tuberculosis (No. 22) culti- 
 vated for three months in five successive breedings, rubbed up with blood serum, 
 and two cubic centimeters of this liquid injected into the abdominal cavity of a 
 female dog several years old. A half cubic centimeter of the same liquid was 
 inject( d into a male dog some months old. In the first weeks after the injection 
 no change could be seen in the animals. After the third week the female dog 
 lost her briskness, she ate less, and a noticeable swelling of the body occurred. 
 This animal was killed at the beginning of the fifth week. In the abdominal 
 cavity was a quite abundant effusion of a clear, faintly yellowish liquid. The 
 omentum, mesenterium, ligaments of the womb and peritoneum were sprinkled 
 over with many tuberculous knots, as were also the surface of the intestines and 
 bladder. The enlarged spleen,the liver and lungs contained numerous miliary 
 tubercles provided with tuberculous bacilli. The places of injection could no 
 longer be recognized. The second dog appeared sick for a time, had also plainly 
 an effusion of liquid in the abdominal cavity, and became emaciated ; finally it 
 recovered and developed very vigorously. This dog, together with a female from 
 the same litter, received five monthsJater an injection from the same reincultur, 
 this time however of two cubic centimeters. The result was the same in both 
 animals: for some weeks they showed no symptoms of disease, then became 
 emaciated and were attacked by ascites. One animal died after five weeks, and 
 then the other,which was already very weak, was killed. The information gained 
 from the dissection was exactly the same as in the case of the first dog. Omen- 
 tum, peritoneum, spleen, liver and lungs were supplied with extraordinarily many 
 tuberculous knots. 
 
 Tliis experiment is in so far of special interest as that one dog after the in- 
 jection of a half cubic centimeter of bacilli liquid was, to be sure, taken sick, but 
 recovered. This is the only case of tuberculosis in animals which I have seen 
 recover. The hope has often been expressed that, as in the case of inflammation 
 of the spleen, a preventive inoculation with weakened virus might be used against 
 tuberculosis. But if one recovery from tuberculosis gives protection against a 
 second attack of the disease, for which, by the way, experience by the sick bed 
 gives no ground of hope, then this dog should have had immunity against further 
 experiments in infection. But this was not the case, and this circumstance sp 
 against the justification of such hopes. 
 
 Twentieth experiment : Of five cats the first received an injection of piue 
 
JETIOLOGY OF TUBERCULOSIS 81 
 
 blood serum, died ; second the same serum with aa addition of reincultur No. 33 
 (miliary tubercles of man, cultivated f(jr five months in eight successive breedings;) 
 the third from ruincultur No. 1 (lungphthisis of man, cultivated forseven months 
 in twelve successive breeds) ; the fourth from reincultur No. 16 (perlsucht knot, 
 cultivated for five and a half months in nine successive breedings) ; the fifth from 
 reincultur No. 13 (tuberculosis of monkey cultivated for three months in five 
 successive breedings). Just the same was done with five guinea pigs. Of the 
 last, one each died on the twelfth, fourteenth, fifteenth and twenty-first days. 
 The controlthier was killed on the twenty-second day. Of the cats the fourth 
 died on the twenty-second day, the third on the twenty-seventh day, the other 
 animals were killed on the twenty-eighth day. All the animals into which the 
 bacilli liquid had been injected showed the familiar tuberculous changes in a 
 state of development corresponding with the space of time since the injection. 
 As well the cat as the guinea pig into whose abdominal cavities pure blood serum 
 had been injected, were wholly free of tuberculosis. This experiment, like sev- 
 eral previous ones, was undertaken to test any possible differences which might 
 exist in the results of bacilli culturen originating in the various forms of tuber- 
 culosis. But this time also the expectation cherished was not fulfilled ; for the 
 tuberculosis generated by the various reinculturen conducted itself exactly the same 
 in all, in the cats as well as in the guinea pigs. 
 
 Twenty-first experiment : Reincultur from tuberculosis of monkey (No. 
 11, cultivated for five months in ten successive breedings) was injected into the 
 abdominal cavity of five rats. These animals were fed for some time beforehand 
 with the dead bodies of tuberculous guinea pigs. In the case of other rats which 
 belonged to the same feeding experiment and had been killed, only individual 
 grey knots had been found a few times. But when the rats, into whose abdom- 
 inal cavity tuberculous bacilli had been injected, were killed, after five weeks, 
 numberless tub^rculous knots were found in the lungs, in the greatly enlarged 
 spleen, and in the liver and omentum. 
 
 Twenty-second experiment : Reincultur (No. 24, from a phthisic lung, cul- 
 tivated for five months in nine successive breedings), rubbed up in distilled vpater, 
 was injected into the abdominal cavity of the following animals ; six guinea pigs, 
 three cats, four white mice, four domestic fowls, eight doves. The guinea pigs 
 died in from ten to seventeen days, the cats one each on the fifteenth, twenty- 
 third and twenty-fourth days. The results as found in the dissection were the 
 same as in the other experiments. The mice, fowls and doves, to be sure, re- 
 mained alive, but were rough, thin, and seemed sick. As they did not recover, 
 they were all killed at the end of ten weeks. The mice showed the same appear- 
 ance as the white rats ; they had quite numerous tuberculous knots in the lungs 
 and very many in the greatly enlarged spleen. In the fowls and doves were 
 found such knots as have already been described in the intestines and in the 
 liver. 
 
 Injection of REiNonLTUEBN in thb Veins. 
 
 By this method the infection of the animal is wrought most quickly and in 
 the manner most productive of result. The body is at once overfiowed by means 
 of the blood with as great a quantity of the infectious matter as one wishes. 
 Said matter has no need lo overcome the hindrances put in its way, by the lymph- 
 
82 JETIOLOGY OF TUBEECUL08IS. 
 
 glands, etc., as when other methods are used, but spreads itself immediatelyover 
 all the organs and causes a great and quite uniformly distributed tuberculous 
 eruption. The mode of infection has plainly the greatest resemblance to that of 
 miliary tuberculosis in man, where the tuberculous virus also makes its way into 
 the blood and so is carried everywhere, By the help of injection into the veins 
 tuberculous knots can be called forth in all the organs in such short time, and in 
 so enormous numbcis as is never the case in spontaneous tuberculosis ; a mistak- 
 ing of one for the other is therefore here completely excluded. The liquid in 
 which the reinculturen of tuberculous bacilli were divided as finely as possible 
 was filtered through fine gauze, in order to keep back all coarser particles, and 
 then injected with one of the formerly described disinfected syringes, into the 
 vena jugularis, or according to Aufrecht's example, direct into the ear-vein of a 
 rabbit which had been laid bare. 
 
 Twenty-third experiment : Of twelve rabbits, two had a half cubic centi- 
 meter of pure blood serum injected into the ear-vein ; four rabbits received in 
 the same manner blood serum with an addition of reincultur No. 11 (tuberculosis 
 of monkey, cultivated for six months in eleven successive breedings — compare the 
 seventeenth experiment) ; three rabbits blood serum with reincultur No. 1 (from 
 phthisic lung cultivated for six months in ten successive breedings) ; three rab- 
 bits, blood serum with reincultur No. 19 (perlsucht lung, cultivated four months 
 in seven successive breedings). In the first days after the operation nothing 
 striking was to be noticed in any of these rabbits. The two first remained brisk 
 and vigorous, all the others began to breathe hard in the second week, and became 
 emaciated with unusual rapidity. The first rabbit (injection with cultur No. 1) 
 died after eighteen days ; the second and third (injection with cultur No. 11) after 
 nineteen days; the fourth (cultur No. 19) after twenty-one days; the fifth (cul- 
 tur No. 1) after twenty-five days ; the sixth and seventh (cultur No. 11) after 
 twenty-six and twenty-seven days ; two other animals on the thirtieth and thirty- 
 first days. The last and the two controlthiere were killed on the thirty-eighth day 
 after the injection. In the conduct of the lungs and other organs of the animals 
 treated with the various culturen, as in former similar experiments, no distinction 
 could be observed. In all the animals numberless miliary tubercles were found 
 in the lungs. The liver and spleen of all these animals contained an extraordi- 
 nary number of tubercles. In those which died first the knots were smallest, but 
 also most numerous. It was plain that the great number of tubercles had caused 
 such an early death. In the animals dying later the number of knots was some- 
 what smaller, but their size, on the contrary, decidedly larger. The two control- 
 thiere were found on dissection without a deposit of tubercles in any organ. 
 
 Twenty-fourth experiment : Pure culture of lupus. No. 85 (cultivated for 
 five months in eight successive breedings), rubbed up with distilled water and in- 
 jected into the ear-veins of five rabbits. These died from the thirteenth to the 
 eighteenth day after the injection and in the dissection showed the same state of 
 things as in the rabbits of the former experiment. 
 
 Twenty-fifth experiment : Pure culture of monkey tuberculosis No. 11 (cul- 
 tivated for six months in twelve successive breedings), rubbed up with distilled 
 water, was injected into the vena jugularis of ten rabbits which were intended 
 for experiments in inhalation with means of hindering the development. They 
 
iETIOLOGY OF TDBEECULOSI8. 83 
 
 all died in the course of two to three weeks after the injection and had great 
 quantities of tubercles in lungs, liver and spleen. 
 
 The tuberculous knots generated by injection into the course of the blood, 
 like all the other infections brought about by pure cultures, were not to be distin- 
 guished from the tubercles arising spontaneously. They contained tuberculous 
 bacilli in greater or lesser numbers and were virulent, for, when inoculated into 
 other animals, as was frequently done, they caused tuberculosis in the same man- 
 ner as the inoculations with genuine, spontaneous tuberculosis. 
 
 Inhalation of Pure Cultukes of Ttjbeeoulous Bacilli. 
 
 In order to bring tuberculous substances into the lungs of animals to be ex- 
 perimented on, either from a tracheotomic wound an injection was made into ihe 
 bronchise, or the infectious mass suspended in a liquid was made into spray and 
 breathed in by the animals. The first method does not sufHciently correspond 
 with the natural mode of infection, and is complicated in a disturbing manner 
 by the wound necessary for the operation. On that account I have chosen the 
 second method, which to be sure, for evident reasons, is not without danger to 
 the experimenter, and hence demands especial precautions. 
 
 The experiment was carried out in the following way : a very roomy box 
 with an opening on one side for the mouth of the atomizing apparatus, was 
 placed in a garden at a sufficient distance from inhabited rooms. The atomizing 
 apparatus was put on the outside of the box and projected with its mouth into 
 the interior of the box. By means of a rubber and a suitably long lead pipe 
 which was put through the wooden framework of a closed window, the appara- 
 tus was connected with the rubber bellows, and could s j be set in motion from 
 the room without the necessity of the experimenter's venturing within reach of 
 the atomized liquid. 
 
 Twenty-sixlh experiment: Pure culture from a human phthisic lung (No. 1) 
 cultivated fifteen months in twenty-three successive breedings was rubbed up 
 with distilled water and the liquid so thinned that it appeari-d almost clear. 
 What visible crumbs were still present in the liquid were deposited after a short 
 rest, and the upper layers of the liquid, showing scarcely any cloudiness, were 
 poured off and used for inhalation. On three successive days, each time in the 
 course of half an hour 50 cctm. were atomized and inhaled by the following ani- 
 mals in the box : eight rabbits, ten guinea pigs, four rats, four mice. After the 
 inhalation the animals were kept in siparate cages, and well taken care of. In 
 some animals, in ten days difficulty of breathing showed itself ; then three rab- 
 bits and four guinea pigs died in from fourteen to twenty-flve days. All the 
 other animals were killed twenty-eight days after the last inhalation. All the 
 rabbits and guinea pigs had numerous tubercles in the lungs, varying in size ac- 
 cording to the length of time the animal had lived after the inhalation. In the 
 animals dying latest, in those killed there were already tubercles in the liver and 
 spleen. The tubercles in the lungs were in every respect exactly like those which 
 were obtained in guinea pigs and rabbits through inhalation of phthisic sputum 
 in experiments undertaken for other purposes. Especially the tuberculous knots 
 generated by inhalation of phthisic sputum and those generated by the inhalation 
 of pure cultures had that in common, that when they had reached a certain size 
 
84: ^TIOLOOY OF TLTBEECUL08IS. 
 
 their alveolar spreading could already be plainly recognized by the naked eye. 
 They did not appear sharply rounded off and circumscribed, but embraced 
 mostly the centre of a lobulus. As the single alveoli were filled with a caseous 
 mass and hence appeared as fine whitish little points, they had a dull fine-grained 
 appearance, and on their border the white-yellowish little points of the caseous 
 alveoli showed themselves very plainly against the dark, greyish-red circle. 
 The largest tuberculous knots embraced an entire lobulus and sometimes ran to- 
 gether into neighboring knots, in this manner forming larger, thickened, white- 
 yellowish places in the lung which repeated completely the appearance of cas- 
 eous pneumonia. The spontaneous tuberculosis occurring in rabbits and guinea 
 pigs also shows in Ihe structure of the primary tuberculous knots the conduct 
 just described, namely, the alveolar spreading of the tuberculous process. This 
 circumstance, therefore, confirms the view already expressed, that the spontane- 
 ous tuberculosis of these animals is almost exclusively an inhilation tuberculosis. 
 
 The rats and mice which were killed had very numerous little grey knots 
 to the size of a hemp seed in the lungs, many of which possessed a white- 
 yellowish centre, yet the caseous dea:eneration was by far not so advanced as 
 in the lungs of the guinea pigs and rabbits. In the spleen of the rats and 
 mice also, only single grey knots were found. These animals, as has already 
 been often made prominent, are far less sensitive to tuberculosis, the single 
 tubercles develop in them much more slowh', and the further spread of the 
 tuberculosis to other organs does not occur so easily. 
 
 Also microscopically the tubercles arising from inhalation of pure cul- 
 tures resemble completely the genuine tubercles in the arrangement of the 
 epithelioid cells, the giant cells, and the contents in tuberculous bacilli. In 
 order to prove the infectious properties of the same, twentj--two guinea pigs 
 were inoculated subcutaneously in the abdomen with tubercles from various 
 organs, as well from several guinea pigs as from rabbits and from the lung 
 of a rat and of a mouse. These without exception were very soon attacked by 
 swelling of the inguinal glands on the side of the inoculation, became ema- 
 ciated and died in course of five to eight weeks of tuberculosis. 
 
 If we look over all the experiments with pure cultures we reach the fol- 
 lowing results: 
 
 Those animals which belong to species easily susceptible to tuberculosis, 
 oamely, guinea pigs, rabbits, field-mice and cats, became tuberculous without 
 exception in consequence of the infection with tuberculous bacilli. The num- 
 ber of these animals amounts to two hundred and seventeen (ninety-four 
 guinea pigs, seventy rabbits, nine cats and fori y-f our field mico). A number 
 of animals for counter experiments, treated in like manner with indifferent 
 liquids, and kept under the same conditions, on the contrary, without excep- 
 tion, remained free from tuberculosis. Of the less susceptible animals, as a 
 result of a simple subcutaneous inoculation, only domestic fowls, and, more- 
 over, only half of those inoculated, became tuberculous. But even dogs, rats 
 and white mice, which are usually very slightly susceptible to tuberculosis, 
 could not withstand the infection with large quantities of purely cultivated 
 tuberculous bacilli, and also without exception, became tuberculous. 
 
 The various methods of infection used had the same effect with the pure 
 
ETIOLOGY OF TDBEKOULOSIS. 85 
 
 cultures as with the natural tuberculous substances, only the first had a some- 
 what quicker effect than the last. 
 
 The products of the infection also were exactly like those obtained with 
 the natural infectious material, as well in their microscopic structure as in 
 their contents of tuberculous bacilli and in their virulent properties. 
 
 By the most careful attention to all the prudential measures needful for 
 the avoidance of mistakes in experimenting with tuberculosis, errors are with 
 certainty excluded from these experiments. With reference to this it may 
 also be made prominent here that in the same manner as with tuberculous 
 bacilli, an extraordinary number of experiments with other disease-producing 
 and non-disease-producing bacteria were made. Thtse were also put into 
 the anterior eye-chamber of rabbits, or were injected into their veins, they 
 were subcutaneously inoculated into rabbits, guinea pigs, mice, etc., and in- 
 jected into the abdominal cavity. Other bacteria were also used for experi- 
 ments in inhalation according to the method already described. But tuber- 
 culosis was never generated in tliese animals by these means. 
 
 In these experiments made with pure cultures, also only the tuberculous 
 bacilli completely freed from all original products of the disease, can have 
 been the cause of the tuberculosis. The proof of the proposition that tuber- 
 culosis is an infectious disease conditioned upon tuberculous bacilli, is here- 
 with concludi-d. One could be sure to say, and it has been said, that the 
 tuberculous bacilli are one cause for the occurrence of tuberculosis, but that 
 besides these other things, for example other micro-parasites, can likewise 
 generate tuberculosis. This supposition is, nevertheless, erroneous, because 
 as we have seen, in all cases cf genuine tuberculosis, tuberculous bacilli oc- 
 cur, and the manner of their occurrence allows us tJ infer a causative con- 
 nection with the disease. If in spite of this one would claim that besides the 
 tuberculous bacilli slill another special tuberculous virus exist, that would 
 justify a claim that beside trichinae and itch-mites still another specific, until 
 now unknown agent must exist as infectious material. We can, therefore, 
 with right say that the tuberculous bacilli are not only one cause, but the 
 only cause of tuberculosis, and that without tuberculous bacilli there is no 
 tuberculosis. 
 
 Therewith, tuberculosis is joined to inflammation of the spleen in knowl- 
 edge of its fetiology. The tuberculous bacilli stand in just the same relation 
 to tuberculosis as the inflammation of the spleen bacilli to that disease. 
 
 G.— THE KELATIONS OF THE TUBERCULOUS BACILLI TO THE 
 ^ETIOLOGY OF TUBERCULOSIS. 
 The investigations communicat d in the preceding have already gained 
 us so much knowledge of the biologic properties of the tuberculous bacilli, 
 and their peculiar behavior in the body attacked by them, that by their help 
 the aetiology of tuberculosis in its outlines may be stated with certainty. In 
 time we shall certainly become more thoroughly acquainted with the proper- 
 ties of tuberculous bacilli, and find out much that is new about them, which 
 will extend our views of the aetiology of tuberculosis, and in many ways 
 amend them ; nevertheless, this conviction cannot prevent us from forming 
 
86 AETIOLOGY OF TUBKKCULOSIS 
 
 an opinion now as to the relations of tuberculous bacilli to the disease caused 
 by them. 
 
 If we start from the experimentally proved proposition that only tuber, 
 culous bacilli have the power of generating genuine tuberculosis, and if we 
 apply ourselves to following the way which the bacilli take in the infection, 
 the question of the origin of the bacilli first forces itself upon us. Do they 
 occur anj'where, and mdependent of the human or animal organism, in the 
 outer world, as for example must be concluded of the inflammation of the 
 spleen bacilli and the micrococci of erysipelas ? The answer to this question 
 is of the greatest importance, not only for the aetiology, but also much more 
 for the prophylaxis. For, granted the tuberculous bacilli live in the decay- 
 ing animal or vegitable materials everywhere to be found, that they can in- 
 crease and form spores, then it would hardly be possible to keep these para- 
 sites away from man. But fortunately it is otherwise. Experience has 
 taught that the tuberculous bacilli grow much more slowly than all other 
 bacteria ; further, that they only grow in blood serum and meat liquid, and, 
 which is the main point, they need temperatures of more than 30° C. in order 
 to thrive. Also, when all these conditiins were found united, but the tuber- 
 culous bacilli were not protected against the luxuriant growth of other 
 quickly growing bacteria, then, as one can often enough see in the cultures 
 corrupted by foreign bacteria, the bacilli would be crowded out and killed 
 by the rival bacteria. Now, indeed, the conditions of development favorable 
 for tuberculous bacilli, especially the warmth of 30° C. day and night for 
 weeks are found united nowhere except iu the animal organism, and there is, 
 therefore, no other supposition possible than that they are dependent for their 
 existence wholly upon the animal and human organisms. They are there- 
 fore, genuine parasites, which cannot exist without a body to support them. 
 They are not like the anthrax-bacilli, accidental parasites, which usually com- 
 plete their course of development in the outer world and only occasionally 
 make an invasion into the animal body. The«re exists also an essential differ- 
 ence between the anthrax-bacilli and the tuberculous bacilli, in that the first 
 only multiply in the animal body, but never form spores, and for the develop- 
 ment into the permanent form must get into the outer world again, while the 
 tuberculous bacilli complete their entire course of development in the body 
 and in no way need a life in the outer world in order to take the form necc s- 
 sary for the preservation of the species. 
 
 Another question is, whether from the wide-spread bacteria, which often 
 get into the body, under favorable conditions, by means of adaptation and 
 successive breedings, tuberculous bacilli might not arise, or on the other hand 
 the tuberculous bacilli either in the body or after they had left the same 
 might not change into harmless bacteria. It would then not need the inva- 
 sion of specific bacteria to develop tuberculosis, but all would depend on the 
 necessary preparatory conditions for changing harmless into harmful bac- 
 teria, which would be all the same as one usually calls tendency. The rep- 
 resentation of a cross-breeding of tuberculous bacilli corresponds exactly with 
 the now often held but widely exaggerated views of the cha-ngeable nature 
 of bacteria, and has already found supporters. More value than that of a 
 
ETIOLOGY 01' TUBEECULOSIS. 8T 
 
 purely hypothetical view it can, nevertheless, not claim, for no facts speak for 
 it, but many against it. A certainly proved example of a breeding of harm- 
 ful bacteria from harmless ones, as is well known, does not yet exist, and 
 there is, therefore, no ground for ascribing to tuberculous bacilli origination 
 of that sort from indifferent bacteria. There is so much the less reason for 
 this, since among the numberless experiments in animals with disease-pro- 
 ducing and non-disease-producing bacteria, it has never occurred that in the 
 so very favorable breeding ground of the bodies of rabbits and guinea pigs, 
 , tuberculous bacilli have developed from other bacteria. On the contrary, all 
 experiments undertaken with the necessary precautionary measures teach 
 that tuberculosis only arises when genuine, that is to say, complete tubercu- 
 lous bacilli are united with the animal body. 
 
 The relations are different in regard to an eventual weakening of the tu- 
 berculous bacilli, since the weakening of the anthrax -bacilli can be cited for 
 the possibility of such a proceeding. Although the possibility of such a 
 change in the virulence is not to be disputed, nevertheless it must be con- 
 sidered that the weakening of the anthrax-bacilli is completed under circum- 
 stances which can only be brought about artificially, but which do not come 
 into play in ordinary circumstances either in the body or out of it. More- 
 over, against such a supposition the fact speaks, that tuberculous bacilli do 
 not show the slightest change in their qualities, especially iu their virulence, 
 when successive breedings have been carried on in cultures, that is to say out 
 of the animal body, and on a dead breeding substratum almost two years. 
 Also in the experiments of Fischer and Schill, which are reported in another 
 part of this paper, when tuberculous bacilli had been exposed for six weeks 
 to the influence of decay, no weakening of the virulence occurred. All this 
 speaks wilh decision against the supposition of an easily occurring change in 
 the virulent properties of the tuberculous bacilli. It is, perhaps, inconceiv- 
 able that the bacilli did not at some time proceed from other bacteria. But 
 after they had once become genuine parasites, they appeared to have the 
 peculiarity common to other parasites of holding to their qualities with great 
 
 obstinacy. 
 
 The only source for the origin remains, therefore, the animal or human 
 organism, and opportunity is not lacking to these parasites, owing to the ex- 
 traordinary diffusion of tuberculosis, to reproduce themselves in this field in 
 enormous masses, to develop the permanent form, to get into the outer world, 
 and to attack other victims. 
 
 Among the various forms of tuberculosis there are, to be sure, only cer- 
 tain ones which admit an easy transference of the baciUi. But these are ex- 
 actly the most frequently occurring forms, namely, phthisis and the tubercu- 
 lous diseases of the domestic animals. The other sorts of tuberculosis play 
 almost no part in reference to infection, partly because they remain so hidden 
 that they can only exceptionally cause infection. 
 
 If we ask first in how far phthisis can cause a transference of tuberculous 
 bacilli from diseased to healthy people, it is quite evident that here all the 
 conditions for the spread of the infectious material are present in fullest 
 measure. One only needs to remind himself that on the average one-seventh 
 
88 ^TIOLOOY OF TUBERCULOSIS. 
 
 of all men die of phthisis, and Ihat most phthisic patients, at least for some 
 weeks, often for months, throw out great quantities of sputum in which enor- 
 mous quantities of spore bearing tuberculous bacilli are contained. Of these 
 numberless infectious germs, which are spread everywhere on the ground, on 
 articles of clothing, etc. , much the greater part perish again, without ever 
 finding opportunity to establish themselves anew in a living organism. If 
 one farther considers, that according to the experiments of Fischer and Schill 
 already mentioned, the tuberculous bacilli can retain their virulence in a de- 
 caying sputum for forty-three days, and in dry air sputum for one hundred 
 and eighty-six days, then with regard to the great number of tuberculous 
 bacilli produced by the phthisically diseased, and to the endurance of the 
 bacilli in a damp as well as dry condition, it is easy to see and explain the 
 enormous diffusion of the tuberculous virus. 
 
 As to the method in which tuberculous virus is transmitted from the dis- 
 eased to the healthy no doubt can obtain. In consequence of shocks from 
 coughing of the diseased person, little particles are rent from the tough spu- 
 tum, sent into the air and so dispersed like dust. Now numerous experi- 
 ments have taught that the inhalation of finely dispersed phthisic sputum 
 not only makes those sorts of animals sensitive to tuberculosis, but also those 
 capable of resistance tuberculous with absolute certainty. That man should 
 be an exception to this is not to be supposed. It may, therefore, be taken 
 for granted that when a healthy human being accidentally finds himself in 
 the immediate neighborhood of the phthisically diseased, and inhales parti- 
 cles of sputum sent forth into the air, he can be infected by them But in- 
 fection taking place in this manner will probably not occur very often, be- 
 cause the bits of sputum are usually not so small that they can long remain 
 suspended in the air. Par more adapted for infection is, on the contrary, the 
 dried sputum, which, owing to the careless way in which the sputum of con- 
 sumptives is treated, can plainly get into the air in considerable quantities. 
 Not only is the sputum spit directly upon the ground, there dried and trod- 
 den under foot and stirred up in the form of dust, but it often becomes dried 
 and made into dust from the bed clothes, articles of clothing and especia'ly 
 from handkerchiefs, which are soiled even by the most cleanly patients by 
 wiping the mouth after expectorating the dangerous infectious material. The 
 experiences which have been gained from the investigation of the air, with 
 reference to bacteria capable of development, have taught that the bacteria are 
 not suspended m the air in an isolated condition, but that they, with the liquils 
 in wliich they have grown, dry on the surface of objects and only get into the 
 air when the dried up mass breaks off in little bits, or when ths bearers of the 
 dry bacteria liquid themselves are so light that they can be carried away by 
 the lightest breath of air. Assuch easily moved bearers, little bits of dust act 
 best, which consist of fragments of plant fibres, animal hair, epidermis scales 
 and similar materials. On that account defilement from vegetable tissues and 
 animal hairs and bed clothes, clothing and handkerchiefs, when caused by 
 phthisic sputmn are most to be feared. From spittoons and from the floor 
 dried sputum can only be separated in larger particles, which are not easily 
 raised up into the air ; on the contrary, one can scarcely conceive a more f av- 
 
ETIOLOGY OF TDBEECULOBIB. 89 
 
 orable arrangement for the dispersion of the sputum particles than the rapid 
 drying on cloth, from which with every motion little threads separate them- 
 selves, which carry the infectious material into the air, remain suspended 
 comparatively long, and when they finally sink to the groxmd are whirled up 
 again by the lightest breath of air. The investigations of the air carried on 
 by Hesse are specially instructive on this subject. 
 
 As has already been mentioned, the virulence of the dried sputum can 
 be preserved for months ; under some circumstances perhaps longer. The 
 last qualities of the virulence depend probably upon its containing well de- 
 veloped spores capable of developing germs. In any case, even if the dried 
 sputum retains its virulence only a few weeks, a consumptive in the condi- 
 tion in which one generally finds these sick persons is very well adapted to 
 provide his immediate surroundings with abundant quantities of infectious 
 material, and, moreover, in the most favorable form for the causing of in- 
 fection. 
 
 When the tuberculous bacilli are inhaled in dust-form, then they can either 
 remain in the upper air passages or force themselves into the alveoli just as is the 
 case with other inhaled particles of dust. The depth to which they enter the respi- 
 ratory tract will depend essentially on the manner of breathing ; if breathed deep 
 and with open mouth, they will get in farthest. Breathing through the nose will, 
 on the contrary, guaranty a certain protection against the entrance of the bearers 
 of the infectious material, since a considerable quantity of dust of the air breathed 
 is retained by the mucous membrane of the nose. But whether the tuberculous 
 bacilli, when they reach the bronchii and alveoli, are able to take firm hold and 
 establish themselves will depend on many circumstances. Especial influence on 
 this will be exercised by the slow growth of the tuberculous bacilli. Other disease- 
 producing bacteria, for example the anthrax bacteria, appear in consequence of 
 their rapid growth to grow very soon to such an extent and to exercise so quickly 
 a harmful influence on the cells in their neighborhood, that the ciliated epithelium 
 of the mucous membrane of respiration is no longer able to master and dispose of 
 them ; they can on that account establish themselves in the upper sections of the 
 respiratory passages and call forth the pathological processes peculiar to them. 
 This is taught by the wool sorters' disease and especially the affection running its 
 course under the term of anthrax ( f the larynx. Quite difEerent are the relations 
 for tuberculous bacilli. These need as many days as the anthrax bacilli hours to 
 reach a development worth mentioning, and before they reach it are in ordinary 
 circumstances usually ejected by ciliary motion of the epithelium long before this. 
 Therefore specially favorable moments must come to make their establishment 
 possible. These are certainly brought about by many conditions. Nevertheless, 
 the most important and most frequent helps for the establishment of the infection 
 appear to be furnished by such diseases as, for example the measles, for a time rob 
 the mucous membrane of respiration of its protecting epithelium, or which furnish 
 stagnating secretions in which the tuberculous bacilli can establish themselves. 
 Also, and that correctly, attention has been called to the fact, that by adhesions 
 of the lungs and imperfect form of the thorax, which hinder a suflicient movement 
 of the lungs and which are especially adapted to cause circumscribed collections 
 of bronchial secretions, the arising of tuberculosis, that is the establishment of 
 
90 ETIOLOGY OF TUBERCULOSIS. 
 
 the tuberculous bacilli, is favored. If one makes clear to himself the necessity of 
 such favorable moments for the entrance of the tuberculous bacilli, then it can no 
 longer appear so striking that many persons, in spite of constant association vfith 
 consumptives, are not infected, while others are plainly infected at the first oppor- 
 tunity, and still others after they have been exposed to the infection for a long time 
 finally, nevertheless, fall a victim to the same. In the case of the first mentioned 
 nothing helped the tuberculous bacilli, which were doubtless often enough inhaled, 
 and they were therefore removed again from the respiratory passages ; the second 
 had from the beginning a defective spot in their respiratory organs, on which the 
 bacilli were able to fasten themselves, and it was only necessary that the infectious 
 germ should reach just this spot ; tho last mentioned not until later had such a 
 defect and lost by means of it to a certain extent their immunity from tuberculosis. 
 The difficulties which stand in the way of the establishment of the tuberculous 
 bacilli in the upper air passages are greater and this fact explains the rare cases 
 in which they primarily become diseased. 
 
 Since by far the greatest number of cases of tuberculosis begin in the lungs, it 
 is to be supposed that the infection in all these cases has takeu place in the 
 manner just suggested by the inhalation of phthisic sputum dried and made into 
 dust. On account of the immence production of the infectious material and on 
 account of the frequent contact in which it must come with other parts of the hu- 
 man body, it is nevertheless not improbable that the infection can take place 
 from other parts than the lungs. So I would say, that the primary attacks of 
 lymph glands lying on the surface arising from scratches, skin-eruptions, etc., into 
 which tuberculous bacilli have accidentally entered, have formed the entrance gate 
 for the infection, from whence the bacilli have been carried farther and have got 
 into the lymph glands, then when the original point of infection has been healed, 
 it appears as if the disease-process had developed primarily in the glands. A 
 number of cases in which in otherwise healthy human beings caseous lymph glands 
 containing tuberculous bacilli were cut out from the back of the neck, I could not 
 otherwise explain, than that they arose through infection from scratches on the skin 
 of the head. Since the excrement of consumptives not rarely contains tuberculous 
 bacilli, the same is true in regard to the danger of infection from this as from the 
 sputum, when there is opportunity for its drying and being scattered as dust. But 
 this does not occur probably very often ; all the same this possibility of spreading 
 the infectious material is to be kept in view. 
 
 The second principal source for the tuberculous bacilli, namely, tuberculosis of 
 the domestic animals, appears not to have anything like the importance of the 
 phthisic sputum. The animals, as is well known, produce nosputum, so that during 
 their life no tuberculous bacilli get from them into the outer world by means of 
 the respiratory passages. Also in the excrement of tuberculous animals tubercu- 
 lous bacilli appear to be only exceptionally present. On the contrary, it is a fact 
 that the milk of tuberculous animals can cause infection. With the exception of 
 this one way, therefore, the tuberculous virus can only have effect after the death 
 of the animal and can only cause infection by the eating of the meat. Aside from 
 the probably only rarely occurring cases of direct infeciion, which can follow 
 from coming in contact with tuberculous parts of the flesh of little wounds and 
 exoriations of the skin, the reception of the infectious material will result in this 
 
AETIOLOGY OP TUBEEOTTLOSIS. 91 
 
 case only by means of the organs of digestion, and in accordance with this the first 
 appearances of the disease must first show themselves here. But now primary tuber- 
 culosis of the intestines is not at all f reduent in proportion to primary lung-tubercu- 
 losis—indeed, a decidedly rare affection. From this it is to be concluded, that the 
 infection in question does not often occur from eating the flesh of tuberculous 
 animals. Probably it would occur frequently if the visibly diseased parts of the 
 flesh were not put aside, as is usually the case, and if, as is almost invariably the 
 case, the meat were not eaten cooked. Also especially it must be considered that 
 the tuberculosis eatable animals, especially the perlsucht of cattle, remains more or l 
 less localized, so that after all only the use of the tuberculously altered lungs, 
 glands, etc., would be dangerous. That, nevertheless, the infection from the in- 
 testinal canal is indeed possible, is proved by the frequent cases of secondary in- 
 testinal tuberculosis of consumptives, which must be attributed to the swallowing 
 of their own sputa. It is, to be sure, strange that, although it is to be supposed, 
 that every consumptive swallows more or less of the tuberculous bacilli-bearing 
 8( cretion from his lungs, nevertheless intestinal abscesses are not to be found in 
 all. I explain this in the following manner : In the first place, the intestines ap- 
 pear to offer a still more unfavorable point of attack for the slowly growing tuber- 
 culous bacilli than the lungs. But further, the feeding-attempts with anthrax 
 bacilli and their spores, have taught that anthrax bacilli, which contain no 
 spores, are destroyed in the stomach, while the spores of these bacilli are 
 able to pass through the stomach unharmed. On that account only spore- 
 bearing substances can cause infection from the intestinal canal. The tuberculous 
 bacilli will conduct themselves most probably in this regard, like the anthrax- 
 bacilli, and only in case they are provided with spores will cause tuberculosis of 
 the intestines, provided they do not go through the intestinal canal too quickly to 
 render their germinating and establishing themselves at any point of the mucous 
 membrane of the intestines possible. Just the same holds, of course, for the danger 
 of an infection from tuberculous meat, and this circumstance may explain the 
 relatively rare infection from the use of such meat. 
 
 The same conditions hold for infection from the milk of cows suffering from 
 perlsucht. Before all things, if infection is to take place it is necessary that the 
 milk contain tuberculous bacilli. But this appears only to be the case when the 
 milk-glands themselves are tuberculously diseased. But since pctrlsucht-knots do 
 not often occur in the udder, the milk of perlsucht cows will often possess no in- 
 fectious properties. This explains immediately the contradictions in the state- 
 ments of the various authors, who have made feeding attempts with milk from 
 cows suffering from perlsucht. The one set maintain that they have gained posi- 
 tive results, and their statements are of such a sort that it is impossible to doubt 
 the correctness of their observations. The others, on the contrary, could obtain 
 no infection in the animals experimented with. This result is also correct. The 
 positive results were then obtained from milk which accidentally contained tuber- 
 culous bacilli, the negative wi;h milk which was free from bacilli. 
 
 If infection from tuberculous domestic animals in general does not appear 
 to be frequent, it must by no means be under-rated. Perlsucht of cattle and the 
 caseous changes in the lymph-glands of pigs are of so frequent occurrence tliat 
 they deserve close attention. If, now, we follow the tuberculous bacilli which 
 
92 ETIOLOGY OF TUBEECULOSie. 
 
 have got into the lungs by inhalation, into the skin by wounds, into the intestinal 
 canal by swallowing, in their further conduct in the body, we see that they often 
 remain for a long time — sometimes even permanently — in the place of their first 
 establishment. From herds of epithelioid cells they form liitle knots which enclose 
 giant cells, and regularly from the centre out, fall victims to coagulation-necrosis. 
 The appearances which are conditioned upon the gradual growth of such a herd, 
 and the regressive changes which always keep step with-it, have been described 
 in detail in a former section. The first sign of the spreading of the tuberculous 
 process into the neighboring regions is the formation of similar knots in the neigh- 
 borhood of the primary herd. The way, also, in which the migration of the bacilli 
 from the first herd to the place where the secondary knots arise, is to be conceived, I 
 have also already suggested. The following appears to me to be the simplest 
 explanation of this proceeding. The tuberculous bacilli, since they possess no 
 motion of their own, can only be moved along by elements possessing the power 
 of motion, or by currents of liquid. But since the tuberculous knots have no 
 vasal and one cannot see how other liquids, which are in motion, can get into the 
 tuberculous herd and sweep away bacilli from them, nothing remains but the wan- 
 dering cells, which according to experience, act the same part in other disease- 
 producing bacteria, which those elements perform, that provide for the transport 
 of the bacilli. The cell, laden with a bacillus only goes on until, under the influ- 
 ence of the parasite, it loses its power of motion. On the spot where the cell 
 came to a stand-still, a new tuberculous knot must arise. In this manner groups 
 of tubercles form, which melt, perish and cause destruction in the well-known 
 manner. 
 
 With the supposition that the wandering cells may be the bearers of the 
 bacilli, we see in the most natural manner the connection with the farther ex- 
 cursions which the tuberculous bacilli make in the body in almost all cases. 
 When the wandering cell movcsin the tissue-passages and must rely on its own 
 power of motion, then the distance which it travels is only a short one and the 
 newly arising infectious herd must lie in the neighborhood of the point of de- 
 parture. But as soon as the wandering cells move in the lymph- vessels and 
 the lymph-stream comes to their help in their movement, then they travel 
 greater distances, as is seen not seldom in the tubercles spreading themselves 
 out in the course of the lymph-vessels. But very often then the tuberculous 
 bacilli are swept away still farther in the lymph-vessels andled into the nearest 
 lymph-glands, where in like manner as in the first place of infection they call 
 forth the formation of knots and caseous degeneration. The changes condi- 
 tioned upon this in the gland-tissue appear usually to hinder a further progress 
 of the bacilli by the way of lymph-passages. But by this no insurmountable 
 barrier is placed in the way of the progress of the bacilli. They can, under 
 special conditions, get into the stream of the blood. This happens when, as 
 Ponfick has shown, the tuberculosis attacks the thoracic duct, and reaches the 
 interior of the same ; the tuberculous bacilli are then led direct from the lymph- 
 stream into the blood-stream. 
 
 A second, and moreover the mostfrequent cause for the entrance of tuber- 
 culous bacilli into the blood, has been discovered by Weigert. This is the 
 formation of tuberculous knots in the walls of veins and the breaking through 
 of the perishing knots into the lumen of the vasa. 
 
iETIOLOG-Y OF TUBEECDLOSIS 93 
 
 A third possibility is suggested in the case described in the earlier pages 
 of this paper, in which the bacilli grew into the lumen of an artery. In all 
 these casts the bacilli were rapidly swept away by the blood-stream, scattered 
 into the most -various organs of the body and there established. If Very many 
 baclli at one lime got into the blood, then the conditions are exactly the same 
 as in the experiment with the rabbit into whose ear-veins considerable quan- 
 tities of tuberculous bacilli from a pure culture were injected. As well in the 
 artificial as in the natural experiment, and in the same manner, tuberculous 
 knots arise in great numbers, and moreover epecially in the lungs, spleen and 
 liver. Why these organs are so specially favored demands explanation. The 
 connection between the localized tuberculous processes and the acute miliary 
 tuberculosis which formerly appeared so enigmatical, and on that account has 
 been characterized by many as impossible, has been made clear with unques- 
 tionable certainty by the discoveries of Ponfick and Weigert. This example 
 of the manifold forms of a disease warns us forcibly against considering patho- 
 logical changes, an d especially infection s diseases only from an anatomical point 
 of view unlessforcedto do so, but first of all to consider the setiological relations 
 as authoritative. 
 
 A considerable number of tuberculous bacilli do not always force them- 
 selves at once into the blood-passages. It can also occur that onlj' compara- 
 tively a few bacilli are carried along by the blood-stream. Then there arise cor- 
 respondingly fewer tuberculous herds, but which reach greater dimensions 
 because in this case life is longer preserved, than when an immense eruption of 
 tuberculous knots cause rapid death. Also in this matter the infection taking 
 place in the natural way conducts itself just like that artificially generated. 
 Sometimes only a very few bacilli get into the blood and only individual tuber- 
 cles are formed, which then in course of time grow to considerable dimensions. 
 This proceeding, which can repeat itself with intervening pauses, has been char- 
 acterized by Weigert very fittingly as chronic miliary tuberculosis, in contrast to 
 the acute, which, owing to the immense production of tubercles is quickly 
 fatal. 
 
 To these last mentioned forms of miliary tuberculosis are joined those 
 processes where, in certain places of the body, which are not easily suceptible 
 to an invasion from without and apparently without a herd causing the infec- 
 tion, a tuberculosis confined to the spot is developed. This sort of process, among 
 which the fungous carious infections are to be reckoned, arise strictly localized. 
 One can scarcely explain their occurrence otherwise than that a single infec- 
 tious germ, therefore a single bacillus, was deposited by the blood on the spot 
 in question. But how is a single bacillus to get into the blood ? Could it after 
 being inhaled into the lungs get into the lung capillaries without previously 
 causing' in the lung itself a tuberculous herd ? Such a supposition has to me 
 little probability. The almost regular appearance of caseous or calcareous 
 bronchial glands in the diseased conditions mentioned rather makes the sup- 
 position probable, that the lymph-glands are not always an unconquerable 
 hindrance to the further progress of the bacilli, and that individual bacilli just 
 as they are carried along by the wandering cells and the lymph-stream, can 
 also by help of the wandering cells leave the lymph-glands in centripetal di- 
 
94 ETIOLOGY OF TUBEBCULOStS. 
 
 rection again and by the lymph-stream be carried into the blood. I do not 
 doubt that, as in almost every case of miliary tuberculosis, the point of depar- 
 ture for the infection can be shown, one can also succeed in all cases of local- 
 ized tuberculosis of the inner organs, as well as of the bones and joints, when 
 they are dissected to find some older tuberculous herd, mostly perhaps caseous 
 bronchial glands, from which single bacilli could get into the blood. It is very 
 probable also, that tuberculous bacillar meningitis of children in so far belongs 
 here, as that in the same, although lungs, liver and spleen are very often free 
 from tuberculosis, the bronchial glands are almost regularly found caseous, 
 whence we may conclude that these latter in this case too are to be considered 
 as the primary disease-herd. To be sure it is peculiar, that in this form of 
 tuberculiisis, in which plainly not single but numerous tuberculous bacilli are 
 deposited by the blood, the pia mater is so favored a place of deposit. 
 
 If, as has already been shown in former parts of this work, the various 
 forms of tuberculosis must be declared identical on account of the same quali- 
 ties of the bacilli occurriog in them and the cultures gained from these, as well 
 as on account of the identity of the inoculating products proceeding from them, 
 the progressive knowledge of their mode of originating gives new proofs of 
 this supposition. At first sight, however different the forms of lung-phthisis, 
 acute and chronic miliary tuberculosis, the affections of the glands and mucous 
 membrane under the general figure of scrofula, tuberculosis of the bones and 
 joints, of localized tuberculosis of single organs, as for example the kidneys 
 and the intestines, may appear, we shall see without difficulty that they belong 
 together when we look at their mode of formation. Only lupus offers in so far 
 a certain difiiculty in the identification with tuberculosis, as clinic observation 
 state a distinction that cannot be overlooked in the conduct of lupus and un- 
 deniably tuberculi lus affections of the skin and mucous membrane. Neverthe- 
 less the aetiological reasons for the unity of these two diseases are too weighty 
 to retire before this difference, which possibly may find its explanation in the 
 individual disposition. 
 
 The relation is similar between the tuberculosis of animals, above all of 
 perlsucht and tuberculosis in man. These also must on account of the identity 
 of the parasites on which they are conditioned, be held to be identical with 
 human tuberculosis in spile of the differences in the anatomical behavior and 
 in their clinical course. It has, to be sure, been stated, especially with refer- 
 ence to perlsucht, that the transmission of this disease to man has not yet been 
 certainly proved. On the other hand the following may be said -. On account 
 of the very slow development of the disease, the place and time of the infec- 
 tion and therewith the source of the same can no longer be confidentl}' stated, 
 when the first plain symptoms appear. On this account in the frequent inha- 
 lation-tuberculosis the mode of infection can be determim d in a scientific 
 manner only in c^)mparatively few cases. Still less will this be possible in the 
 much rarer cases of intestinal tuberculosis arising from the use of flesh or milk 
 of cattle suffering from perlsucht. because here the uncertainty is heightened 
 by the easily possible confusion with other much more frequent kinds of in- 
 fection. It is therefore very questionable whether ever a case of human tuber- 
 culosis can without criticism be attributed to the use of the meat or milk of 
 
JSTIOLOGY OF TDBBEGULOSIS. 95 
 
 tuberculous animals. But if one thinks, that to the most various sorts of ani- 
 mals (cats, rabbits, guinea pigs, field mice) by inoculation with masses of 
 perlsucht and the pure cultures gained from them, a disease can be generated 
 with the greatest regularity which anatomically is exactly like the disease 
 caused by inoculation with tuberculous masses, and which kills the animals 
 with the same certainty as the last, then it is not to be expected that man 
 should be an exception to tbis disease-poison. If in the course of further in- 
 vestigations again a difference between the perlsucht and the tuberculous bacilli 
 should show itself, which would compel us to consider the same as only mar 
 relations, we should even then have all cause to hold the perlsucht bacilli ag 
 suspicious in the highest degree. From the hygienic standpoint the same mea- 
 sures must be taken against it as against the infection through tuberculous 
 bacilli, so long as it is not proved that man can bring perlsucht bacilli in coi - 
 tact with skin-wounds without danger, that he can inhale the same or bring 
 their spores into his intestinal canal without becoming tuberculous. 
 
 The considerable variety in the course of the disease in various individuals 
 of the same species, and in their sensitiveness to the tuberculous virus, appears 
 to speak against a common classification of all the disease-forms conditioned 
 by tuberculous bacilli. These are nevertheless appearances which reappear 
 in more or less marked a manner. One helps himself in this case by supposing 
 a different disposition for the disease, as well as what concerns the attack of 
 the same and its m^ ire or less intense course, without tliat an explanation of the 
 same is given by this characterizing of the appearance. A number of such 
 differences in the form of tuberculosis is already simply explained by the dif- 
 ference of the point of infection. Then the quantity of (he infectious material 
 originally taking effect seems to be of essential importance. Single infectious 
 germs are held within bonds more easily and for a longer time by the organism 
 on account of their slower development, so that they remain localized ; while, 
 when many germs are imported at once, they support each other in their work 
 of destruction. A definite representation of that which is characterized as 
 individual disposition one can make for all conditions, in which according to 
 our previous supposition, certain favorable moments, such as are afforded by 
 defects in the epithelial covering of the respiratory mucous membrane, stag- 
 nating secretions, disturbances of respiration, etc., aid the establishment of the 
 tuberculous bacilli. 
 
 If then a large number of the appearances combined under the expression 
 disposition may be referred to simple and easily explainable relations, there 
 nevertheless remain some facts hard to explain, or not to be explained, which 
 compel us to allow the supposition of a disposition to exist for the present. 
 This is above all the striking difference of tuberculosis in its course in children 
 and in grown people ; further, the undeniable predisposition of many families 
 for tuberculosis. In the last case many cases of tuberculosis laid at the door 
 of this predisposition might much better be referred to the increased opportu- 
 nity of infection. One can also think of special predisp:)sing causes belonging 
 to the family character, such as inclination to catarrh of the respiratory organs, 
 defective structure of the thorax. Nevertheless there are many observations 
 relative to this point which do not admit of such explanations. Moreover, 
 
96 ETIOLOGY OF T0BEECULOSIS. 
 
 single cases of the disease liave already oflen tauglit that one and the same 
 person is not at every time an equally favorable subject for the development 
 of the parasites, for, as is well known, it occurs not rarely that tuberculous 
 herds which had reached no slight, extent, shrivel, make scars and heal. That 
 is as much as to say that the same body which, at the invasion of the tuberculous 
 bacilli g'lve a favorable breeding-ground for the same, so that they could increase 
 and spread, gradually loses these favorable properties, changes itself into abad 
 breeding-ground and so sets a boundary to the further growth of the bacilli. 
 There existed, therefore, in the same person at one time a disposition for tu^ 
 berculosis and at another time not. Wherein this distinction is founded, 
 whether in a change in the chemical composition of the juices of thr, tissue, 
 or in physical conditions, that must be taught by later investigations. So much 
 is certain, that such differences exist and there is certainly nothing against the 
 supposition that similar conditions, favorableor unfavorable to the tuberculous 
 bacilli, may exist in certain persons not only for a time, but also during the 
 entire life. 
 
 What still concerns the much discussed question of hereditary tuberculosis, 
 after what has just been said, I can express in a few words. No facts exist 
 which justify the supposition that intra-uterlne or extra-uterine tuberculous 
 bacilli can be present in the organism of a child, without bringing about visible 
 changes in a comparatively short time. But until now tuberculosis has been 
 very seldom found in the foetus or in the newly born child, and we may, there- 
 fore, conclude that the infectious material has effect only exceptionally during 
 the intra-uterine life. This supposition is confirmed by the fact that of my 
 experimental animals, especially guinea pigs, which not seldom were pregnant 
 before or after the tuberculous infection, none have borne young which were 
 tuberculous at birth. The young coming from mothers tuberculous to a high 
 degree were free from tuberculosis and remained healthy for months. In my 
 opinion hereditary tuberculosis finds its most natural explanation, it it be sup- 
 posed that not the infectious germ itself, but certain qualities favoring the 
 development of the germs coming into contact with the body at a later period, 
 therefore, that which we call disposition, be inherited. 
 
 The aetiology of tuberculosis, as it was here developed on the foundation 
 of our knowledge of the tuberculous bacillus in detail, scarcely offers anything 
 new. Cohnheim had represented tuberculosis as an infectious disease and de- 
 scribed its setiology correspondingly before the discovery of the tuberculous 
 bacillus. In this direction, therefore, my investigations have brought no essen- 
 tial progress to science, and yet it must be considered as a gain that upon the 
 very important question of the infectious nature of tuberculosis, which until 
 then had been disputed by most, now such proofs are furnished as to admit 
 of no reasonable objections. Not less important is it, that the tuberculous 
 bacilli give a sure test of what in the future shall be considered as belonging 
 to the territory of tuberculosis. The diagnosis of tuberculosis will in doubtful 
 cases be made dependent upon the proof of tuberculous bacilli. Practice has, as 
 is well known, made use of this aid to a great extent and moreover with com- 
 plete success, and has thereby furnished a rich material for proving the correct- 
 ness of my opinion of the importance of tuberculous bacilli. Already from 
 
MnOLOQY OF TUBBECUL08I8. 97 
 
 this an appreciable advantage lias resulted in the discovery of the tuberculous 
 bacillus. But it is to be hoped, that also in other respects something may be 
 gained by it, which can be made useful in fighting the disease. After the ex- 
 periments already undertaken no great outlook appears to exist in a therapeutic 
 direction, of finding successful means of influencing the parasites in the body 
 of the patient. I would lay so much more value upon the prophylactic mea- 
 sures. These must partly be directed to directly destroying the tuberculous 
 bacilli by suitable methods of disinfection, partly tiny must strive to preserve 
 the healthy from contact with the tuberculous bacilli in all those conditions 
 in which a reliable destruction of the parasites is not possible. 
 
 It appears to me not to be too early to proceed against tuberculosis with 
 prophylactic measures. But owing to the great spread of this disease, all steps 
 which are taken against the same will have to reckon with the social condition, 
 and, therefore, it must be carefully considered in what way and how far one 
 may go on this road without prejudicing the advantages gained, by unavoid- 
 able disturbances and other disadvantages. It would lead too far to go into 
 a detailed discussion of the prophylaxis in this place, and I reserve my views 
 in regard to it for another opportunity. 
 
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