117 CORNELL UNIVERSITY. THE Bostnefl ^. Srtomer ITibrarg THE GIFT OF RO SWELL p. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE. 1897 Cornell University Library R 117.K26 Medical research and human welfare; a rec 3 1924 000 265 482 The original of tliis book 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/cu31924000265482 The Colver Lectures in Brown University 1917 Medical Research and Human Welfare By William Williams Keen The Colver Lectures in Brown University 1917 Medical Research and Human Welfare By William Williams Keen 1-4 (grotim Unlberatt^. €§6 Ceflj« £ut\nxt8, 1917 MEDICAL RESEARCH AND HUMAN WELFARE A Eecord of Personal Experiences and Observations during a Professional Life of Fifty-Seven Years BT W. W. KEEN, M.D., LL.D. (Brown) Emeritus Professor of Surgery, J^erson Medical College, Philadelphia BOSTON AND NEW TORK HOUGHTON MIFFLIN COMPANY ^ie Wattgiie J^tt0 Cambiibge :Vo.5"au COFYRIOHT, 1917, BY BROWN UNIVBRSITT ALI, RIGHTS RESERVED Patlished November iqij r\-2.X3 THE Colver lectureship is provided by a fund of $10,000 presented to the University by Mr. and Mrs. Jesse L. Rosenberger of Chicago in memory of Mrs. Rosenberger's father, Charles K. Colver of the class of 1842. The following sentences from the letter accompanying the gift explain the purposes of the foun- dation: "It is desired that, so far as possible, for these lectures only subjects of particular importance and lecturers emi- nent in scholarship or of other marked qualifications shall be chosen. It is desired that the lectures shall be dis- tinctive and valuable contributions to human knowledge, known for their quaUty rather than their number. In- come, or portions of income, not used for lectures may be used for the publication of any of the lectures deemed desirable to be so published." Charles Kendrick Colver (1821-1896) was a graduate of Brown University of the class of 1842. The necrologist of the University wrote of him : " He was distinguished for his broad and accurate scholarship, his unswerving per- sonal integrity, championship of truth and obedience to God in his daily life. He was severely simple and unworldly in character." The lectures abeady published in this series are: — 1916 The American Conception of Liberty and Government, by Frank Johnson Goodnow, LL.D., President of Johns Hopkins University. In boards, 63 pages; price, 50 cents. CONTENTS Pbefatobt 1 Human Welpabe 2 A New Ttpe of Subgeon 12 Anesthesia 15 Instbuments of Pbeosion 18 Bactebiologt 28 Pasteub's and Listeb's Achievements — Spon- taneous Genebation 29 Pasteub's Life and Work 33 The SiiiKwoBM 36 Anthbax 37 PUEBPEBAIi FeVEB 43 Chicken Cholera 45 Swine Plague 46 Htdbophobia 47 Antiseptic and Aseptic Subgery .... 63 Modebn Subgebt 54 Syphilis 60 Smallpox 64 Cholera 67 Bubonic Plague 69 vii CONTENTS Yellow Feveib 71 Malaeia 74 hookwokm 80 tubercdlosis 84 Canceb 88 Diphtheria 92 Cerebeo-spinal Meotngitis 100 Typhoid Fevek 102 Typhus 110 Malta Fever 113 Tetanus 115 Lepbosy , 120 Internal Secbetions and the Ductless Glands 122 Medical Research in Diseases of Animals . 136 Texas or Tick Fever 141 Hog Cholera 145 Research in Diseases of Plants .... 147 Bacteria in Soil 148 Cancer in Plants 153 Bacteria in Rocks 154 Conclusion 158 ILLUSTRATIONS W. W. Keen, 1861 and 1917 .... Frontispiece Plate I 38 Fig. 1, Anthrax Bacilli; Fig. 2, Hookworm; Fig. 3, Tubercle Bacilli. Fig. 4, Diphtheria Bacilli; Fig. 6, Typhoid Bacilli; Fig. 6, Tetanus Bacilli. Fig3. 1, S, 4, S, and 6 reproduced by the courteay of W. B. Saunders Company from Dr. A. C. Abbott's Hygiene qf TrarumU- tible Diaeasei. Chaet I 76 Monthly Distribution of Calls for Malaria at Cros- sett. Ark., 1915 and 1916. Reproduced by the courtesy of Mr. Wickliffe Rose of the Rocke- feller International Health Commission. Chart n 97 Mortality from Diphtheria in Fifteen American Cities before and after Antitoxin Treatment. By the courtesy of the Prudential Insurance Company. Chart m 99 Mortality from Diphtheria in Twenty Countries of the World before and after Antitoxin Treat- ment. By the courtesy of the Prudential Insurance Company. ix ILLUSTRATIONS PlATE n 104 Fig. 1, Different Phases of Development of the Malaria Parasite (Plasmodium). After Thayer and Hevetson. From Dr. A. C. Abbott's Hygiene 0} TranamiasibU Diemtea. Rg. 2, Typhoid Fly Tracks. By the courtesy o{ Fro{. W. M. L. Coplin, JeSerson Medical CoUege. Plate III , . . 152 Fig. 1, Nitrogen-fixing Nodules of the Garden Pea. ' From "Nitrogen-gathering Plants." by Karl F. Kellerman in Yearbook of the Department qf Agriculture for 1910. Fig. 2, Nitrogen-fixing Nodules of Alder. From "Nitrogen-gathering Plants," by Kellerman. Fig. 3, Fossil Bacteria from Montana. By the courtesy of Prof, Charles D. Walcott. MEDICAL RESEARCH AND HUMAN WELFARE MEDICAL RESEARCH AND HUMAN WELFARE A Record of Personal Experiences and Obser* vations During a Professional Life of Fifty-seven Years IN 1855, a young fellow of eighteen, without even a single acquaintance in Providence, I came to Brown, drawn by that intellectual magnet — Francis Wayland. At the Com- mencement Dinner I heard an old fellow of the class of 1805 respond for his class of half a century before. I looked at him askance and said to myself, "You old rascal, you ought to have been underground long ago and have left the earth to us young chaps!" But a long procession of the years has shamed me of my hasty judgment, for next June I shall cele- brate my fifty-eighth academic birthday! I humbly ask of him a posthumous pardon. How little I even dreamed that the most gilded future would bring me any such honor as falls to my lot to-day to address the Uni- versity. This has done more than evoke my 1 MEDICAL RESEARCH AND HUMAN WELFARE gratitude. It has caused me to review these more than six decennia. It has made me ap- preciate more than ever the extraordinary age through which I have lived, and the wonder- ful help that my Brunonian education has ever been to me in aiding humanity in some small measiu^e towards health and happiness. These reflections led me natxu-aUy to choose as my subject — "Medical Research and Hu- man Welfare : A Record of Personal Experiences and Observations during a Professional Life of Fifty-seven Years." HUMAN WELFABE What are the factors that promote Human Welfare? First, and by far the most important, is Good Health. Without that, one is crippled. Having it, one can achieve the rest, such as food, clothing, shelter, the other prime needs of the body, and for the mind, education, men- tal development, travel, books, pictures, and all the varied factors which collectively we call " CiviUzation." To them are to be added as far as possible the negative assets of life, such as freedom from sorrow and grief caused by HUMAN WELFARE death, especially the premature death of those dear to us. To aid us in achieving those blessings and free us from those sorrows Medical Research is our best friend. The human mind — especially the medical mind — is never content with things as they are. We are ever seeking to decrease our ignorance and increase our knowledge; to make things better, to devise new means for health and happiness. When the first man asked, "Why am I sick? " "How did I become sick? " "By what means can I get well?" Medical Research was born. For twenty-five centuries these questions as to health have been constantly and insistently asked and the medical profession has been try- ing to answer them. For many centuries we had only clinical ob- servation; that is, pain and the physical sur- face phenomena of the body of the patient — fever, eruption, swelling, wounds, fractures, and other accidents. Then in the sixteenth century the experimental method began slowly to arise. By the first method we had to observe for years and in many pai;ients. Nature's vagaries in different diseases and her different phe- MEDICAL RESEABCH AND HUMAN WELFARE nomena even in the same disease, after her haphazard method. By the second method, in a short time the same observer, having the now known causes of human and animals' disease at his beck and call, induces ia animals certain diseases under conditions chosen at wiU, varies these conditions one at a time, notes the differing results of each change, not only by his five senses, formerly his only allies, but by many instruments of precision wholly unknown fifty years ago and many of which even now cannot possibly be used on man. He can also verify his inferences not only by observing external phenomena, but by post-mortem examinations in animals of every internal organ at varying periods in the progress of the disease and so learn the "natural history" of the disease, the phenomena of its various stages, and the relative values of various remedies or opera- tions. This method is not only valuable in acute and fatal diseases, but may be even more so ia pro- tracted diseases when death from the original disease only reveals to us the end results, and not the early changes and later stages of the malady; while in non-fatal diseases, death 4 HUMAN WELFARE gives us the results of the intercurrent fatal malady which obscure those of the original disease. It is too often overlooked that for century after century Nature has been pitilessly per- forming her crude and cruel experiments and killing millions of human beings every year. She has inflicted untold suffering without any merciful anesthetic and with only occasional inadequate and passing relief by our narcotics. In place of these milUons of human beings an infinitesimally smaller number of animals have suffered far less and far less acutely in research and have yielded extraordinary and most beneficent results as I shall show. For seventy years past anesthetics, in prac- tically all save a few cases in which an anesthe- tic would defeat the object of the experiment, have been used. Not only are anesthetics de- sirable from humane motives (and the whole world gladly credits my profession with abun- dant charity and humanity), but it is self-evi- dent that dehcate, modern, technical operations require the absolutely complete relaxation of anesthesia, to say nothing of the possible acci- dents to the operators themselves from strug- gling animals. Besides this, as I shall show, 5 MEDICAL RESEARCH AND HUMAN WELFARE the knowledge derived from such researches, undertaken primarily for the benefit of hu- mans, has been and will be shared by countless animals year after year. Moreover, these researches have gradually enlarged our horizon so that now we recognize the "solidarity" of aU living things. That mysterious something, that wonderful reahty which we call "Life, " attains its highest and most complex development in the intel- lectual leaders of human thought and action, life also reaches down to the lowest monad and the lowest plants which simply exist and reproduce their kind. As we go down the series, the processes by which life is maintained become more and more simple; organs which perform precisely similar function in man, animal, or fish, such as the liver and the stomach, the heart and the limgs, are modified and at last may even dis- appear. Yet "Life," in its simplest activities of growth and reproduction, still is there. The lower and simpler forms of life possess fewer and fewer weapons for either defense or escape, but preserve their species by the enor- mous numbers of their offspring to counter- balance wholesale destruction by their natural 6 HUMAN WELFARE enemies. They also have the faculty of enor- mously rapid growth, not only in number, but in weight. Fish provide huge numbers of eggs, as in our f amiUar shad roe, and the lowest forms of life multiply with an almost incredible rapidity. The cholera bacillus divides into two, then four, eight, sixteen, and so on every twenty minutes, so that in seven hours, if given room enough and food enough, one bacillus woidd have produced four millions of descendants and in ten hours over two hundred millions. Each of these descendants possesses the same f ecim- dity as its parent. What the number would be in a week or a month staggers one's wildest imagination. The rate of growth of the silkworm in weight is equally astonishing. In the first thirty days after being hatched from the egg it increases in weight fifteen thousand times, or five hundred times its original weight every day. We can get a more impressive idea of what this means by comparing it with a human baby. Were the same rule to hold, a baby weighing seven pounds at birth would weigh thirty-five hun- dred pounds the very next day, and when a month old would weigh one hundred and five 7 MEDICAL RESEARCH AND HUMAN WELFARE thousand pounds, or over fifty "short tons," which, however, could hardly be called "short weight." If you will pardon the abominable but expressive argot of the street, that would be "some baby." But we may be somewhat consoled by remembering that both mother and nurse would be of corresponding elephan- tine bulk — made to "fit the job" as the ex- ponents of efficiency would say. But this is a gross, unimaginative way of look- ing at such a phenomenon. When we analyze it seriously, what a wonder-world we enter upon. How these little worms must feed, feed, feed! Think of the abounding life of each microscopic cell. Every one has to multiply itself five hun- dred times in every twenty-four hours. Yet all goes on in an orderly manner according to the law of its being, but with incredible swiftness, day after day. The only wonder is that in such speed there should not be errors and mistakes by the thousand. Yet Mother Natiu^e breeds true to her well-chosen model. And what superb work such a lowly, little worm does, for, presto ! and the yellow cocoon becomes the resplendent silk and the glossy satin. Animals closely resemble man not only in their structure and functions, but also in their 8 HUMAN WELFARE maladies. Their diseases are often identical with human diseases and are caused by the same bacteria; e.g., tuberculosis, tetanus, anthrax, etc. What is true of the animal world applies with modification even in the vegetable world. Plants carry on a modified respiration and circulation, they assimilate food, their wounds are healed, their diseases, even cancer itself, are analogous to the diseases of man and animals, they are susceptible to the same poisons, they live, they grow, they reproduce their kind, and they die. These are aU manifestations of that still, mysterious force which we call "Life." The physiology of animals and plants and the path- ology of their diseases throw light on the prob- lems of Human Physiology, Pathology, Health, Life, and Death. The man who, like Theobald Smith, devotes himself to the study of disease in many lower animals, has even a richer field to ctiltivate and may even have a broader vision than the man who hmits himself to the diseases of man alone. The latter haK of the nineteenth century has been the period of the most marvelous activity in research in every branch of science, astrono- omy, physics, chemistry, etc., and not less in medicine and surgery. This progress has been 9 MEDICAL RESEARCH AND HUMAN WELFARE made possible by the extensive use of the ex- perimental method more than by any other means. Through all of this period I have lived and I have been able to avail myself of its beneficent discoveries for the welfare of man- kind. I speak, therefore, of the things that I know and can vouch for personally, so far, at least, as surgery is concerned, and I have relia- able evidence of the truth in other departments of medicine. I took part in the old horribly fatal surgery of the Civil War and have borne a part in the struggle with infection and death until, thanks to Pasteur and Lister, we have emerged from a septic Purgatory into an aseptic Paradise. Only those who have lived through the transition pe- riod can fully appreciate the joy of deliverance from Death who formerly claimed, as his right, from five or ten to over ninety of our patients in every one hundred. Much of this work has been done in quiet, thoughtful, thorough, ingenious researches in laboratories. After repeated careful tests upon animals, the results have been applied to the amelioration of hmnan and animal diseases and the saving of human and animal life, as we shall see further on. 10 HUMAN WELFARE It is a spectacular feat to rush into a burning building and at the peril of limb and life to emerge, singed and bleeding, with a precious child in one's arms, rescued from a frightful death. It is lauded by the entire community and rightly so. But to work quietly in the laboratory, sm-rounded by deadly germs, and to discover the antitoxin of diphtheria, a remedy which will rescue not one child, but thousands upon thousands of children year after year, — is not this a feat deserving a greater reward than that accorded to physical bravery? Too often such a modest laborer in the Master's vineyard is forgotten or never even known. But even then he has his reward, hidden it may be in his own bosom and known and recognized by his Maker — a greater joy than gold or jewels can yield. In my early professional life, before such re- searches had been carried on, and the cause or the means of their prevention had been dis- covered, one single case of yellow fever, cholera, or plague in New York Harbor created terror in the whole city or even the whole nation, paralyzed commerce, and caused a wholesale exodus and widespread, most annoying quar- antine. Now such a case scarcely wins a head- 11 MEDICAL EESEARCH AND HUMAN WELFARE line on the first page of the morning papers, so complete and so justified is the confidence pf the community in the abiHty of scientific medi- cine to cope with and to conquer the disease. Quarantine is no longer what its name declares — a detention of forty days. In fact it rarely is necessary, and when necessary is short and shorn of the horrors of a century ago. Even smallpox no longer sends everybody to the railroad, the steamship, and the auto, but sends them straight to the doctor, who quickly gives them the protection of a simple vaccina- tion. I bring you, therefore, a message of joy and good cheer, of wonderful achievement in every department of medicine and wonderful contri- butions to Human Welfare. A NEW TYPE OF SURGEON Experimental research has bred a new type of doctor and especially a new type of surgeon. Among the earlier pioneers were Harvey (1578- 1657), Haller and John Hunter, both nearly contemporaries with Washington. But with the advent of Pasteur and Lister there opened the vast and virgin field of illimitable fertility 12 A NEW TYPE OF SURGEON in the new science of Bacteriology. Later, Fritsch and Hitzig, Ferrier and Horsley, whose recent death in Mesopotamia was a world-wide calamity, and others in Europe; Senn, Hal- sted. Gushing, Crile, and others in America have been the modern happy leaders The older clinical siu-geons observed shrewdly the phenomena of various diseases and in- juries in the living, and the final phenomena in the dead, assembled in statistics the results of differing methods of treatment, including varied operative procedures, or of abstention from operation, and drew their final conclusions as to which method promised the best results. The new type of surgeons, relatively few in number but potent in influence, hungering and thirsting for broader and more complete knowl- edge, restrict their actual surgical work so as to carry on researches in bacteriology, physiology, physiological chemistry, and physiological phy- sics, and even as Carrel has recently done in what might be called "mathematical surgery," with its mysterious equations. Carrel can now predict to 'a day when a wound will be com- pletely healed with almost the accuracy of an astronomer in predicting an ecUpse. The new surgeon pursues his studies in the 13 MEDICAL RESEARCH AND HUMAN WELFARE laboratory as well as at the bedside and in the operating-room. He employs the second, the experimental, method of research as I have just described it. He tries new ways of operat- ing or devises entirely new operations, which often require him to invent wholly new instru- ments. When he has discovered any improved method or new operation and fully tested it in animals, then and only then does he ven- ture to apply it systematically both to animals and to man. Thus, by intensive study and in a brief time have been introduced wholly new methods and multitudes of new and life-saving operations for the lessening of misery and res- toration to health. The new surgery of the last forty years, with which many of you are reasonably familiar, has been the abounding harvest of these devoted Servants of Human- ity. Were I a physician, an obstetrician, a physi- ologist, an ophthalmologist, or other such spe- cialist, I could make a similar showing. In- deed, before I end these lectures I shall have poached upon the preserves of a number of these my colleagues in our laborious but victo- rious campaign against Disease and Death. 14 ANESTHESIA ANESTHESIA It is almost superfluous for me to call your attention to one of the greatest boons ever conferred on suffering humanity — the abolitiou of the horrible pain attending surgical opera- tions. This has done far more than merely abolish such pains. It has made possible pro- longed and dehcately difficult operations which require the absolute immobihty of the patient. Imagine an abdominal section, such as is now common, with removal of a portion of the in- testine followed by uniting the two open ends so carefully and so securely that no fatal leak- age of a single drop shall occur. Such an op- eration, by reason of extensive adhesions or from other causes, may easily require an hour. Sometimes such an operation may require one and a half, or, though rarely, even two, hours. Could flesh and blood lie quietly, still as a sta- tue, while such an operation was being done.'* But beside the drugs for general anesthesia. Medical Research within the last thirty years has discovered means by which local anesthesia can be attained; that is to say, the part to be operated on is made entirely insensible to pain while the patient himself remains entirely con- 15 MEDICAL RESEARCH AND HUMAN WELFARE scious. Nearly everybody has an innate aver- sion to loss of consciousness per se. This is wholly apart from fear. Various methods, by means of freezing, or the subcutaneous injection of cer- tain drugs, such as cocain, novocain, eucain, etc., are employed. Besides their subcutaneous use these same drugs can be injected into the sheath of the spinal cord by lumbar puncture, thus making all the body below the waist in- sensible to pain. It is not within the scope of these lectures to assess the relative values and the dangers of these various methods, but only to point out how the marvelous resources of science have been mobilized for the welfare and comfort of mankind and of animals. Happy, indeed, are not only the surgeons, but also those engaged in experimental research, that investi- gations, such as Claude Bernard, Magendie, and others were obUged to carry on when anesthet- ics were unknown, and far more difficult and delicate operations than they even dreamed of, can now be done, and are done, painlessly. The first public use of ether was at the Massa- chusetts General Hospital on October 16, 1846. Chloroform was first used on November 17, 1847. About 1867 the use of nitrous oxid came into common use in dentistry, and during the 16 ANESTHESIA last ten to fifteen years has been largely used in surgery. All of these events have taken place during nay own lifetime. Ether and chloroform were introduced during my boyhood; nitrous oxid and all methods of local and spinal anes- thesia have been introduced during my pro- fessional lifetime. When I have heard my old master in surgery, the elder Gross, and other siu-geons of his generation, tell of the way in which patients were bound hand and foot and held in the tight grip of four strong orderlies to secure a partial quietude, and of the almost frantic involuntary struggles of patients, and their screams of agony, in the pre-anesthetic days, I have thanked God that I was born too late to participate in such horrors. Then he was the best surgeon who could amputate a limb in five or ten seconds less than any other surgeon. The painstaking, accurate, artistic siu-gery, such as to-day is achieved by every good surgeon, was absolutely unthinkable even to the most dexterous surgeons in the first half of the nineteenth century. It had to be what, without casting reproach on our predecessors, one may call "slap-dash surgery" or none — ■ and "slap-dash surgery" might easily be in- accurate surgery and do great harm. 17 MEDICAL RESEABCH AND HUMAN WELFARE INSTRUaiENTS OF PRECISION Among the most important means by which Medical Research is promoted are instruments of precision. When I studied medicine, a few, in fact a very few, doctors possessed a micro- scope. Strange to say, the medical colleges themselves had none. Only those private stu- dents who were so fortunate as to have the most enlightened preceptors ever saw a microscope, much less had the chance to use one. I doubt if there were half a dozen thermometers and hypodermic syringes in the whole Army of the Potomac in the Civil War. A number of years passed before self-registering thermome- ters were made. The first short clinical ther- mometer I ever saw was brought to me from London by Weir Mitchell in 1876. The first book in medical thermometry was published by Wiinderlich in 1869, four years after the Civil War closed. Imagine the plight of the mother of a family to-day without a thermometer! Now, for experimental researches, there are electric thermometers by which one can make continuous observations in a hospital and re- cord them at' stations a mile away from the patient and the instrument. Mosso has de- 18 INSTRUMENTS OF PRECISION vised an apparatus on which the patient lies, so delicately balanced that if he is spoken to, or a door is closed with a slight jar, even during his sleep, the brain is roused to activity — more blood is swiftly supplied to the brain, the head becomes heavier, and that end of the appa- ratus falls. How and why, you ask, does this blood leave other parts of the body and go to the head? In man and animals, in close proximity to the jugular vein in the neck, is the sympathetic nerve — a slender, nervous cord, the use of which nobody knew. Just before the Civil War Claude Bernard cut this cord, " just to see what would happen." He found that the pupil of the eye on the same side contracted to a pin-point, the blood vessels of the ear of a cat or a rabbit dilated and the ear was much redder and hot- ter. This simple experiment opened the door to a vast store of knowledge. The sympathetic nerve is the means by which automatic changes are effected all over the body: changes which we cannot initiate and cannot arrest — changes which are essential to well being. This nerve controls the size of the pupil so that, on going out into bright sunlight, in a few moments it protects the eye from injury by contracting 19 MEDICAL RESEARCH AND HUMAN WELFARE the pupil. On going into a darkened room it dilates the pupil so that enough light enters the eye for you to see. This Kttle nerve spreads out over every blood vessel all over the body, enlarges its diameter if blood is needed in any organ and lessens their caliber when the need has passed. When you eat a meal the stomach becomes redder than the most inflamed eye you ever saw. All its blood vessels are dilated to their maximum to enable the glands of the stomach to secrete enough gastric juice for digestion. When this is accomplished the blood vessels narrow and are scarcely visible. When you blush for shame or grow pale with fear, this slender, nervous cord has produced a dilata- tion or a contraction of the blood vessels of your face and neck, according to your emotion. When you think, you need more blood in your brain. You do not, indeed you cannot, order it to go there and you do not have to keep up ordering it there. This is done for you au- tomatically. Hence, even in your sleep, as we have seen, a voice, the jar of a closing door, may not even waken you, but your slender, sympathetic nerve never goes to sleep. It is ever on the alert to help you. 20 INSTRUMENTS OF PRECISION When you are wounded the same obedient nerve automatically dilates the blood vessels, carrying the extra blood needed for repair, and the area around the wound is reddened and is hotter than the unwounded part. What a won- derfully beneficent mechanism this is — how useful — how indispensable 1 And we knew nothing of all this astonishing action, so important in health and disease, in physiology, pathology, surgery, every depart- ment of medicine, until Bernard cut this little cord in the neck, to see what would happen! If I only had the time I could tell you other equally interesting, in fact fascinating, stories of many discoveries in the physiology of diges- tion, of respiration, in the physiological chem- istry of the blood and of the normal secretions, and in pathology or the changes brought about by disease. Oiu" knowledge of all these subjects, instead of being the shrewd but uncertain guesses of close observers, has become exact and positive knowledge upon which we found not only our diagnosis, but our treatment. It is quite safe to say that in practically all diseases, save perhaps cancer, the death-rate is steadily and often rapidly lessening as a result of such scientific research. And we doctors who hve 21 MEDICAL RESEARCH AND HUMAN WELFARE by sickness and accident are the foremost in these researches and rejoice with joy unspeak- able at every advance in the conquest of Dis- ease and Death! Many of my hearers are now fanuliar with the blood-pressure apparatus which in the last few years has won its place in diagnosis. Whole books are devoted to this one subject. In ani- mals we can ascertain this pressure far more accurately than in man, for we connect the ap- paratus directly with the blood current in an artery or a vein. The pulse-beats and its curves are minutely analyzed by comphcated instru- ments and recorded on smoked paper on a slowly revolving drum. When, by reason of shock and loss of blood, the blood pressure during an operation falls so low as to be dangerous, we now can make a transfusion of blood. In certain diseases, as you all know from the daily papers, transfusion is also frequently resorted to. What you do not know is the long series of experimental re- searches on animals made by many surgeons, which has converted, what was so dangerous an operation that it had been abandoned, into a safe one. Now, thanks especially to the re- searches of that genius, Carrel, transfusion has INSTRUMENTS OF PRECISION] become so safe that it is used even in cases of newborn babies who are bleeding to death, and are changed as by a miracle from dying babies into thriving and healthy babies. The color of the blood is sometimes a very important element in deciding for or against an operation, or for or against giving an anesthetic. It can easily be determined by an instrument to measure the color of the blood. Its freezing point, the time necessary for it to clot, its bac- teriology, and its chemistry all require constant research and are all constantly increasing in value. But the instrumental study of the heart has progressed further than even the most vivid imagination could portray. By the X-rays we can see its size and witness its beating — a mar- velous automatic act, the continuance of which dominates our existence from even before birth down to the last moment of life. Very recent improvements in the instruments now enable us to obtain X-ray pictures showing the action of each auricle and each ventricle separately. All muscular action — note this fact — all muscular action generates slight currents of electricity. Therefore, the muscular contrac- tion of the walls of these four cavities of the MEDICAL RESEARCH AND HUMAN WELFARE heart generate slight currents of electricity. Such a current, slight as it is, is suflScient to actuate another marvelously delicate instru- ment, the electro-cardiograph. By this we can record on a revolving drum the phases of move- ment of each of these four cavities. * The anatomists have discovered, at a point where the superior vena cava empties all the blood of the head, neck, and arms into the right auricle, a special network of muscles and nerves which Thomas Lewis, of London, has called the "pacemaker" of the heart, for the contractions of the heart are started by it. His, the German anatomist, some years ago discovered a similar small bundle of muscular and nervous fibers in the furrow between the auricles and ventricles which regulates the contractions of the ventri- cles. The auricles and ventricles, to use a rough but very simple simile, do not contract all four at once, as we would suppose, but in a rhythmical succession Uke the four feet of a horse. The "pacemaker" starts and the "bun- dle of His" regulates the successive rhythmi- cal contractions of these four cavities. If the passage of stimuli, starting from these two points or foci, is interfered with, a certain num- ber of impulses may be blocked and, for exam- 24 INSTRUMENTS OF PRECISION pie, only one in two may get through. If the impulses are entirely blocked, the am-icles and ventricles beat wildly and entirely independ- ently of each other. These interferences are, therefore, called respectively "partial" and "complete heart block." By the electro-cardi- ograph we can study minutely every phase of such movements down to what occurs in the fiftieth part of a second. A diagnosis which it is absolutely impossible to make by touch and ear is positively and accurately observed by such a wonderful instrument of precision. It gives the very earliest warning of danger, long before our clumsy natural senses can find out that anything is wrong. By the X-ray, as you know, we can now discover foreign bodies in the windpipe and lungs, in the esophagus, stomach, and intestines, stones in the gall bladder, kidneys, m-eter, and urinary bladder; can see an artery whose walls have become hardened by arterio-sclerosis, can see foreign bodies and tumors in the brain, and can see even the convolutions of the brain, fractures, dislocations, tumors, and abscesses in bones, unsuspected abscesses at the roots of the teeth, tuberculous cavities in the lungs, cancer of the stomach, etc. By mixing bismuth with 25 MEDICAL RESEARCH AND HUMAN WELFARE the food (bismuth is impervious to X-rays and so casts a shadow) we can follow the food from the stomach through theintestines. By this method Cannon, of Harvard, has shown the physical effect of fear and other emotions in arresting the digestive processes. In 1891 Quincke, of Kiel, first introduced "lumbar puncture." A long needle attached to a hypodermic syringe is inserted within the sheath of the spinal cord, but below the cord itself, in the small of the back or "lumbar" regions and some of the fluid which bathes the cord and the brain is obtained. The pres- sure of this cerebro-spinal fluid is important and can be estimated, and the presence or ab- sence of any foreign substance, such as blood, pus, certain bacteria, etc., can be determined by the microscope. An unsuspected fracture of the base of the skull may declare itself by such blood. No diagnosis of cerebro-spinal meningitis is accepted at present as scientifi- cally proved except by Imnbar pxmcture. With- out this a large percentage of mistakes occur. All of you are familiar with at least a few of the ingenious "scopes" by which we can look into various cavities of the body. Helmholtz, of Berhn, that wonderful genius, first showed 26. INSTRUMENTS OF PRECISION the way by devising tlie "ophthalmoscope" in 1851. In 1858 Czermak, of Prague, devised the "laryngoscope." This was so new when I en- tered the Jefferson Medical College in 1860 that to my almost incredulous inquiry "whether it was really possible, as Green, of St. Louis, as- serted, actually to see the vocal chords in a living patient," my preceptor, later the dis- tinguished ProfessOT J. M. DaCosta, replied rather hesitatingly that he "thought" it was! Now we look not only into the interior of the eye and the larynx, but down into the bronchi, into the esophagus, and even inspect the in- side of the stomach, the bladder, and every other hollow organ accessible from the exterior. To explain how great has been the advance in knowledge of function and in diagnosis and treatment by reason of the positive informa- tion obtained by these various instruments of precision, and how much our patients have benefited by this new knowledge would take me too far afield, but in a general way I may say that to them is due practically, I should say seventy-five per cent of our present knowl- edge of the diseases of the organs susceptible to this method of examination. Without these ingenious instruments physiologists, physi- 87 MEDICAL KESEARCH AND HUMAN WELFARE cians, and the surgeons and specialists would be as utterly helpless as if in our community life our railroads and steamships, our telegraphs and telephones were suddenly abolished. Turning now to individual medical re- searches which have made great contributions to Human Welfare, I must content myself with the story of only a few of the most notable, for to recite the whole long catalogue would expand these lectures far beyond reasonable limits for even your friendly indulgence. My "Bill of Particulars" to which I now turn must therefore be a restricted one. Two great achievements in modern medicine before my professional studies began in 1860, were vaccination in 1796 by Edward Jenner, and anesthesia, first introduced publicly to the profession on October 16, 1846, when I was over nine years old, by Morton and Warren, at the Massachusetts General Hospital. BACTERIOLOGY The third great achievement was the discov- ery of the causal relation of bacteria to many diseases. Thus arose a new science — "Bac- 38 PASTEUR'S AND LISTER'S ACHIEVEMENTS teriology " — the most important discovery ever made in pathology. It would scarcely be an exaggeration to say that Bacteriology is the most important discovery ever made in any department of medicine, for upon its revela- tions hang most of our modern surgery, and a very large part of the advances in modern medicine and in modern obstetrics. Bacteri- ology is also the foundation of a very lai^e part of modern sanitary science and of much of our agricultural success. While bacteria had been named and known for many years, they had not been classified and coordinated into a science until about thirty years ago. The earliest use of the word "Bacte- riology " dates only from 1884. With the rise and development of Bacteriology must always be associated three illustrious names : Pasteur, Lister, and Koch; especially the first two. PASTEUR'S AND LISTER'S ACHIEVEMENTS— SPONTANEOUS GENERATION I was in Paris as a student in 1865 when the scientific world was stirred to its depths by the great contest over spontaneous generation. One of my teachers was a son of Pouchet, Pas- 29 MEDICAL RESEARCH AND HUMAN WELFARE teur's principal opponent. Pouchet published experiment after experiment in which it seemed impossible at first sight to explain how the liv- ing organisms arose in his sterile flasks except by spontaneous generation; but with marvel- ous genius Pasteur always found some un- guarded portal of entrance. For instance, Pas- teur not only sterilized the contents of his flasks and then sealed them, while boiling, but high up in the Alps, held each flask above his head when he broke the neck of the flask with sterile forceps. Even the direction of the wind was evoked in his behalf. If the wind blew over the opened flask first and then over his body, no infection followed. If he turned around so that the wind swept past his body first and then over the opened flasks, it carried germs from his person and his clothing, and infection followed. Such minute precautions are now the A B C of Bacteriology — then they were wholly new and even derided as unnecessarily meticulous. Up to the time of Pasteur's experiments putrefaction was believed to result from the action of the oxygen of the air on the putres- cible substance. Pasteur, and later Lister, by as simple an experiment as that of Columbus 30 PASTEUR'S AND LISTER'S ACHIEVEMENTS and the egg, proved the falsity of this be- lief. Lister filled four glass flasks one third full of urine, a most easily and quickly putrescible fluid. He then drew out the necks of the flasks into fine tubes less than one twelfth of an inch in diameter. The neck of one flask was left ver- tical and open to the air. The necks of the other three were bent downwards at various angles but were left open. Each flask was then boiled. This sterilized the inside of the flask as well as the urine. All four were kept together in the laboratory. The air with its oxygen, as the night grew colder, was slowly drawn into all four flasks and slowly expelled as the air grew warmer in the morning. In a short time the flask with a straight neck underwent putrefac- tion. The three with necks bent downward, but freely open to the air, remained perfectly free from putrefaction iorfour years. The explana- tion is clear. The germs in the air drawn into the flask with the vertical straight neck fell directly into the fluid and caused its speedy putrefaction. In the air drawn into the flasks with bent necks, the germs being slightly heav- ier than air, settled on the sides of the neck of the flask and never reached the fluid. The oxygen entered all flasks alike. 31 MEDICAL RESEARCH AND HUMAN WELFARE The final result of many experiments and prolonged controversy was that the impossibil- ity of spontaneous generation was absolutely established. Omne vivum e vivo was proved to be true. Only life can produce life. Lister, and especially Pasteur, discovered, proved, and compelled the acceptance of the germ theory as applied to putrefaction and opened the way to the means of its prevention. The same principles apply to the causation of infection in wounds and of many diseases in animals and man and their prevention or cure. It is a fascinating story. The "Life of Pas- teur," by his son-in-law, Vallery Radot, is the most inspiring scientific biography I know. Its title in the earlier editions wins us by its wit and modesty and is really untranslatable from the spirituelle French into our clumsier though virile English: "Louis Pasteur. La Vie d'un Savant par un Ignorant." Pasteur was born in 1822 and died in 1895 at the age of seventy-three. About the middle of the nineteenth century, when he was in the early thirties, we "did not know much more of the actual causes of the great scourges of the race, the plagues, the fevers, and the pesti- lences, than did the Greeks," as Osier has well 32 PASTEUR'S LIFE AND WORK said. He then continues: "Here comes in Pas- teur's great work. Before him Egyptian dark- ness; with his advent a light that brightens more and more as the years give us ever fuller knowledge." PASTEUR'S LIFE AND WORK Pasteur began his life-work in crystallogra- phy and by his exact observation explained why two kinds of tartaric acid turned polar- ized light the one to the right and the other to the left. All through his life he longed to return to his "dear crystals." But God had mapped out a far more beneficent career for this Apostle of Science. He studied the repair of wounds in crystals. Breaking off a piece from an octahedral crystal he replaced the wounded crystal in the mother liquor. After a time the wound was healed and the crystal was again perfect. Next he placed one of the salts of racemic acid — a compound (as he had already dis- covered) composed of the right and left polar- izing tartaric acids — in the ordinary condi- tions for fermentation. Only the dextro-tar- taric — the right polarizing — acid fermented. 33 MEDICAL RESEARCH AND HUMAN WELFARE His explanation was that the living ferments attacked and fed upon only this one form of the acid. Per contra, if he cultivated a little penicillium glaucum — a lowly fungus — on the surface of ashes with one of the other forms of tartaric acid, there was produced only the left polarizing tartaric acid. These were phe- nomena of life of a physiological order. Thus was he led by his crystals to study the changes produced by the lowest forms of living beings in physiological and finally in pathological conditions in animals and man. Thus Bacteri- ology, after multipUed labors and experiments, was born. The year 1855 found him in the University of Lillcj a "mere chemist," as his adversaries called him. He knew nothing of medicine, and never became an M.D, Yet we doctors all pay him enduring homage as one of the greatest of our guild — truly an "Honorary Member." Lille was a town of great breweries and Pas- teur's services were soon enlisted in the study of the diseases of beer, which led him again to study fermentation in all its varied forms in beer, wines, vinegar, alcohol, sour milk, and rancid butter. He carried over the exact meth-^ ods of the chemist, but along with it the im^- S4 PASTEUR'S LIFE AND WORK nation of the seer, into this new realm of Biol- ogy. He disproved the then prevalent belief of Berzelius and Liebig that fermentation was due to a so-called "catalytic" influence of a certain substance — acting simply by its presence. I learned this catalytic theory at Brown and had to unlearn it. Pasteur proved conclusively that fermentation was due in all cases to a living substance, such as the yeast plant, or the "mother" of vinegar, or similar vegetable organisms in all fermentations. These studies produced in his mind the idea that diseases of humans like diseases in beer, in wine, in milk, in butter, might be due to micro- scopic germs floating in the atmosphere, an idea which was to fructify into great discover- ies, destined in the hands of Lister to revolu- tionize mediciae, surgery, and obstetrics, and to prove of untold value to man and animals. The key to Pasteur's methods is found in his dictum, "In experimental science it is always a mistake not to doubt, when facts do not com- pel you to affirm." Then, in Paris, followed the contest over spontaneous generation, to which I have al- ready alluded. 35 MEDICAL RESEARCH AND HUMAN WELFARE THE SILKWOKM Next, Pasteur's genius was sought in an efifort to save the great silk industry of France. This industry was threatened with extinc- tion by an extraordinary and inexpHcable mortaUty of the silkworms. He had "never even touched a silkworm." But he was equal to the task. After a long and laborious search, with many puzzling apparent contradictions, he finally discovered that the silkworms had been destroyed by two diseases. One of these, named "p^brine," was caused by pecuhar germs called "corpuscles" and the other, called "flachery," by an infective micro- organism. Then the problem was solved. The eggs of all the silkworms in whose bodies the "cor- puscles" of "p6brine" were discovered were destroyed and only the eggs of healthy worms were used for breeding. Ordinary precautions against infection prevented "flachery." The latter was not hereditary, the former was. A national calamity was averted. In 1868, when only forty-six years of age, Pasteur's labors and even his life were threat- ened with complete collapse. His entire left side 86 ANTHRAX was suddenly paralyzed. Gradually, however, he recovered and, wonderful to relate, his very best work was done during the next twenty years. While he never entirely regained the use of the paralyzed side and always had a bodily limp, yet, fortunately, his active mind never limped, but strode onward conquering and to conquer. ANTHKAX Another of his great achievements which again blessed his always idolized country was soon accomplished — the conquest of an- thrax. This is a very ancient disease. Is is be- lieved to have been the murrain of the Egyp- tian plagues. It is a very fatal disease in men as well as in cattle. In Italy from 1890 to 1902 the annual toll of human lives was 2100, and in Russia from 1904 to 1909 it cost as many as 16,000 human lives a year. Fortunately with us cases of the disease are rare. Anthrax was then devastating the sheep and cattle of France and costing also many human lives. Animals grazing over certain fields sud- denly fell ill and quickly died. Pasteur proved that even from buried carcasses of animals 37 o o o o o f5 ^ 13 a ■3 P3 a >> a en "d t- o3 ^ '0 C3 ■u -a >. >i -fj x: ^ M »o TS -0 .3 1 g ■3 .B ■t^ -i-> tn M cc HH !>3 1) ^ -fj 4J fl =5 1^ as '§ ^ . '3 cd "3 M 4) -3 S 't^ -M 0. p 0. ID a ^ a d cS H ANTHRAX a second, from this a third, and so on up to one hundred generations, and found that the one hundredth culture would kill as certainly as an injection of the blood itself. Among other animals hens had been inocu- lated with anthrax germs, but they always sur- vived. Pasteur became interested in this curi- ous exception and finally found the reason for their exemption. The normal temperature of the hen is several degrees above that of sheep and cattle. This higher temperature he be- lieved prevented the growth of the anthrax baciUi. To test this important point in the life history of the bacilli, he inoculated hens and then lowered their temperature by cold baths. This so reduced the temperature of the hens that the anthrax bacilli could multiply and the hens died the next day. A few degrees of tempera- ture more or less held the balance between life and death. One ingenious experiment clinched his argu- ment. A hen was inoculated with anthrax and held in a cold bath until it was evidently very ill with anthrax. Then the hen was taken out of the bath, dried, wrapped up in cotton, and re- covered entirely. Her temperature fell in the bath so that the anthrax bacteria grew and 39 MEDICAL RESEARCH :aND HUMAN WELFARE made her ill, but when her temperature rose after removal from the bath the bacteria were killed and she recovered. It is startling for us humans, with all our physical and mental superiority, to find that we too are at the mercy of such ahnost infinitesi- mal lowly plants which break through'and steal our health and often our very lives. Happily, however, Pasteur showed the way to escape from this danger. I can give you a personal in- stance of the speed and violence of the invasion of such bacteria. Many years ago, at a -post- mortem,, I pricked my thumb with a needle very slightly. In fact I hardly knew that I had pricked myself. In eight hours I began to feel chilly, in twenty hours my temperature was 105°. I barely escaped with my life. Note what a temperature of 105° means. It means that my one hundred and fifty pounds of flesh and blood had the temperature raised from 97.5° F. to 105° F. or 7.5°; and not only was it raised to that height, but it would have been kept there or would have gone even higher until death supervened. But modern surgery came quickly to my aid. Under ether the thumb was widely opened and thoroughly dis- infected and my life was saved. 40 ANTHRAX Pasteur's last triumphant experiment as to anthrax was dramatic. He had discovered by many experiments that the anthrax bacteria could be cultivated at 42° or 43° C, but in a weakened form; i.e., they never develop "spores," or, as I may call them, "seeds." At 45° C. the bacteria themselves could no longer be cultivated. You see now the value of his experiments on hens! He was now ready for the experimentum crucis. He proposed by this attenuated virus to vac- cinate twenty-five healthy sheep against an- thrax. Then later to inoculate these twenty-five vaccinated sheep and twenty-five other healthy but unvaccinated sheep with a virulent virus of anthrax. He predicted that by a certain day every one of the twenty-five vaccinated sheep would escape death and every one of the twenty-five unprotected sheep would die. It was, indeed, a decisive test. One of his oppo- nents said: "He must succeed. . . . Let M. Pas- teur not forget that the Tarpeian Rock is near the Capitol." On May 5, 1882, at the Pouilly le Fort farm near Melun, a large crowd of people, farmers, doctors, veterinary surgeons, and others, as- sembled at this memorable rendezvous to see 41 MEDICAL RESEARCH AND HUMAN WELFARE Pasteur's vindication or his humiliation. The first twenty-five sheep were then inoculated with the protective vaccine. On May 17 a second protective inoculation was given to the same twenty-five sheep. On May 31 the final inoculation, this being an anthrax virus of full strength, was given to all the fifty sheep, twenty- five protected and twenty-five unprotected. By June 5 he declared that all the unprotected twenty-five would be dead and the twenty-five protected would all be alive. On June 2, three days earlier than his pre- dicted date, when Pasteur arrived, he was loudly acclaimed the victor, for there already lay the dead carcasses of twenty-two of the un- protected sheep and the other three were dying, while all the twenty-five vaccinated sheep were in good health! All France rightly rang with his praises. The method has been adopted everywhere, and by this vicarious sacrifice of a few sheep countless flocks and herds have been rescued from the suffering and death to which they were doomed by Nature's cruel experiments. Their owners have been saved from enormous pecuniary loss and millions of human beings have been pro- vided with so much more wool, more hides, and PUERPERAL FEVER more meat as a sequel to that memorable day. Our enterprising and most useful Agricultural Department has discovered a serum even more potent as an antidote than even Pasteur's. To insure and standardize its strength it is always tested first on rabbits. PUERPERAL FEVER But a still greater triumph marked these same years — the conquest of puerperal or childbed fever. This fever is the most humili- ating incident in the history of medicine. In these antiseptic days the ravages of this fell disease are almost unknovra. But a quarter of a century after the ink had dried on my own medical diploma, the obstetrician — who should usher in a new life — was too often a sower of the seeds of death. In the Pennsylvania Hospital from 1803 to 1833 every eighteenth mother left her newborn baby motherless. In 1872 Lusk, of New York, reported an epidemic in which one mother out of every five died! In my own early professional life I knew of case after case proving fatal, and in some epidemics the accoucheur for a long in- terval had to relinquish practice entirely, for MEDICAL RESEARCH AND HUMAN WELFARE Death always peered over his shoulder and slew every fifth, fourth, third, even every sec- ond, mother. A mortality as high as fifty-seven mothers out of every hundred has been re- corded! Its mystery, like the pestilence that walketh in darkness and the destruction that wasteth at noonday, spread fear among doctors and expectant mothers. Oliver Wendell Holmes in 1843 declared that the doctors and nurses themselves carried the dreaded infection, but how or why no one knew. In 1861 Semmelweiss, in Vienna, preached the gospel of cleanliness anew, but was derided and even ostracized. Pasteur, however, compelled a hearing throughout the world: what is better, he was the victor. In 1879, — less than forty years ago, — in a debate at the Paris Academy of Medicine, the leaders were at odds as to the cause of this fever and were totally ignorant of any means for pre- venting it. Suddenly interrupting an eloquent colleague discussing the various possible causes, Pasteur declared that puerperal fever was of bacterial origin, and was carried by the doctors and nurses. His colleague retorted that he feared that this strange microbe would never be found. Thereupon Pasteur at once stepped 44 CHICKEN CHOLERA to the blackboard, and drawing what we know as the streptococcus, said, "Voici la figure!" (There it is!) And there it was, indeed! And what has been the result of the re- searches by which Pasteur demonstrated the cause of childbed fever and how to aboUsh it? Every wife and every husband should know these facts and treasure Pasteur's memory in their hearts. Instead of every eighteenth, every fifth, or more than every second mother lost to her husband, her children, and the community, puerperal fever now slays only one mother in three hundred to even so low a rate as one mother in twelve hundred and fifty! Verily Pasteur was one of God's best gifts to Human- ity. CHICKEN CHOLERA Chicken cholera was a serious malady in France until after Pasteur's researches in 1882. Healthy fowls would suddenly sicken and die within a day or two, again from a mysterious disease without apparent cause. Once more Pasteur waved his wand and light shone in the darkness. He had discovered the germ, and by inoculating healthy hens, was searching for 45 MEDICAL RESEARCH AND HUMAN WELFARE a vaccine against it similar to the anthrax vac- cine. One day by accident he injected a cultiu-e from an old flask standing on a shelf in the laboratory and forgotten for a few weeks. The hens thus accidentally inoculated with this old virus sickened, recovered, and when tested with strong virus, withstood it and remained well. The vaccine was found. To mediocrity the happy accident that it was an old culture would have been merely a curious fact to be recorded. To genius it was a fertile idea to be explained and developed by experiment. We shall see this in a moment when considering hydrophobia. SWINE PLAGUE Next swine plague was investigated. "Send me one thousand francs," he wrote. "I have but three himdred francs left. . . . Pigs are expensive and we are killing a great many." "Killing a great many?" True. But how many thousands and hundreds of thousands has he saved by the sacrifice of the few score which he called "many"? It is the old story of the fifty sheep at Pouilly le Fort farm — a vicarious sacrifice sanctioned both by science and hu- manity, 46 HYDROPHOBIA HYDROPHOBIA I have only time to record one other service by Pasteur; but this is his notable victory over that horrible disease called rabies in animals and hydrophobia in man. Pasteur's mind had been irresistibly drawn to this malady by its mysterious nature and by his previous studies. In 1881 he began his researches. His investi- gations showed him that, whatever its nature (and this germ, mark you, hke that of yellow fever, has not even now been discovered), this virus centered in the spinal cord, especially in its upper end. After the bite of the rabid animal there was always a long period before the disease would develop — a period of weeks and even months of anxiety and suspense. Finally Pasteur tried the experiment of inject- ing some of the upper end of the spinal cord of a dog dead of rabies directly into the brain of a rabbit, from that rabbit to another, and to another, untU, instead of months of uncertain waiting, he was able to induce the disease in fourteen days and later in seven days, thus greatly facilitating its study. Remembering his remarkable experience in the weakening of the virus of chicken cholera and of anthrax by time, 47 MEDICAL RESEABCH AND HUMAN WELFARE he now placed the spinal cords of a number of dogs suspended by a thread in sterile sealed jars. In the bottom of the jars was some caus- tic potash to absorb the moisture and facilitate the drying. By many experiments on various animals he at last found that a cord which had hung in such a jar for two weeks could be in- jected into the brain of animals and that rabies did not follow. Then he tested on the same dog material from a cord after thirteen days of drying, later from a cord which had been dry- ing for twelve days, and so on until the experi- mental dog was so fully protected that even the strongest fresh virus had no effect. Victory again was his. But only a victory over the disease in animals. Dare he use it in humans? "My hand will tremble," said he, "when I go on to mankind." He shrank almost in terror from injecting into a human being the virus of rabies. What if perchance it should give the patient an attack for which he would be responsible? At last Nature forced his hand. On July 6, 1885, the mother of an Alsatian boy of nine, named Joseph Meister, brought him to Pas- teur. Two days earlier he had been attacked by a rabid dog and received fourteen wounds. 48 HYDROPHOBIA Anxious to help the child, yet fearful of harm- ing him, after consulting with some friends, Pasteur began the treatment with fear and trembling. First he used a cord dried for four- teen days, then one dried for thirteen days, then for twelve days, and so on. But what anxious days and nights he spent! He could neither work nor sleep. He was beset even in his dreams by visions of the child in the grasp of the demon of hydrophobia. On July 16, still with fear and trembling, he injected finally material from a cord which had been dried for only one day. Some of the same cord injected into rabbits was followed by rabies in the rab- bits. But the boy remained well. Gradually his fears subsided as time went on and the boy still remained perfectly well. His final triumph was achieved. In the following October another boy was inoculated six days after being bitten. He too recovered. From thenceforward the remedy was used more and more freely with lessening fears and growing hopes. Before Pasteur, of one hundred persons bit- ten by rabid and supposed rabid animals, dogs, wolves, foxes, etc., about sixteen fell victims to hydrophobia. Of these sixteen every one died. 49 MEDICAL RESEARCH AND HUMAN WELFARE There is not, I think, a single well-authenti- cated case of recovery after the disease has developed. The mortality of all those bitten is, therefore, about sixteen per cent — the mor- tality in actual cases of the disease is one hun- dred per cent. From 1885 to 1905 — twenty years — there were treated at the Pasteur Institute over twenty thousand persons, and the mortality for the last few years has been 0.32 per cent; that is to say, nearly fifty times less than in the days before Pasteur. In 1915 of six hundred and fifty-four persons bitten, instead of one hundred and five deaths, — the number which would have occurred before Pasteur, — there was only one death! Naturally the patriotic fervor of the French quickly led to the establishment in Paris of an "Institut Pasteur," founded by popular sub- scription of over two and a half milUon francs. Among the names of the donors stands that of the httle Alsatian boy, Joseph Meister, whose gift was the greatest of all those cast into the treasury. All over the world Pasteur Insti- tutes have been established, and their record of success everywhere has been practically the same. Muzzling of all dogs would banish hydro- 50 HYDROPHOBIA phobia. How cruel we are to refuse to cause slight discomfort to dogs and thereby to sacri- fice human lives. No more devoted patriot than Pasteur ex- isted. His efforts were always for France. "Nothing would have consoled me," said he of his vaccine against anthrax, "if this dis- covery had not been a French discovery." His whole life is redolent with patriotism. When he was informed that a village in Algeria had been named after him, he wrote: "When a child of that village asks what was the origin of the name, I should like the schoolmaster to teU him simply that it is the name of a French- man who loved France very much and who by serving her has contributed to the good of humanity." The same lofty patriotism has breathed a new Ufe into the heart of France to-day. Lately, when the family and friends of a young recruit about to leave for the trenches assem- bled at a dinner in his honor, and some one proposed as a toast the health of the young man, his mother quickly rose and cried, "Non, non, — a la Victoire." We Americans should learn that same lesson. We may easily have need for it. [Since this was written we too have 51 MEDICAL RESEAKCH AND HUMAN WELFARE entered the war for Freedom and Humanity. May the same fervid patriotism be ours!] Well might Huxley say that Pastemr's dis- coveries alone would suffice to cover the vast German war indemnity in 1870. Think of the services of this "mere chemist." His first discoveries were in crystallography. He discovered the real cause of fermentation and^then of putrefaction. He laid the ghost of spontaneous generation. He built the foun- dations of Bacteriology. He proved the germ theory of disease. He saved for his beloved France the several industries of beer, of wine, of vinegar, of silk, of cattle, of poultry, of swine. Better than any one or all of these he showed how to abolish childbed fever and hydrophobia among his fellow-men. Fifteen victories and not one Waterloo! Where can we find a parallel? Sir Humphry Davy, when asked what was his greatest discovery, instantly replied, "Mi- chael Faraday." Had Pasteur been asked the same question he might well have replied, "Joseph Lister." The greatness of a nation is to be judged by the number of the great men it has produced. "Worship great men," said Pasteur to the students at the University of 52 ANTISEPTIC AND ASEPTIC SURGERY Edinburgh, all unconscious of the splendid egotism of his maxim. To-day in another university we gladly pay reverent homage to Pasteur and Lister, two of the world's greatest benefactors. ANTISEPTIC AND ASEPTIC SURGERY In his very first paper on "Antiseptic Sur- gery," in 1867, Lister proclaimed his large debt to Pasteur. Antiseptic surgery, as de- veloped in its basic principles by Lister, is the greatest "revolution" in the entire history of surgery, I need only give brief consideration to its triumphs, however, since it has been the theme of many others besides myself, not only in the surgical press, but in many magazines both lay and scientific, and even in newspapers so that all intelligent persons have a fairly exact knowledge of its immense value. Its inevitable successor was aseptic surgery. In fact it is a not uncommon lay criticism of some loitering surgeon who has not kept up with the progress of siu-gery, that he neglected this or that technic in the well-established ritual of antisepsis. 53 MEDICAL RESEARCH AND HUMAN WELFARE MODERN SURGERY I can give you only a faint idea of the bless- ings of modern surgery by a brief resume of a few of its many blessings. Wounds are either accidental, or, as in oper- ations, intentional. If we can care for] acci- dental wounds within the first twenty-four hours or less, we can almost certainly prevent infection by bacteria. This means that there will be Kttle or no inflammation nor any dis- charge of pus. That means immediate and almost painless healing. Thus, compound fractures, in which the bone protrudes through the skin, instead of killing two out of every three patients, as in my early professional life, at present have a mortality from infection of only one in several hundreds if treated early. If an ulcer of the stomach perforates and so allows the contents of the stomach to escape, this was formerly inevitably fatal, but now is not often fatal if treated early. Appendicitis has almost no mortality if treated early. Early — if possible immediate — care by a competent surgeon, in all such accidents, is the surgical "slogan." In fact that is true of almost all surgery. B4> MODERN SURGERY In my own early experience practically every wound, intentional or accidental, became an infected wound. During the Civil War I cannot recall a single wound that was not infected, and many a time in simimer I have seen them swarming with maggots — as large as chestnut worms — disgusting, but not especially dan- gerous guests. The mortality of wounds, and especially of gunshot woimds, was fearful. Blood-poisoning was frequent and its death- rate 97.4 per cent. Lockjaw often was seen and exacted a toll of over 89 per cent. Ordinary operations had a mortality of 15, 25 and 50 per cent or over. In consequence of the horrible pain in the days before anesthesia, and the terrible death-rate before antisepsis, no won- der that operations were as rare in those days as now they are frequent, for to-day Pain and Death are almost set at defiance. If the wound is intentional, as in removal of a timior or an amputation, we can almost always prevent infection, and if there is no ex- tensive imperative operative mutilation recov- ery is almost certain. Gallstones are removed, parts of the intestines are excised and the two open ends of the bowel are reunited, thus re- establishing the continuity of the bowel, tu- 55 MEDICAL RESEARCH AND HUMAN WELFARE mors of the liver are removed, stones in the kidney, or even one entire kidney, may be re- moved tdth wonderful success. Before the first hiunan kidney was ever removed by Simon in 1870, by experimental removal of one kidney he established the fact that animals could sur- vive with only one kidney. In 1887 I removed one kidney from a young woman on account of a gunshot wound. For two or three days it was doubtful whether the remaining kidney would be equal to the twofold load, then it quickly doubled its secretion, and she would have recovered had not another injury from the bullet, not discoverable at the operation, produced a fatal hemorrhage fourteen days later. The post mortem showed that the second kidney had increased twenty per cent in size during the fourteen days that she survived. When the necessity is laid upon her what can Mother Nature not do? When nerves are cut or shattered by a knife or a bullet, or when a bad fracture tears a nerve, we sew the nerve ends together, and if, again, we can operate early, we can generally remedy the injury and practically without danger. Thus the not very uncommon birth- palsies of an arm, and the wrist-drop from frac- 56 MODERN SURGERY ture of the arm-bone around which winds the nerve, supplying the muscles which bend the hand backward, are remediable. In one case I deliberately cut out two inches of the arm-bone because the ends of the nerve were so far apart that they could not be sewed together. The cut ends of the shortened bone were then wired together, the nerve ends met and were united, the woimd closed and speedy recovery took place. In a few weeks the patient had per- fectly normal wrist and hand movements. The mortality of amputations is now only ten to fifteen per cent, instead of fifty to sixty in every hundred, and only one patient in a hundred dies after an ovariotomy. We trans- plant portions of skin and pieces of bone as in an orchard we graft fruit trees. The horrible wounds of the face and jaws in the present war, which at first sight seem hope- less, by transplanting parts of ribs or portions of the shin-bone, and then patching and eking out the flesh and skin, are transformed in a few weeks into faces which will pass muster as to usefulness and comfort, though, if you will pardon the phrase, they would not often win a prize in a beauty show. The surgery of the head has been wholly 57 MEDICAL RESBABCH AND HUMAN WELFARE transformed in the last thirty years. Abscesses are opened, tumors or portions of the brain are removed from patients who before 1885 were always all allowed to die. Tic douloureux, that demon of pain, can now almost always be exorcised. The surgery of the chest has long lagged be- hind that of the rest of the body. When the chest is opened the corresponding lung col- lapses and the other lung may easily be un- able to do double work. If both sides are opened, death quickly follows unless means are at hand for instant artificial respiration. But within the last few years we have learned by experiments on animals that a tube can be inserted into the windpipe and by a bellows we can carry on artificial respiration with ether- lade& air until, when the operation is com- pleted, the chest wall can be closedWd normal respiration be reestablished. By this method we can now reach the lungs, the heart, and all the other organs in the chest and operate upon them at will. Portions of the lungs can be re- moved, abscesses opened, coins and other for- eign bodies which have been inhaled or swal- lowed, if they cannot be removed through the mouth or by operation in the neck, sometimes 58' MODERN SURGERY can be reached by this heroic and successful route. "The road to the heart is only a little over an inch in length in a direct line," says Professor F. S. Lee, "but it has taken surgery nearly twenty-four hundred years to travel it." In 1897 Rehn, of Frankfort-am-Main, published the first successful case of sewing up a wound of the heart. The need for such an operation is most frequently a stab wound. The opera- tion is a marvelous feat, for the sewing must be done while the heart lies in the surgeon's hand and keeps a& beating. Now over three hundred cases have been reported and nearly one half of them have recovered. Contrast this most imperfect list with what could be done in surgery when I graduated (1862). We then amputated limbs with a fear- ful mortality, removed a few external tumors, and buried a large percentage of our patients. One of 'the most common operations — for cancer of the breast — had a long and painful convalescence and a large mortality. Now it has a negligible death-rate and recovery follows in a week or two. Then we rarely operated for hernia and with little success. Now we cure practically all hernia cases and without any 59 MEDICAL RESEARCH AND HUMAN WELFARE mortality. A few other operations were done — ' and the list comes to an end. In a large and active hospital there were only about three im- portant operations in a month. To open the head, the chest, or the abdomen was then al- most equivalent to a death-warrant. Now you can do almost anything — provided you know how. All the operations I have mentioned, and many others, have been introduced during my professional life. Operations have now been made safe and, therefore, are frequent — ten, twenty, twenty-five a day in an active hospi- tal. Thousands, who a half-century ago were doomed to suffering and death, are restored to health and joyful life chiefly because of the researches of Pasteur, Lister, and their many successors. Sanitation has helped much, but never overlook the fact that nearly all modem sanitation, apart from engineering proper, is based upon Bacteriology, the lusty daughter of Experimental Research. SYPHILIS I know of no more striking instance of the value of experimental research and of Bacteri- 60 SYPHILIS ology than the very recent and impressive dis- coveries in syphilis. For four centuries this disease has ravaged the world. Tuberculosis and alcohol and syph- ilis may be called the greatest physical ene- mies of the human race. During all those four hundred years it had been studied clinically by many of the wisest and shrewdest surgeons. We had learned how to abate its evils to a con- siderable extent, but we knew not the cause nor any real cure. It never occurs naturally in animals. Many attempts had been made to in- oculate them so as to study the disease experi- mentally, but always without success. Sud- denly, in 1903, Metchnikoff, whose recent death is such a loss to science, succeeded in inoculating some higher apes. Since then we have learned how to inoculate other animals. Now mark the instant progress, the wonderful progress in our knowledge, directly due to animal experimentation. Two years later, in 1905, Schauduin and Hoffmann discovered the germ of the disease. The diagnosis of the disease could now be made with certainty, not only during its active exist- ence, but years and years later when the diag- nosis was generally inferential and uncertain. 61 MEDICAL RESEARCH AND HUMAN WELFARE In 1910, seven years later, Ehrlich discovered a cure. His recent death is another calamity. In these seven years more was learned as to the cause and cure of this terrible scourge than in four centuries of observation. This cure is the result of the most phenomenal patience and perseverance in the whole history of research. Ehrlich was led for certain reasons to use arsenical preparations. On inoculated animals he tested one preparation after another, but found this one too dangerous, that one ineffec- tive, others impracticable for one reason or another. But his mental and his chemical re- sources never failed. The lengthening list of preparations tried and tossed aside grew to one hundred, two hundred, four hundred, and six hundred without a single entirely satisfactory result. Imagine what six hundred complicated tests mean. What a splendid optimism, what a robust faith, must have pushed him on and ever on! Finally, the six hundred and sixth experiment succeeded! Improvements have fol- lowed a widening experience. We have learned that it is not an infallible cure. But for the vast majority of cases it is the very best and most reliable means we have and rarely fails. Think of the results to the whole human race ! 62 SYPHILIS Think, above all, what it means to the multi- tude of innocent victims; and thank God that such wonderful power for good has been vouch- safed to man! This discovery of the specific value of ar- senic to kill the germ of syphilis without harm- ing the patient is an instance of the specific action of a particular drug which I earnestly hope may foreshadow other discoveries of a similar character. We have a second specific remedy in quin- ine which kills the germ of malaria — an animal parasite in this case — without harming the patient. Mercury, when given in large doses, produces "salivation " with loss of the teeth — a harmful specific action. Still more remarkably local- ized is the well-known destructive action of phosphorus, from which so many workers in match factories suffered before the making of phosphorus matches was prohibited by law. Phosphorus not only selected the bony frame- work for its field of action, but limited its effects to one particular bone — the lower jaw. At the Rockefeller Institute, Dr. Walter A. Jacobs and his co-workers are now engaged in promising researches in an endeavor to find 63 MEDICAL RESEARCH AND HUMAN WELFARE chemical substances which will prove specifics to kill various bacteria without injury to the patient. If they discover any such remedies against the bacteria which cause infections such as abscesses, erysipelas, puerperal fever, etc., they will have opened a new era in medi- cine. Instead of external antiseptics to combat infection locally, these new internal synthetic antiseptics will attack the germs wherever they exist in the entire body. Some former world-wide plagues may be con- sidered here seriatim. SMALLPOX As I have limited myself principally to the researches during my professional lifetime, I shall only allude briefly to what has been done in smallpox since 1860. One of my own stud- ents, Dr. Victor G. Heiser, who was for a long time the eflScient Director of Health in the Philippines, has performed one enormous experiment on human beings that deserves notice. He has vaccinated over eight million people between 1905 and 1915 without a single death! In India during the year 1914 to 1915, 9,462,901 people were vaccinated, again with- 64 SMALLPOX out a single death! When one remembers the uncleanly habits of the masses vaccinated, and that every vaccination is a small surgical wound, and unless properly protected is liable to infection with all its serious danger of blood-poisoning, these two series of vaccina- tions were marvelously successful. Moreover, Heiser has told me the striking story of the results in over one million vaccina- tions in and around Manila. Before his vac- cinations there were every year about six thousand deaths from smallpox. In the twelve months following the completion of his vaccina- tions in the same area, there was not one single death from smallpox! Could any person mth common sense ask for better evidence of the pro- tective value of vaccination? By a curious coincidence another disastrous, unauthorized experiment was made in the Philippines which is a striking contrast to that of Dr. Heiser. On one of the small isolated islands, with a population of two thousand, an old woman, instead of protective vaccination, inoculated a number of persons with the small- pox pus from a human case. An epidemic of smallpox immediately broke out, resulting in one thousand cases, half the entire population, 65 MEDICAL RESEARCH AND HUMAN WELFARE four hundred of whom died. As quickly as the facts were learned by Dr. Heiser, vaccinators were sent immediately to the island. Eight hun- dred of the remaining one thousand unvaccin- ated inhabitants were immediately vaccinated. There were no cases and no deaths from small- pox in these eight hundred who had been vaccinated. The other two hundred ignorant, superstitious people fled to the mountains and nothing is known as to their fate. The epidemic of 1885 in Montreal teaches a similar lesson. A Pullman porter reached Montreal as his attack of smallpox was just be- ginning. That one case resulted in 3164 deaths and probably disfigured or bhnded from ten thousand to twelve thousand persons, to say nothing of the expenses" attendant on the illness of so many persons and the great pecuniary loss to the merchants of that city. During the Civil War and later once in Phila- delphia, I have passed through three epidemics of smallpox, and I do not hesitate to say that it is the most loathsome disease I know and its results in those who recover are the most repulsive and pitiful. One objection against vaccination has been urged that tetanus is sometimes produced by 66 CHOLERA an impure vaccine. This statement is entirely erroneous. Whenever tetanus has followed vaccination (as it may follow any wound), the United States Public Health Service has inves- tigated the cases and "in no instance could it be shown that the disease was attributable to the virus." CHOLERA I need do no more than refer to this pesti- lence, for that we have got the whip-hand of it is a matter of common knowledge. But how have we done so? Largely sanitation — a clean water-supply and a vigilant prompt seg- regation of every case. But the imperative need of a clean water-supply had been disclosed and enforced by the discovery of the microbe of cholera and that this microbe was the water- borne means of spreading the epidemic. Medi- cal Research has also taught us how to cope with such an epidemic. The causes of cholera, plague, malaria, and tuberculosis have all been discovered during my lifetime. We have cut down their mortality enormously and our future success will be even greater. 67 MEDICAL RESEARCH AND HUMAN WELFARE the rat-flea carries the infection from the rat to man. Hence the plain lesson. What Carthage was to Cato the rat is to the modern sanitarian. Delendus est. In the European quarter of Bom- bay all the rats were destroyed; in the native quarter the destruction of animal life was ta- boo, for might not a human soul be enshrined there in one of its many transmigrations? You may recall what Rupert Blue, then a subordinate of the Public Health Service, now its able Surgeon-General, did in San Francisco. Besides looking after the patients themselves, he trapped and poisoned every rat, and rat- proofed their possible places of refuge. For eight years there has not been a case of plague in San Francisco. The last infected rat was found seven years ago. In the New Orleans outbreak of 1915 nearly five hundred thousand rats were caught; two hundred and sirty-five infected rats were found in nearly three hundred thousand which were examined, and the epidemic was arrested. The germ of the plague, the "bacillus pestis," was discovered in 1894 by Yersin and Kitasato and our immunity from epidemics is due solely to Bacteriology. Haffkine discovered, also by Bacteriology, a vaccine which reduced the case 70 YELLOW FEVER mortality from 60 per cent to 24 per cent. Yer- sin, of the Pasteur Institute, has apparently im- proved upon this. YELLOW FEVER Another veritable romance of medicine of surpassing interest is the discovery of the means of the total prevention of yellow fever. The cause of smallpox and the cause of yel- low fever have so far eluded the most intense and unintermittent search by many astute and persevering men. But that they will be found I have not the slightest doubt. It is only a question of time. But in both of these terrible diseases we have found the means for their prevention and, if medical advice were univer- sally followed, for their total eradication. In 1847 Mott, of Alabama, advanced the theory that insects may be carriers of disease, and in 1876 Dowell, of Galveston, called atten- tion to the similarity of the natural laws gov- erning the gnat and the mosquito and yellow fever, but without result. In 1881 Carlos Fin- lay, a graduate of the Jefferson Medical College of Philadelphia, declared that yellow fever was 71 MEDICAL RESEARCH AND HUMAN WELFARE transmitted from man to man by the stegomeia mosquito, but his words fell on deaf ears. In 1898 the careful observations of Henry R. Carter, of the Marine Hospital Service (now the Public Health Service), gave important support to the mosquito theory. Finally the American Commission — how proud I am that they were my fellow-countrymen! — in 1900 positively proved that Finlay was right. The problem was most complex. There are about four hundred varieties of mosquitoes, yet the Commission were able to identify the two which carried, one, the yeUow-fever germ, the other the malaria germ. They discovered that only the female is the biter. They found that the female mosquito must bite a yellow-fever patient during the first three days of the fever, and that then it requires twelve days for the germ — still unknown — to develop in the body of the mosquito^ There was still much in- credulity ; many still believed that yeUow fever was carried by clothing, bedding, etc., — the so-called "fomites." To disprove this mode of infection the doctors slept for many nights in the soiled clothing in which yellow-fever pa- tients had just died, they tried every repulsive method by inoculation, even to swallowing the 73 YELLOW FEVER black vomit, but all in vain. Not one of them contracted the fever. Then came the supreme test. No animal can be inoculated with yellow fever. The only pos- sibility of the test was in human beings who would allow themselves to be bitten by mos- quitoes known to be infected. Who were the very first to oflfer themselves? The doctors of the Commission themselves. Agramonte barely escaped with his life; Lazear lost his young, promising life for the sake of Humanity — a sacrifice as noble as any young warrior hero in a forlorn hope. To-day we owe oiu- immunity from yellow fever to these heroes of medicine. The last case of yellow fever contracted on the Isthmus of Panama was in 1905 — nearly twelve years ago ! Never agaia can there be a great epidemic of yellow fever in the United States. Those of you who have read Weir Mitchell's "Red City" will appreciate what a wonderful triumph this is for Medical Research. The YeUow-Fever Commission of the Rocke- feller Foundation has just returned from a care- ful investigation of the various foci of iafection in South America. Guayaquil is the principal source of infection, with one or two minor possi- 73 MEDICAL RESEARCH A?JD HUMAN WELFARE ble foci. Yellow fever is reported to exist in Mexico and on the west coast of Africa. It be- hooves us immediately to bestir ourselves, for otherwise the opening of the Panama Canal — a veritable Pandora's box — may easily result in serious epidemics of yellow fever in countries in which it is as yet unknown. A systematic campaign against the mosquito and for the adoption of the sanitary measures found to be so successful on the Isthmus may enable us to banish yeUow fever from the whole world. MALARIA This is a foe almost as deadly and far more widely spread than yellow fever. Living in the temperate zone we do not appreciate how deadly it is in tropical, and even semi-tropical, countries. In 1908, in India, malaria in a malig- nant form burst upon the province of the Punjab and killed nearly three hundred thousand per- sons in two months. The decadence of Greece has been attributed to the introduction of in- fected anopheles mosquitoes by immigrants in the fifth century B.C. After a most careful investigation the Inter- 74 MALARIA national Health Commission of the Rocke- feller Foundation describes malaria as "a dis- ease which, taking the world as a whole, is probably the heaviest handicap on the welfare and economic eflficiency of the human race." The value of protection from the malarial mosquito is well shown by the recent experience of the United States man-of-war Des Moines in the harbor of Tampico. When the ship cleared for action all the screens had to be removed. Immediately, out of a crew of 293, 219 fell ill of malaria. "No mosquitoes, no yellow fever" "No mosquitoes, no malaria" are axioms of tropical sanitation. The International Health Commission, in co- operation with the United States Public Health Service, is making three remarkable experi- ments to discover the best means of dealing with this tremendous problem. In each case small malarious communities were selected so that the cases could easily be identified. In each town they are testing one, and only one, method. The first is solely by abolishing the breeding- places and therefore the number of mosquitoes without expensive drainage; the second is by only screening the houses; and the third by 75 MEDICAL RESEARCH AND HUMAN WELFARE using quinine as a preventive without any other measures. The result of the first method is very striking, and, as Mr. Wickliffe Rose, the Director of the Health Commission, writes me, is "no longer an experiment, but a very satisfactory demon- stration." In a town with a population of 2029 persons the number of cases of malaria month by month during 1915 began in January with 40, by June reached 125, by August 350, and by October 600 cases. By December it had rapidly fallen to 100 cases. In January, 1916, there were 35 cases, the maximum of only 120 cases by May and by December had fallen to four cases. The total number of cases in 1915 was 2500. The simple, inexpensive measures adopted cut this number to 743 in 1916, and in succeeding years will undoubtedly show even better results. (See Chart I.) While not eradicated, malaria in that town is no longer a serious menace. Screening and quinine in addition will certainly much further reduce the number of cases of malaria in the future and even beget a hope of the ultimate extinction of this vast plague. A French army surgeon, Laveran, in Algeria in 1880, discovered the cause of malaria, an 76 MONTHLY DISTRIBUTION OF CALLS FOR MALARIA AT CROSSETT. ARK. Pop. 2029 Office, Hospitat, and Residence. - - ■ = - .. - ■ .-■ « ■ • - , 9 ■ - - ^ . . . „ .. _ _ . l_ _ _ _ _ : : ~ : -' : : : : : : : :' - ! ;: ;a ! II : : - ~ I : - - - - s - ^ - - - - ■ ■ , 1 1 j j - - " - - . E p ■ ■ ■ ■ - - - - " 1 10 in 2 2 2 5 at s 32 § s ss ^CSJ 2g crj ■^ g S§ >§ 8 gg C 1 1 C ? = 3 3 - 1 DC Q ^ s a ^ £ £ .' -■ 5z:|q __ S § S 1 s o In •* ^ m 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 » jiaquiajx: #- :: : :: ::::::: :^^" " ■ : : ::::#: L ' \^ir- 11 ] 1/ ::::::::::: :::::::::::::::::: " " ^1 ------- -- - - ^■ji ' ^ ' Willi' .1: " , 11 I "I — """ :: 3; . ; : : S^ L : : " " : ' s : r " ^ -'- - ^ - rV 1 1 g 8 8° M -a " S a MALARIA animal parasite, which, like the unknown germ of yellow fever, has two phases of life, one in the mosquito, the other in the patient. (Plate II, Fig. 1.) No longer is "a touch of malaria "allow- able as a cloak for our ignorance of the cause of any illness. Now, if the parasite is found in your red blood corpuscles you have malaria; if they are not found, you have not. Ross in malaria-ridden Secunderabad, after experimenting in vain on a long series of mos- quitoes, bred for the purpose in his laboratory, on August 15, 1897, had just eight left. Six gave no results; the seventh seemed to point the way; in the eighth and last he reached his goal. "These two observations solved the malaria problem." The parasites were found, not as had been supposed in the stomach, but in the salivary glands of the mosquito. The exact route of infection of this disease which annually slays its millions of human beings was now revealed. "Never in our dreams," said Ross, "had we imagined so wonderful a tale as this." A single mosquito can infect several per- sons, and in view of the number of these pests it is easily seen how whole communities may be attacked. These experiments again were made upon unselfish doctors. 77 MEDICAL RESEAHCH AND HUMAN WELFARE It is a strange fact that the malarial and the yellow-fever mosquitoes, and the goats infected with the germs of Malta fever (vide infra), seem to be in no way deleteriously affected by the germs they harbor. What has been the result on the Isthmus from the work of General Gorgas? Before this, the greatest experiment in sanitation ever tried in the world, among 45,000 employes, — more than an army corps, — the mortality while the French were digging the Canal was 240 per 1000. In 1913, among 56,000, an in- crease of 25 per cent in numbers, the mortality was 8.35 per cent per 1000, almost one thirtieth of the former rate. General Funston had 24,000 men at Vera Cruz in 1914. Although Vera Cruz was an ill-kept tropical city in which smallpox and typhoid fever, and an epidemic of cerebro- spinal meningitis were rife, yet not a single case of any of these diseases was reported in our troops. Our huge and splendidly successful experi- ment on the Isthmus has shown that the white man can live and work in the tropics, and yet maintain his health. This achievement is of far greater importance as to the Welfare 78 MALARIA of the Human Race than even the splendid en- gineering success of constructing the Canal itself. The work of Dr. Heiser and his staff in the Philippines has been quite on a par as to use- fulness with that done on the Isthmus by General Gorgas and his collaborators. It is not as widely known as it ought to be, and it is, therefore, with pleasure as a friend and pride as one of his teachers that I call atten- tion to it in a very few words. The number of deaths has been lowered by about 75,000 per annum. The death-rate in Manila has been re- duced from 43 per 1000 to 23 per 1000, not a bad showing for a large city in the tropics. Smallpox, as abeady indicated, has been al- most conquered. Bubonic plague has been extirpated and cholera controlled. Heiser has put in operation a city sanitary code that is said to be more complete than that in use in any other large city in the world. In several countries his organization of the Health Department in the Philippines has served as a model on which they have built — a recent compliment being a similar action by the State of Massachusetts. 79 MEDICAL KESEAECH AND HUMAN WELFARE HOOKWORM The name describes the parasite. (Plate I, Fig. 3.) It lives in the human intestines. It has been known for eighty years, but only in 1898 did Loos discover the portal of entry. It penetrates the skin of the hands, feet, etc., and in time reaches the intestine. In the news- papers it is called the "bug of laziness." But this is a serious misnomer. The victims of the malady are not "lazy." Their development, both physical and mental, has been retarded. They are indolent from incapacity, not from unwillingness. Dr. E. K. Strong, of the Rocke- feller Foundation, has shown that even com- pletely cured children gained mentally only sixty per cent as much as normal children; i.e., that they had less than two thirds of the men- tal capacity of normal children. Moreover, the longer they had suffered from the disease the greater was their mental loss and the more slowly did they progress toward the normal. If the disease had lasted a considerable time it was doubtful whether they ever could reach a normal mental development. Physically its victims are relatively several pounds lighter in weight and it may be even 80 HOOKWORM some inches under the normal height for chil- dren of the same age. The moment they were cured immediate and rapid increase in weight was observed. The story of the hookworm campaign by the Rockefeller Foimdation is a story of wonder- ful interest and will in time bear wonderful fruit. In 1915 this campaign covered ten of oiu" Southern States and eighteen foreign countries. Hookworm disease extends over a belt nearly four thousand miles wide, girdling the whole earth from 36° north latitude to 30° south latitude. It includes the United States south of San Francisco and Richmond, all of Central America and the West Indies, South America as far south as Buenos Aires and iSan- tiago di Chile, all of Africa save Cape Colony, all of Asia Minor, Persia, India, Southern China, Korea, and Japan, the Philippines, all of Australia and most of the Pacific groups of islands. This belt includes more than half of all the inhabitants of the entire globe. You see, therefore, the hugeness of the prob- lem of its extermination, but I firmly believe that the attempt will succeed. Careful micro- scopic examinations of the excreta of almost a million and a half of people all over the world 81 MEDICAL RESEARCH AND HUMAN WELFARE showed the minimum iofection of over twenty- seven persons out of every hundred, and the maximum in Ceylon, where on certain planta- tions only four persons out of every himdred were free. Recently in the East he even found some places where practically every person was infected. The worm differs wholly from the familiar infectious bacteria. It does not multiply in the human intestine. Each individual worm ex- pelled by purgatives has entered the body by penetrating the skin from without and then has literally "wormed" its way to the intestine. As many as six thousand have been expelled from a single patient. i Thymol and oil of chenopodium are eflBcient remedies. In Porto Rico three hundred thous- and patients were cured and their efficiency at once increased by twenty to thirty per cent. i The way in which the disease is spread is not an agreeable study, but it is one that must be told plainly or the seriousness of the menace to ourselves in our Southern States and all over the world in the wide equatorial belt will not be appreciated. Oiu- smug satisfaction with our splendidly HOOKWORM elaborate and costly sanitary plumbing re- ceives a terrible jolt when we learn that in the twentieth century, in a highly civilized country as we profess to be, a detailed examination of 287,600 farmhouses in eleven of our Southern States disclosed the fact that 142,230 had no cesspools of any kind whatever. Of these 287,600 farmhouses only six tenths of one per cent! — i.e., 1726 — had satisfactory arrange- ments to prevent soil infection by the dejecta. The hookworms in this infected soil lay in wait for every barefoot person who walked over it. The means of the entire extirpation of this disease are theoretically very simple and very certain: (1) Cure those now infected by the treatment mentioned; (2) make everybody wear shoes; and (3) compel the introduction of effi- cient cheap latrines of such a character as to prevent further soil infection. All this is very simple on paper, but when you come to put it in practice it soon discloses itself as a problem not so much of legal com- pulsion as a huge problem of education of six to seven hundred million people of all degrees of civilization, the majority, perhaps, of low, often the very lowest, intelligence, speaking 83 MEDICAL RESEARCH AND HUMAN WELFARE hundreds of different languages and under many rulers in the great equatorial "hook- worm belt." But that in time it will succeed, especially as country after country sees convincing proofs of the value of those measures, I have a firm behef. I am proud that such beneficent, far-reach- ing plans have been laid in my own dear country and that more than one of my own students have had a hand in the work. TUBERCULOSIS Tuberculosis — the "Great White Plague," or " Captain of the Hosts of Death," as it has been truly and picturesquely called — in 1914 killed 96,000 persons in the "registra- tion area" of the United States. As this covers only two thirds of our population it is a fair inference that in 1914 it destroyed 144,000 lives in the United States. What a huge loss of life; what a huge loss of effective power; what a huge expense to pay the bills incurred in their care and their burial; and finally, what a huge wave of suffering in its victims and of sorrow in their families and 84 TUBERCULOSIS friends! And yet in 1914 its ravages had been greatly curtailed from what it was fifty years ago. Not only have its ravages been curtailed, but the mental attitude of the pubUc and of the patients themselves has been changed. When I started in medicine, once that a patient was pronounced "consumptive," all hope was gone, he was a doomed man, the only question was, "How short will his life be?" Moreover, his descendants were believed to be in the shadow of the same disease. In 1866 I taught my classes that tuberculosis was positively con- tagious, for ViUemin a year earher had discov- ered and proved this by injecting tuberculous tissue and sputum into rabbits. That was an immensely important discovery and occurred even before we knew the cause, for Bacteriol- ogy did not then exist. Sixteen years later, after Pasteur and Lister had established the truths of Bacteriology, came the momentous, the all-important, discovery of its cause. I well remember that Monday morning in 1882 when the editorial staff of the "Medical News" gath- ered to decide on the editorials for the next Saturday's issue. A cable had just been re- ceived announcing Koch's discovery of the 85 MEDICAL RESEARCH AND HUMAN WELFARE tubercle bacillus. The late Roberts Bartholow wrote the editorial announcing the epochal discovery. Our sanitary precautions are practically all based on that happy discovery. We learned then how and why the disease spreads. Cough- ing, laughing, sneezing, spitting by tubercu- lous patients, eject the tubercle bacilli into the air, on to the pavement or the floor or the clothing, there to dry, to become pulverized, and to be inhaled by the well. Hence the danger in the use of common utensils, such as drinking-cups. When it was proved that fresh air and sunlight were active enemies of the tubercle bacillus, the fresh-air cure, including sleeping out-of-doors instead of in closed rooms, became the vogue. Then we learned how to diagnose tuberculosis by the micro- scopic examination of the sputum or the ex- creta for tubercle bacilli far earUer than by its physical signs; i.e., by percussing and auscultating the chest. The microscope was the sentry which gave the alarm, and called at once for the mobilization of our sanitary and therapeutic forces to combat the invading bacillus. Then we learned that scrofula, that Pott's disease of the spine resulting in a hunch- 86 TUBERCULOSIS back, that the so-called "cold abscess" which was so chronic and entirely free from heat, that many diseases of bones and joints, were aU different forms of tuberculosis. StiU later have come the "tuberculin" test by which we safe- guard ourselves and especially our children from tuberculous milk, and several other tech- nical tests by which we can detect tuberculosis even in its very beginning and in latent and otherwise undetectable stages. Our errors were corrected, our treatment be- came simplified and scientific instead of empiri- cal. Then the death-rate began to fall. In Boston, for example, in the twenty years before Koch's discovery (1882) the death-rate from "tuberculosis" was 420 per 100,000. In fact it was much higher than 420, for "tuberculosis" then included scarcely any cases except tuber- culosis of the lungs. Twenty years later the death-rate had fallen to one half (210), and since then it has fallen to 180 per 100,000 and below. All over the world, where its Bacteri- ology and the consequent necessary sanitary measures are known and practiced, the death- rate has fallen nearly or quite to one half, and is steadily falling still lower. If only we could completely control every 87 MEDICAL EESEARCH AND HUMAN WELFARE case, tuberculosis could be extinguished in twenty years. The keystone of this Triumphal Arch of Progress is the discovery of the tubercle bacillus only thirty-five years ago. And what does this veritable Kttle "beast" look like in the microscope? It has to be stained in order to see it well and then each bacillus looks much like one of the short colored threads in our bank- notes. It is as motionless as they — but it is a deadly enemy. (Plate I, Fig. 3.) CANCEB There seems to be little doubt that cancer is growing in frequency as a cause of death and always with terrible suffering. It is, there- fore, a pressing question. No other enemy has been more persistently assaulted in the last twenty-five years — not even tuberculosis. It has been attacked by the cUnician, the pathologist, the microscopist, the comparative pathologist, by all the resources of experimental research, by the X-rays and radium, by special Institutes and Endowments in Europe and America. We have stormed the outlying forts, but this grim Verdun of disease has not yet capitulated. 88 CANCER For experimental research mice are chosen on account of their very short lives and ready susceptibility to infection. In a short time many generations can be bred and tested. For man, only three or four generation^ could be studied in an entire century, and meantime the student himself would have died with his work hardly more than begun. Moreover, our stud- ies would be limited to the cases occurring naturally. No experimental work could be done on man. I should add that these cancerous mice which I have often watched and held in my hand, even when bearing a cancer nearly as large as themselves, were as alert and Uvely as usual and showed not the sUghtest evidence of any pain or even discomfort. In mice by appropriate matings we can now produce at will a race of descendants with a cancer rate as high as sixty to seventy per cent or one as low as nine per cent. The explanation is not easy. It may be that there is a disturb- ance in the normal balanced development of the multitude of differentiated cells of the various tissues arising from the unicellular ovum. In cancer this normal balance is lost. Instead of a development predetermined for MEDICAL RESEARCH AND HUMAN WELFARE each organ the cells of cancer run riot. Instead of performing a useful function as all normal cells do, the cancer cells grow without serving any useful purpose in the body. What factor produces this difference we do not yet know- On the contrary, as is strongly suggested by the remarkable work in cancer in plants by Dr. Edwin F. Smith, of Washington (vide infra), it may be due to either an unknown, probably filterable, and, therefore, excessively small, almost imdiscoverable bacterium or to an animal parasite. The cancer problem is one not limited to man. It is a large problem of general biology for it attacks not only man, but the lower animals, birds, fishes, and even plants. Smith, as we shall see later, can produce what seems to be really cancer in plants at will by a hypo- dermic injection of his bacterium tumefadens. But mark my word — the cancer problem will be solved by science. That will be, indeed, a happy day for us surgeons when we have found the cause. We shall then be hot on the trail of the cure and that, too, without operation as we sincerely hope. Meantime we know of only one real cure — the knife. Radium and X-rays and high fre- 90 CANCER quency currents are useful in a small percent- age of cases — but too often they delay the radical remedy tiU it is too late, and so, in fact, increase the mortality. But remember that the knife is only depend- able in the early, and if possible the earliest stages. If every man and especially every woman were to submit to the knife — now used without any practical danger to life — one per cent or less in skillful hands — the moment that a lump was found, the deaths from cancer would be only twenty-five per cent, or twenty per cent, or even less. Thirty years ago I would have told you that I had never cured a single case, but had only postponed the final event. The very few cases of permanent escape I be- lieve were cases of mistaken diagnosis. Now, you see thai this somber picture has been painted out, and hope has replaced despair. Some of my cases are still alive and well after ten, twenty, or even twenty-five years. Remember, too, that persistent moles and warts, especially the dark-colored ones, are always a menace to life. Many of them, like the Lassen Volcano in California, long quies- cent and seemingly innocent, suddenly burst into rapid growth, and then, even though ex- 91 MEDICAL RESEAECH AND HUMAN WELFARE tirpated at once, are often fatal. They ought to be removed before they begin to grow. Any lump, anywhere, which is not normal, with few exceptions demands immediate re- moval. It cannot be too strongly stated that in its early stages cancer is always a local dis- ease, and in very many cases is permanently curable. In its later stages death is assured in a rapidly increasing percentage. Even though Medical Research has not yet found its cause, it has proved its curability, in the early stages. DIPHTHERIA I have a fierce hatred of diphtheria. When I was twelve it strangled to death a younger playmate brother, my parents' "Benjamin." When I was thirty it slew a sweet little niece and desolated another brother's home. It almost killed my dear friend Weir Mitchell. It robbed him of the wife of his youth and a daughter of his later life. For nearly thirty years during an active surgical life, I met it again and again, Uterally in a life-and-death struggle for the life of little children, and again and again it has defeated my best efforts to save them. I had the small comfort that at DIPHTHERIA least they were not choked to death, but fell victims to the somewhat less cruel poison of the disease. No wonder that I hate it ! How often in those dark days have I stood, as it were, knife in hand, by the bedside of a gasping child, until at last the worn and sob- bing parents could overcome their horror and permit me to try the last desperate surgical means of relief — a tracheotomy; i.e., making an opening in the wind pipe to prevent slow sujffocation — but alas, so often fruitless. Now, thank God, it is many years since I have had to resort to a tracheotomy, for the blessed diphtheria antitoxin has practically abolished tracheotomy in diphtheria. Note these words "has practically abolished tracheotomy in diph- theria. Death still claims some victims, but its harvest is scanty and is steadily lessening, as I shall show. In 1883 Klebs and, later, Loeffler discovered the germ of diphtheria. (Plate I, Fig. 4.) In 1890 Behring in Germany and ICitasato in Japan, by inoculating goats first with very small and then with gradually increasing doses of the toxin of diphtheria, as Pasteur had done in anthrax and hydrophobia, found that these animals could finally withstand the strongest 93 MEDICAL RESEARCH AND HUMAN WELFARE doses, which would have been quickly fatal at the beginning. These animals had become inunune, and, what is better still, the antitoxin thus developed in their blood, if injected into a healthy animal, such as a horse, made that animal immune by producing in its blood the antitoxin. When the blood serum from such an immune horse is injected into humans they are made immune, not by the blood serum of the horse itself, for only a small quantity is injected, but because this small quantity induces in the blood of the humans so inoculated the produc- tion of a new antitoxin of their own; i.e., each patient is enabled to manufacture his own anti- toxin. Not only is this antitoxin a prophylactic, i.e. preventive, but it is curative; and curative pre- cisely in proportion to its early use, because the earlier it is used, the more quickly does the blood of the sick child produce its own defens- ive antitoxin. To the surgeon it has brought untold relief as well as to the patient and family. Tracheo- tomy for diphtheria, as typified by my own personal experience, I repeat, has practically disappeared. Such frightful cases as were fre- quent before 1895 have ceased to be. No one, 94 DIPHTHERIA save an old surgeon like myself who has gone through many such harrowing, heart-breaking experiences, can appreciate the joy of our present deliverance. Could there be a better contribution to Human Welfare? Nature never tired of her thousands of cruel experiments on children. The doctors did not experiment on children, but by quiet research in the laboratory, surrounded by a few rabbits and guinea pigs, worked out the whole anti- toxin treatment. When certain of the results on animals, then they used it in human pa- tients, and behold the splendid results! With what intense satisfaction I show you these splendid results only those who have traversed the thorny path of experience like my own can fully appreciate. The antitoxin was first used in 1895 and has steadily grown in favor. Now, the physician who does not use it and use it speedily is guilty of criminal negligence. I show you here four diphtheria tables and charts which will repay study. First, the mortality in cases in which the antitoxin was used on the first day, when not one of 218 cases died; then a rapidly ascending percentage of deaths day by day for the second, m MEDICAL RESEARCH AND HUMAN WELFARE third, and fourth day. After the fifth day there was a slight decrease for the more susceptible patients had already been slain. The danger of delay is then strongly emphasized. Table I. Dephtheeia Death-Rate Accoedikg to Day on which the Antitoxin was used ^ Day Cases 1 218 2 1163 4.69 8 880 12.50 4 598 16.40 5 851 14.24 After 5th day 694 14.15 The second table shows the death-rate per 100,000 of population in New York City at ten years' intervals from 1874 to 1914. Note the sudden and gratifying drop after the antitoxin was first used in 1895. TABiiE n. Deaths in New Yoek City pbom DiPBTHEBIA 1874 219 per 100,000 inhabitants 1884 136 " 1894 158 " 1895 Antitoxin Treatment Begun 1904 67 per 100,000 inhabitants 1914 29.5 " " « 96 I I I O CO Ka ^^ "-it I^ I iliiii MEDICAL RESEAKCH AND HUMAN WELFARE The charts I owe to the courtesy of Mr. Frederick S. Crum, Assistant Statistician of the Prudential Insurance Company, in New- ark, New Jersey, not, be it observed, a medical man, with a theory to prove, but a man of cold but eloquent figures. Chart No. II shows, to the left, the mor- tality rates per 100,000 of population in fifteen American cities, before the introduction of the antitoxin for diphtheria, and to the right the mortality rates after its introduction (1895). The black lines are drawn to a scale of 25, 50, etc. The line of 125 deaths per 100,000 in- habitants is passed by only three cities, Brook- lyn 132.3, New York 130.1, and Denver 128.5. The lowest rate is 51.5 in New Orleans. Contrast with this the rates for the same cities after the introduction of the antitoxin. On a similar scale Chicago leads with 38.1 in place of 117, while Washington has fallen from 80.1 to 7.1 per 100,000. Every city shows a wonderful fall. Chart No. HI shows the death-rate in twenty countries of the world, before (left hand) and after (right hand) 1895. Before the use of the antitoxin Serbia leads with 411.9 deaths per 100,000 of population, then follows i-rlBlHiiilii^ P4 H 1:1 -^ if Ji.li||i|||gSII§S|5|a MEDICAL RESEARCH AND HTJMAN WELFARE Prussia with 143.1, Denmark with 134, Austria with 119.3, and the United States with 120.1. Now, look on the right-hand side. The antitoxin has caused a most extraordinary fall in every country. Serbia has fallen to 40.1, Prussia to 22.6, Deimiark to 7.9, Austria to 25.9, and the United States to 27.1 instead of 120.1. The statistics of fifteen American cities and of twenty countries of the world thus present overwhelming evidence of the blessing the anti- toxin has brought to all mankind. A conspir- acy to "doctor" the statistics and mislead the world is an impossibility. Even if Serbia be discarded, the rest of the tables are suflficiently eloquent. CEREBRO- SPINAL MENINGITIS Cerebro-spinal meningitis breaks out occa- sionally into widely spread epidemics with a mortality of seventy-five per cent or more. Many erroneous diagnoses are made and cases are officially reported to city boards of health as cerebro-spinal meningitis which a more careful and thorough investigation shows not to have been such. The only positively ac- curate diagnosis is by "lumbar puncture." 100 CEREBRO-SPINAL MENINGITIS This method was introduced ia 1891 by Quincke, of Kiel. The long, slender needle of a hypodermic syringe is thrust within the sheath of the spinal cord in the small of the back — the lumbar region — and a small quantity of the cerebro-spinal fluid is with- drawn. By its examination the diagnosis is made certain. But as in so many other cases Medical Re- search does not stop with finding out the cause and making a diagnosis. It rapidly pushes on to the further discovery of a remedy. That is the reason we are always so desperately anxious to find the cause oi cancer. When that is found we shall be very near to its ciu*e, or better still to its prevention. The remedy for cerebro-spinal meningitis is a serum elaborated by Flexner at the Rocke- feller Institute. This curative senma is injected into the sheath of the spinal cord through the same needle by which the cerebro-spinal fluid is withdrawn for diagnosis and before remov- ing the needle. A single puncture, therefore, answers both for diagnosis and treatment, "And what," you ask with intense interest,' — "what is the result of such a means of sure diagnosis and of the use of such aserum? " With 101 MEDICAL KESEAKCH AND HUMAN WELFARE pride and joy I reply that the mortality has been cut down from seventy-five to at least twenty-five per cent in most cases, and in some instances to as low as seven per cent. More- over, apparently an efficient disinfectant for " carriers " of this disease has probably been found. Do not such results accredit Medical Re- search with a notable contribution to Human Welfare? TYPHOID FEVER Typhoid fever has been one of the historic scourges of armies all over the world. It is a constant cause of many deaths in our civil population, especially in our large cities. The autumnal harvest of deaths from typhoid has been so common as scarcely to cause remark, until of late, when we have learned the lesson of our municipal culpability. Since Bacteriology revealed the cause and Medical Research discovered the antidote, we have practically conquered typhoid fever in the army and navy. Were the civil population to follow the example of the army and navy there would be few cases of this justly dreaded disease. 102 TYPHOID FEVER The bacillus of typhoid was discovered by Eberth in 1880. It is so small that it takes 40,000,000 of them to weigh a single grain. (Plate I, Fig. 5.) Like the discovery of the tubercle bacillus two years later by Koch, this was an epoch-making discovery. Practically aU of our sanitary precautions, and now our preventive means by vaccination with the anti-typhoid serum, start from the discovery of the bacillus of typhoid. In the Civil War there were 79,462 cases and 29,336 deaths, a death-rate of thirty-seven per cent — a horrible toll of life! The total number of deaths in the army of the United States in the Civil War was 303,504. Typhoid alone was responsible for nearly one tenth of all deaths! In the Boer War there were 58,000 cases and 8000 deaths, a death-rate of fom-teen per cent. Of the total deaths in that war 22,000 in num- ber from all causes, typhoid caused over one third! In the Spanish-American War there were 20,738 cases — nearly one fifth of the entire army — and 1580 deaths. Eighty-six per cent of the entire mortality in that short war were due to typhoid! 103 MEDICAL RESEARCH AND HUMAN WELFARE A beautiful experiment by Professor Coplin, one of my colleagues at the Jefferson, well shows one of the principal means of spreading the disease in armies. He made a fly walk across a plate of gelatin on which was growing a pure culture of the typhoid bacillus. Then he caused the same fly immediately to walk over the surface of a plate of sterile gelatin. This latter plate was then placed in an oven at a suitable temperature. Wherever the contam- inated feet of the fly had touched the sterile gelatin, there a colony of typhoid bacilli sprang up. The footprints of the fly were as evident as the footprints of a horse on a newly smoothed dirt road. (Plate II, Pig. 2.) Any fly which has walked over the infected excreta of a typhoid patient and then walks over the sol- dier's or our own food carries the infection in like manner. The water-supply, the milk-sup- ply, the fly, and handling food with unwashed hands (how scientific is the Mosaic code in these respects!) — these are the main sources of infection. Many severe epidemics have been traced to an infected milk-supply — originating, it may be, from a single case of typhoid on the farm or in the dairy. 101 Fig. 1. Different Phases of Development of the Malaria Parasite Fig. 2. Typhoid Fly Tracks Note the left-hand interrupted line (n) and the almost parallel dotted line to the ri?ht of a. The 6rst, a, was made by the left wing, the other by the right feet of the fly (sec text). Each of these lines represents a row of colonies of typhoid bacilli growing on sterile gelatin infected by a typhoid fly which had once walked over a culture of typhoid bacilli and then once over the sterile gelatin. PLATE II TYPHOID FEVER I will only cite one instance of an infected water-supply caused by one single patient. The town of Plymouth, Pennsylvania, was supplied with water from a near-by lake. On a hillside bordering on the lake there occurred in 1885 one case of typhoid fever. This patient's dejecta was thrown out on the snow. When the snow melted in the spring the water ran into the lake. This carelessness in one family caused an epidemic of over twelve hundred cases of typhoid and over one hundred deaths in a population of only eight thousand persons ! Typhoid-carriers, like carriers of cholera germs, are not infrequent as I have already ex- plained. In them the bacilli find a continuing home in the intestines. "Wherever these car- riers go they leave a trail of typhoid and death. From the intestines the bacilli of typhoid fever are prone to travel into the gall bladder, where they have been found in pure culture over fourteen years after the fever. They are the cause of dangerous infections of the gall bladder which always require operation. But Medical Research — how often shall I repeat this good news ! — has not been content with discovering the bacillus of typhoid and 105 MEDICAL RESEARCH AND HUMAN WELFARE how this has caused severe epidemics. One of its greatest and most beneficent triumphs has been the discovery of a preventive vaccination with the typhoid antitoxin. The value of this preventive inoculation is best shown by some statistics. I take the following figures from the Annual Report of the Surgeon-General of the United States Army: — Typhoid Fevbb in the United States Abmt Year Cases Deaths 1906 210 12 1907 124 7 1908 136 11 1909 173 16 1910 142 10 Anti-typhoid vaccination made compulsory 1911 70 8 1912 27 4 1913 4 1914 7 3 1915 8* * 4 in the United States; i in Havaii. The Surgeon-General of the Army calls atten- tion to the fact that " among all the troops . . . on the Mexican border and in Texas • . . not a single case of typhoid has occurred in an inocu- lated man since June 4, 1915." The Reports of the Surgeon-General of the 106 TYPHOID FEVER United States Navy furnish the following similar figures : — Year Cases Deaths 1909 189 17 1910 193 10 1911 222 15 Anti-typhoid vaccination made compulsory 1912 57 2 1913 22 4 1914 13 1915 15 1 "I have no hesitation in saying," adds the Surgeon-General, "that the practical elimina- tion of typhoid [from the Navy] ... is due almost in toto to this vaccination. " At the beginning of the present Eiwopean War the armies on both sides were not pro- vided with sufficient vaccine and a consider- able number of typhoid cases occurred. By the end of 1915 there were twenty-six labo- ratories in Germany making the vaccine, and the entire German army had been protected. All soldiers were revaccinated after six months. Many millions, therefore, were inoculated. The "Miinchener medicinische Wochenschrift," in May, 1916, stated that not a single death had followed the inoculations. Rarely does any 107 MEDICAL RESEARCH AND HUMAN WELFARE serious reaction follow. By December, 1915, there were occasions when, in both the army and among the population of a large town in which the army was quartered, there was not a single case of typhoid. Up to August 25, 1916, it was officially stated that among the British troops in France the percentage of deaths among the men inoculated against typhoid was 4.7 per cent; among the uninoculated 23.5 per cent. About ninety-five per cent of the soldiers have been inoculated. The percentage of cases of typhoid among the inoculated is, therefore, exceedingly small com- pared with the percentage of cases among the uninoculated. The latest and still more remarkable typhoid statistics were presented in the House of Com- mons on March 1, 1917, by Mr. Forster, as follows: The last weekly returns showed only twenty-four cases in the four British Armies in France, Salonica, Egypt, and Mesopotamia. He added that "the total number of cases of typhoid fever in the British troops in France down to November 1, 1916, was 1684, of para-typhoid, 2534, and of indefinite cases, 353, making a total of 4571 of the typhoid group." 108 TYPHOID FEVER In the Spanish War in 1898 (see table be- low) every fifth man contracted typhoid fever. If the same ratio (1 to 5) had held in the British army alone in the present war there would have been 1,000,000 cases! The actual number has been less than one case in every thousand men instead of one in every five men. It may be truthfully said, "Typhoid fever in war has practically disappeared." At the be- ginning of the present war Germany had pro- vided many large hospitals for the expected typhoid cases. These hospitals have never been filled. Most of them have been used for other purposes. Look at the extraordinary contrast between the typhoid record of the four prin- cipal wars of the latter half of the nineteenth century and the present war. Nothing could possibly be more convincing. Research has conquered typhoid. Typhoid Fevek m Five Wabs in Fifty Yeabs Cases Deaths Civa War, 1861-65 79,462 29,336 Franco-Prussian, 1870-71 74,205 8,904 Spanish-American, 1898 20,738 1,580 Boer War, 1899-1902 58,000 8,000 War of 1914-16 Almost none (see text) when compared with the millions engaged 109 MEDICAL RESEARCH AND HUMAN WELFARE In our civilian population the story is very different. There has been a great improve- ment from 1900 when the death-rate was al- most 40 per 100,000 — reduced to 12.4 per 100,000, or only one third as many, in 1915. But then there were over eight thousand deaths from typhoid in 1915 in the registration area of the United States, which contains only two thirds of the entire population. For the whole country, therefore, the deaths were approxi- mately over twelve thousand. Had there been universal civilian vaccination I doubt if there would have been five hundred deaths instead of twelve thousand. Twelve thousand deaths mean also certainly largely over one hundred thousand cases of anxious and expensive illness, almost all of which would have been prevented. TYPHUS Not long since I listened to the story of the conquest of typhus fever in Serbia as told by Dr. Richard P. Strong, of Harvard. My won- der grew from sentence to sentence as he re- counted the ravages of the fever, the obstacles to be overcome, the scant weapons he had with which to fight the fever, and yet he and his 110 TYPHUS splendid band of doctors and nurses sur- mounted every difficidty and won a great vic- tory. Imagine the situation — a whole nation, half famished, half clothed, infested with lice, thousands of patients to be fed, disinfected, cleansed, re-clothed, and nursed through a long illness in few and ill-furnished hospitals, with no clean potable water to be had, and a lamentably small staff of nurses. The whole civic life was destroyed; the military necessa- rily predominated. Not the least obstacle was the difficulty of utilizing an unknown language. Yet even amid all war's alarms, he and one of my old Jefferson boys and their colleagues and heroic nurses finally banished typhus. But the grim fever had its reprisals. Death claimed its toU of not a few of the finest of those brave doctors and nurses. Typhus fever, or, as it is variously called "ship fever," "jail fever," "hunger fever," — ominous names, — at times has been a verit- able pestilence, destroying thousands. Its cause was entirely unknown and its mode of transmission most obscure until modern science discovered them. In 1909 Anderson and Goldberger in Amer- ica, and NicoUe in Algiers, independently dis- 111 MEDICAL RESEARCH AND HUMAN WELFARE covered that the body louse becomes infected by feeding on the blood of typhus patients and in turn infects humans by its bite. How diffi- cult a problem the destruction of the body lice was may be imagined from the statement of Dr. Hall, Texas State Quarantine Officer, that the physician should wear silk underwear, as the louse will not deposit any eggs on silk, and should take three baths a day, the last being of gasoline. The lice will outlive even washing with soap and water — often, I fear, also a se- vere and novel ordeal for the Serbian patients. Among the Americans who have confirmed this discovery I wish to mention with especial honor two of our fellow-countrymen, Drs. Conneff and Ricketts. At the threshold of most promising careers they fell at their posts, and have added two more names to the mar- tyr-roU of science. They fuUy understood their great danger, but they cheerfully made the great sacrifice. Plotz, of New York, has probably discovered the germ of typhus and, in conjunction with Olitzky and Baehr, has possibly found an antitoxin. In Serbia, Bulgaria, and Volhynia, 8420 persons, especially those most exposed to the infection, were inoculated with this anti- 112 MALTA FEVER toxin, and during the four months of the epi- demic only six fell ill with typhus and only two died. If further observations confirm this dis- covery another laurel crown will adorn the brow of Research Medicine. MALTA FEVER The story of the elimination of Malta fever from the British aripy and navy and the native inhabitants of Malta is a striking example of the benefit conferred by Medical Research. That lovely island in the Mediterranean, famous in the Scriptures, in ancient history, in the legends of the Crusades, and in modern military geography and strategy, should be one of the healthiest spots on the globe. Yet a peculiar fever was so common as to have re- ceived its name from the island. Assignment to duty there was feared alike by the men and the officers. Indeed, it was more feared by the officers and their families than by the men. Clean, airy quarters, excellent sanitation, far from preventing seemed to invite the fever, for in the officers' quarters it attacked three times as many proportionately as among the men in crowded barracks. Among a garrison of seven lis MEDICAL RESEARCH AND HUMAN WELFARE thousand soldiers there were an annual average of three hundred and twelve cases and in the navy a similar proportion. As late as 1905 there were 643 cases. The illness was a very painful one with great emaciation and weakness. Very many had to be invalided home. The germ is an extremely minute organism and was supposed to be borne by the air. In 1904, aroused by the ravages of the fever, the Royal Society sent a commission to investigate. They examined exhaustively the climatic con- ditions, the water-supply, the drainage, the water in the harbor, the slums, the various kinds of dwellings and their possible defects. Then the air was examined. The mosquito was found to be guiltless. Finally, the food-sup- plies were investigated, and at the end of three years' steady work they discovered the way in which perfectly healthy people living in almost ideal conditions became infected, and at once the disease vanished. Among other foods the milk-supply was examined. This was furnished by about twenty thousand goats. These goats, like the mosquitoes and the various "carriers" already described, were apparently perfectly healthy, and, therefore, for a long time had escaped sus- 114 TETANUS picion. The milk of some thousands of goats was examined. One half of them were infected and in a large number of them the milk was full of Malta fever germs. Monkeys fed on the milk for one day fell ill of the fever. Even one drink of infected milk would give it to a hu- man patient. Goats' milk was then prohibited. Note the result. In 1905 there were 643 cases. In 1907 there were only seven cases. From 1910 to 1913, in four years, there were only twenty-two cases in all, all traced to goats' milk. Some of these few had not been infected in Malta, but were immigrants from other in- fected places. In 1911 Gentry and Ferenbaugh, in south- western Texas, discovered Malta fever on some great ranches and confirmed its origin from the goats. TETANUS What a world of terror is contained in that one word — "Tetanus!" "Lockjaw" is the popular name for it because the earliest symp- tom is a difficulty of moving the lower jaw. The stiffness soon increases so that it is im- possible for the patient to open his mouth — 115 MEDICAL RESEARCH AND HUMAN WELFARE hence the name "lock-jaw." But the disease does not stop there. The spasms, first mani- fested in the muscles of the jaw, spread all over the body and may become so severe as to bend the body backward like a bow so that in severe cases the sufferer only touches the bed by his heels and his head. A robust arm can be thrust under the arched body without touch- ing it. Never shall I forget a fine young soldier dur- ing the Civil War who soon after Gettysburg manifested the disease in all its dreadful horror. His body was arched as I have described it. When at intervals he lay relaxed, a heavy foot- step in the ward, the bang of a door, would in- stantly cause the most frightful spasms all over his now bowed body and he hissed his pitiful groans between tightly clenched teeth. The ward was emptied, a half-moon pad was hung between the two doorknobs to prevent any banging; even the sentry, pacing his monoto- nous steps just outside the ward, had to be removed beyond earshot. You have all experienced the severe pain of strong cramps in the calf of your leg or sole of your foot, and know how almost unbearable a severe cramp becomes so that you even may be lie TETANUS obliged to cry out. Imagine, not the calf mus- cles only, but every muscle of your head, neck, body, arms, fingers, legs, toes, gripped in cramps ten, twenty-fold more severe. More- over, what makes one shudder the more is the fact that, as in this poor young fellow's case, his mind was as clear as yours or mine at this moment. Nothing lessened or even blurred his capacity to feel the horrible pain. The spasms became more and more severe, the intervals shorter and shorter; it did not need even a foot- fall now to produce the spontaneous cramps, until finally a cruelly merciful attack seized upon the muscles of his throat and then his body was relaxed once more and forever. He had been choked to death. The first time I saw the statement in a medi- cal journal that lockjaw was of telluric origin I recall vividly my entire incredulity. That it came from the ground, the earth on which we walked, seemed to me incredible. We had known for many years that hostlers and others who worked among animals, especially horses, were far more often attacked, and everybody was familiar with lockjaw as a result of tread- ing on an old rusty nail. These were undoubted facts, but no one knew the reason for them. 117 MEDICAL RESEAHCH AND HUMAN WELFARE Finally, in 1884, Nicolaier demonstrated the curiously shaped bacillus like a tack or a drum- stick. (Plate I, Fig. 6.) Then it was found that the bacillus infested the intestines of the horse and other animals. Yet, strange to say, here is another instance of a microbe which is entirely harmless to its host, the horse, so long as it is limited to its normal home, the intestines, but once let it get into a wound, even of a horse, and it is deadly: tetanus develops and with a ter- rible mortality both in men and horses. In the Civil War the mortality was just short of nine out of every ten patients. We now understand why such a large number of cases of lockjaw were seen at the beginning of the present war. France and Flanders had been roamed over by animals ever since before the days of Caesar's Gallic War, and the ground was saturated with the tetanus bacilli. The soldiers in the trenches had the earth grimed into their clothing. It coated their bodies. When hit by a piece of shell, a bit of clothing or of their muddy skin was driven deeply into the wound and with it the germs of tetanus. Our Fourth-of-July tetanus tells the same story and well shows another feature of this special bacillus. Some germs grow best in the 118 TETANUS air with plenty of oxygen. We call them air-liv- ing, i.e., aerobic. To others oxygen is an enemy. They grow best without air; i.e., they are named an-aerobic. The germ of tetanus is one of the anaerobic kind. When the small boy is wounded by the little bullet of the toy pistol, or when he steps on a rusty nail on the highway, a little blood escapes for a few minutes, then clots, soon dries, and so completely closes the little wound. The oxygen no longer can get access to the interior of the wound. The con- ditions are ideal for the tetanus germs to grow. The poison reaches the nerves in the woimd, travels to and then up the spinal cord, and soon every muscle in the body is in the horrible spasms. But Medical Research again has elaborated an eflScient preventive. The prohibition of the toy pistol has greatly lessened the number of cases and the practically universal use of the antitoxin as a preventive in all well-equipped hospitals has almost given the coup de grace to Fourth-of-July tetanus. The Great War has triumphantly established the value of the antitoxin. At first, when the supply of antitoxin was wholly inadequate for such huge armies, there was a considerable .119 MEDICAL RESEAKCH AND HUMAN WELFARE number of cases of tetanus. But now for a long time there has been an ample supply of the antitoxin. As every wound is an infected wound and every case may develop lockjaw, every wounded soldier at the very first practicable mo- ment is given a full preventive dose of the anti- toxin by a hypodermic syringe. The result is that while no actual percentages or figures have been published, tetanus, it is stated, has almost disappeared. At the Second German Siu-gical War Congress in April, 1916, the President declared that, in the year just passed, tetanus had been "completely suppressed" in the German army. The wounded who have lain between the lines for hours or even a day or two are liable to develop lockjaw, but the men who promptly received a hypodermic of antitoxin go practically scot-free. What a happy — indeed, one may say what a splendid — result from Medical Research! LEPROSY Dr. Victor G. Heiser, I hope, may be the conqueror of leprosy. We are all familiar with the pathetic cry in the Book of Books, "Unclean! Unclean!" Well 120 LEPROSY does the repulsiveness of its victims warrant the cry. Though originally only a disease of the Orient, it has slowly spread all over the world. We have a considerable number of cases in the United States. The first step in its eradication is segrega- tion. Heiser — who was the eflBcient Director of Health of all the Philippines for ten years — persuaded practically all the lepers in the Philip- pines voluntarily to go to the Island of Culion, where he built a town, officered,policed, cleaned, and amused by lepers. They have even their own currency (a token cmrency for use only in Culion itself), a town hall for plays, lectures, — "movies," I feel sure, — and other recreations. This segregation prevents any new cases from arising by contact. Chaulmougra oil has long been known as a remedy which has greatly benefited leprosy, but never cured it, since the stomach after a time revolts and the patient can no longer take it. Heiser has discovered a means by which the oil can be given hypo- dermically and continuously. The treatment requires over a year — sometimes two years. When I last saw Dr. Heiser he told me this oil was being used in many places in the East, that two score patients had remained well with- .121 MEDICAL RESEARCH AND HUMAN WELFARE, out treatment" for two years, and that very many more were on the way to cure. As a resiilt of this favorable outlook, the Rockefeller Health Commission has sent Dr. Heiser all around the world to obtain the co- operation of various govermnents in this treat- ment of leprosy, and at the same time in the cure of the hookworm disease. K, as seems probable, he can obtain this cooperation, he is strongly inchned to think that the eradication of leprosy and hookworm disease is a possibility. INTERNAL SECRETIONS AND THE DUCTLESS GLANDS I must now ask your close attention to a very obscure subject even to medical men. Yet it is a subject of intense interest and vital importance, the knowledge of which has been forced upon the profession in the last twenty years. I mean the internal secretions and the ductless glands. The Uver, the pancreas, the kidneys, the sal- ivary and other similar glands discharge their secretions by tubes called "ducts," by which their secretions reach the intestines, the blad- der, the mouth, etc. In 1848 Claude Bernard 122 INTERNAL SECRETIONS AND DUCTLESS GLANDS discovered that the liver not only secreted bile, which was passed into the intestines through its duct, but that it had a second function. It secreted sugar, which was discharged, not by any duct, but into the blood itself as it passed through the Uver. This was a wholly new idea — that any organ could produce two secretions, one discharged through the duct and the other added directly to the blood. But while this discovery caused a great sen- sation in the scientific world, tire idea that there might be a number of other glands, which, having no duct, produced oiJy the second sort of secretion which reached the venous blood in its coiuTse through these ^ands, was scarcely entertained. In 1873 Sajous, of Philadelphia, insisted on the existence and impcfftance of these "internal secretions," as they 'were properly called, but the greater part of medical men were inclined to think the idea rather fantastic and did not take it seriously. Meantime a few men were experimenting especially on the thyroid gland in the neck, a gland the enlargement of which you all know as a "goiter." They found that its internal secretion played an important part in the animal economy, as I shall show you. 123 MEDICAL RESEARCH AND HUMAN WELFARE Finally, as Adami says, "the doctrine of in- ternal secretions . . . came into its own" by the convincing experiments of George Mui^ay on the thyroid in 1895. [The best recent book — and a very remarkable one — is " The Thy- roid Gland in Health and Disease," by Robert McCarrison, London, 1917.] "All this seems, no doubt, interesting to the physiologist," you say, "but is it really of any fundamental importance to us?" In reply let me relate a personal experience — one of those terrible tragedies of surgery which unavoidable ignorance inflicted upon me. In 1890, after I had long practiced anti- sepsis and in this particular case had used every precaution known to science, I removed the thyroid gland for a large goiter. Everything went well during the operation and for twenty- four hours afterwards. Then set in what is called "tetany." The yoimg woman became restless, constantly tossed about, could not sleep, became excessively excitable, at times almost maniacal, and death quickly followed. Never have I been able to banish the bitter rec- ollection, which even now at times surges up in my mind, that I was unwittingly her execu- tioner. No one who has not gone through such 124 DTFERNAE SECBETIONS AND DUCTLESS GLANDS a heart-breaking sorrow can know its wearing grief. One year later — too late, alas! to be of bene- fit to her or to me — the fact that tetany, fol- lowing an operation for goiter, is due to the removal of the little "parathyroid glands" was first demonstrated by Gley. These little glands, which I had ignorantly removed, were only dis- covered in 1880 by Sandstrom. They consist of two, three, or four oval bodies lying closely be- hind the thyroid gland. They are with difficulty distinguished from it. They are only one quar- ter of an inch long, yet they are essential to life. This has been demonstrated by their inten- tional removal ia animals, and their uninten- tional removal in human beings as in my case. If one or two are left, the patient can live, but removal of all is surely fatal. But when I per- formed the operation just described, all of us were utterly ignorant of their vast importance. In fact the idea seemed almost absurd that such insignificant little bodies, scarcely seeming to be more than masses of fat no larger than a small pea, could be of any serious importance. But as I have shown you, life and death hung upon the knowledge of the function of these parathyroid glands. 125 MEDICAL RESEARCH AND HUMAN WELFARE Now, having learned their supreme import- ance we have also learned how to avoid their removal and thus to avoid a fatal error. How else can we learn the terribly important function of these little glands except by experi- ments on animals? Even now their exact physi- ological influence is too uncertain to make any positive statement advisable beyond that al- ready mentioned, that the removal of all of them is fatal. Is it not a duty to learn all we can about them as quickly as possible, and not only to learn all we can about the parathyroids, but about all the other ductless glands as to which we still know so little? Do you wonder that we surgeons, physicians, physiologists, and obstetricians yearn intensely, yea, with all our souls, for "more light," so that we shall not innocently and in fact un- consciously sacrifice the lives of our patients that is, of you and your children? What a chapter could be written on the "Calamities of Unavoidable Ignorance!" What are the glands of internal secretion? There are two very large glands of double se- cretion, the liver and the pancreas. They se- crete respectively bile and pancreatic juice. These secretions reach the upper intestine di- U6 INTERNAL SECRETIONS AND DUCTLESS GLANDS rectly through their regular ducts and are es- sential to normal digestion. Both of these two great glands also have an internal secretion which escapes directly into the blood and as- sists in the transformation of sugar into alco- hol and carbonic acid. The spleen is also a ductless gland, but in spite of its size, as large as a fist, it is not es- sential to Hfe. It has been successfully removed many times. But I pass it by simply because we know so little about it, and that in spite of constant study and experiment. The other ductless glands with one exception are all very small. The smallest seem even to be the most important. Some are single and Ue in the mid-line of the body. They comprise, first, the pituitary gland, or "hypophysis," at the base of the brain and about two and a half inches back of the root of the nose. The name "pituitary" is derived from the old er- roneous notion that it secreted the "pituita," the Latin term for the nasal mucus. That we now know comes from the nasal mucous mem- brane. Next comes the pineal gland, again at the base of the brain and about four to five inches back of the root of the nose. This gland was 127 MEDICAL RESEAKCH AND HUMAN WELFARE again erroneously declared by the older anato- mists to be the "seat of the soul." Its function — and it surely must have one — is practically unknown to us. A third is the thymus gland, situated just be- hind the top of the breast-bone. This is only a temporary organ. It is about two inches long and at birth weighs half an ounce. It enlarges somewhat during the first two years of Ufe, then ceases to grow, and at about the period of puberty rapidly shrivels up, but never wholly disappears. Its function is very obscure, but it ministers in some unknown way to the needs of the body, especially as to development and growth up to the age of puberty. During early childhood it is sometimes the seat of a rare but serious and sudden change which is ahnost al- ways rapidly fatal. Its removal in animals impairs the develop- ment of the bones especially due to a diminished amount of phosphate of lime. A condition like rickets ensues, the bones easily bend, and are readily fractm-ed. Its removal in hens causes them to lay eggs without shells. If a fresh thy- mus is re-implanted in animals from which the original thymus was removed, the normal processes are restored. In idiots the thymus is ,128 INTERNAL SECRETIONS AND DUCTLESS GLANDS generally absent, as is shown by post-mortem examinations. Other ductless glands are bilateral, e.g., first, the parathyroids, of which I have already spoken. Secondly, the adrenal or supra-renal glands are also bilateral and are of great importance. They are situated one at the upper end of each kidney. Of these I shall speak later. A few other glands of internal secretion exist. Some, seemingly unimportant, of whose func- tion we are at present wholly ignorant, may easily be found to be of great importance when we really learn their uses. Certainly they can- not be found in human beings and many ani- mals and yet be useless. But I must ask your further close attention to some of the results of Medical Research as to the thyroid, the pituitary, and the adrenal glands. These are of great interest and of great practical importance. The pituitary, the para- thyroids, as I have already shown, and the ad- renals, all three are absolutely essential to Ufe and the thyroid is essential to normal life. Lack of the normal secretion of the thyroid gland when it is congenital — that is, existing from birth — gives rise to the condition called 129 MEDICAL RESEARCH AND HUMAN WELFARE te cretinism," amounting almost to idiocy. When it occurs in adults, it causes a condi- tion called "myxedema" — a degenerative con- dition of mind and body. In these conditions of too little of the internal secretion of the thyroid gland, attempts have been made — and in not a few cases with bril- liant success — to supply the deficiency by ad- ministering an extract of the thyroid glands of sheep. This is a notable contribution of Medical Research to Human "Welfare. The same extract has been used in cases of apparently normal young persons, whose physi- cal growth, however, has been retarded for some unknown cause. The most remarkable instance I know of its benefits — a wholly exceptional case — was re- corded by Dr. George A. Gibson, of Edinburgh, just before "the curfew of his life was to quiver on the evening air," to use his own poetic and prophetic expression. If I had not known him well personally and could vouch for his scrupu- lous exactness, I should be disposed to think him rather careless of the truth. A lad of eighteen, who had set his mind on entering Woolwich, the Enghsh West Point, was only four feet and eleven laches in height. il30 INTERNAL SECRETIONS AND DUCTLESS GLANDS This was'four inches below the required height and the examination was only six months away. The ease seemed hopeless, yet following the administration of thyroid extract, under Gibson's careful supervision, in six months the lad grew seven inches in height! And what was most gratifying, his mental development was not in the least interfered with, as he attained high rank in his classes. But such a powerful remedy must never be used except under con- tinuous medical care. When there is an excessive secretion from the thyroid gland there results that especially dangerous form of goiter known as "exophthal- mic goiter" or "Graves' disease." The pituitary gland or hypophysis is only as large as the tip of the httle finger and weighs only seven to eight grains. Small as it is, it is divided physiologically into a front, middle, and back portion, differing anatomically and physiologically. The front part is essential to life. Its re- moval is quickly fatal. When diseased, it causes the overgrowth of the bones, especially of those of the face and the extremities, a con- dition which not very seldom develops in adult life and is known as " acromegaly." Very slowly 131 MEDICAL RESEAKCH AND HUMAN WELFARE the bones of the face become leonine, or greatly enlarged, as do also those of the fingers and toes. The secretion of the middle and back part activates the heart and stimulates the kidneys and the milk glands. It also lessens the caliber of the blood vessels and thus influences the blood pressure in a manner similar to the secre- tion of the next glands to claim our attention. The adrenals are two glands lying on the upper end of the two kidneys, and hence called "ad-renal" or "supra-renal" glands. They are slightly larger than the last joint of the thumb. Their secretion is called "adrenalin" or "adrenin." These glands have been known ever since 1564, but our accurate knowledge of their function and the chemical isolation of their secretion goes back less than a score of years. Their active principle or secretion was first isolated in 1901 by Takamine, a Japanese Working in New York. It is constantly being secreted in small amounts. It keeps up the normal tone of the blood vessels and the normal percentage of sugar in the blood. How extraor- dinarily powerful it is, is shown by the fact that a solution of one part in 200,000,000 — that is, one drop in one hundred barrels of water — when applied to the intestine of a living rabbit 133 INTERNAL SECRETIONS AND DUCTLESS GLANDS is suflBcient to stop the movements of the intes- tines! It increases the activity of the heart. It shifts more or less blood from the great blood vessels of the abdomen — note this with care — to the heart, lungs, muscles, and central nervous system. This enables the body as a whole to respond to sudden physical and mental emer- gencies, requiring quick action and unusual exertion, for fight or flight — an "emergency function" as Cannon well names it. Thus fear, rage, or pain causes instant and unusual pour- ing out of adrenalin and mobilizes our physical and mental forces for use in such emergencies. This influence of fear, acting on the adrenals, the thyroid, and possibly the liver, is, I think, the explanation of the unusual phenomena in the case of a little girl nine years old under my care some years ago in the Jefferson Hospi- tal. She weighed about fifty pounds. A year earlier her clothing had caught fire and she had been dreadfully burned. I was obliged to am- putate her left arm at the shoulder joint- She quickly recovered and was waiting to go home. One night a large fire broke out, only a block away; the flames were visible through the great windows of the ward, and flooded it with hght. She woke up suddenly screaming with 133 MEDICAL RESEARCH AND HUMAN WELFARE terror, thinking that the ward was afire and that her former terrible accident might occur again. Her temperature, which had been nor- mal for days, had suddenly risen to 104.5° F. All her forces of mind and body were mob- ilized for escape. After a time, when her fears were quieted, she fell asleep. In the morning her temperature had fallen to normal. Her adrenals had raised the temperature of her fifty pounds of flesh six degrees in almost as many loainutes! Adrenalin is now frequently used in surgical operations to raise the blood pressure when danger threatens from loss of blood and' shock. The experimental methods by which the functions of these various glands have been discovered are chiefly by removal of part or all of a gland if it is single, or by removal of one or more if multiple, and then observing the results. These vary when the experiment is done on young, growing animals and on adult animals. Such experiments are obviously utterly impos- sible in man. Occasionally also cases occur in humans and animals of tumors of these glands or of degenerative processes, which add to our knowledge. By many experiments and observations two other facts have been ascertained. 134 INTERNAL SECRETIONS AND DUCTLESS GLANDS First, that the glands of internal secretion, about which we really know as yet but little, are all more or less closely interrelated and form a complex system of their own. Some day we may hope to understand this system com- pletely, instead of very imperfectly as at pres- ent. This interdependence is well known by a clever experiment, again not possible in man. It has an undoubted significance which is as yet not understood. The small amount of adrenalin normally poured into the blood evokes a marked current of electricity in the thyroid gland. Clamping the veins from the adrenal glands, thus preventing the return of the venous blood from the adrenals, contain- ing, of course, this small amount of adrenalin, into the general circulation inamediately stops this current of electricity. When the clamp is removed and the venous blood containing the adrenalin again reaches the general circulation, the electrical current promptly reappears. The second and very recent discovery is the existence in the secretions of these ductless glands of what are called "hormones"; i.e., "stimulators" or "excitors." These substances, secreted by one gland, stimulate other, dis- tant, and apparently wholly independent, 135 MEDICAL RESEARCH AND HUMAN WELFARE glands into activity. In fact, without the secretion of gland number one, gland number two cannot function. If disease prevents the secretion of the hormone by gland number one, the function of gland nimiber two is altered or abolished. Is it not strange, passing strange, that the human body, "a harp of a thousand strings, shoiild keep in time so long?" Several of these hormones or exciters are now known, but we are only at the beginning of such researches. I have dwelt at greater length and in greater detail on these curious glands because several of them, as I have shown you, are essential to life, because the researches into their functions well illustrate the methods of Medical Re- search, and finally, because, if even our very imperfect knowledge has been of much benefit to man, it is evident that complete knowledge will be far more useful. MEDICAL RESEARCH IN DISEASES OF ANIMALS I have far too little time left for the re- searches into the diseases of animals. These diseases seriously affect Human Welfare, for 136 MEDICAL RESEARCH IN DISEASES OF ANIMALS they often attack humans and destroy their lives. They cause enormous economic losses to the community, as I shall show. They lessen the number of our draft animals. They dimin- ish seriously our food-supply of meats, fats, milk, butter, cheese, and eggs, and affect the supply of wool and hides for our clothing. Finally, they diminish our recreations and our pleasures. Five thousand millions of dollars are in- vested in domestic animals in the United States. In 1912 there were lost six and a half roillions of swine, two millions of cattle, two and a half millions of sheep, and half a million of horses and mules. Reflect also for a moment on the sufferings inflicted by relentless Na- ture upon these millions of animals which Medical Research is endeavoring to mitigate or abolish! The Department of Agriculture in 1915 computed the following astonishing table of the direct annual losses from animal diseases in the United States simply ia terms of money value, to say nothing of the sufferings of these patient animals, of the dangers to human life, or of our diminished food and our clothing supplies : — 137 MEDICAL RESEARCB AND HUMAN WELFARE DiB3e:cT Annual Losses based on BETUBxa fob Thibtt Ybabs fhom Animal Diseases in the United States Hog cholera $75,000,000 Texas fever and cattle ticks 40,000,000 Tuberculosis 25,000,000 Contagious abortion 20,000,000 Blackleg 6,000,000 Anthrax 1,500,000 Scabies of sheep and cattle 4,600,000 Glanders 6,000,000 Other live stock diseases 22,000,000 Parasites (trichina and others) 5,000,000 Poultry diseases 8,750,000 $212,850,000 The chief diseases of animals which man is in danger of contracting are anthrax from sheep and cattle, hydrophobia from dogs, wolves, coyotes, etc., the trichina parasite in pork, glanders from horses, and tuberculosis from cattle. Hydrophobia, anthrax, and other similar diseases I have already considered in tracing Pasteur's wonderful career. Fortunately an- thrax is the least destructive of all those named in the above table. In man it is rare in the United States. Personally I have seen only one case. The trichina spiralis is well known to all 138' MEDICAL RESEARCH ESf DISEASES OF ANIMALS intelligent people. It was first discovered by Richard Owen eighty years ago. Its life his- tory was fully studied by Virchow in 1865-66 when I was a student in his laboratory. It is a spiral worm which encapsulates itself in the muscles of swine. "When pork is eaten raw by man, the gastric juice dissolves the capsule or envelope, sets free the worm, which then finds its way to the muscles and other organs, even to the brain, and often destroys life. For years our Government has had extensive and expensive laboratories in order to examine with low-power microscopes all our hog, cattle, and other exports for trichina, tuberculosis, etc. How enormous and also how imperative this work is we appreciate when we learn that in 1916 the Bureau of Animal Industry re- ported that over 62,000,000 animals were ex- amined in 875 laboratories in 247 cities by 2554 employees; 11,800 live animals and 738,000 parts of carcasses were condemned. The condemned carcasses and parts were de- stroyed or converted into fertilizers. Without this inspection such exports are barred out of other countries. Our own citizens are far more exposed than are foreign consum- 139 MEDICAL RESEARCH AND HUMAN WELFARE ers, for state and city inspection is often ineffec- tive and sometimes non-existent. "Country sausage" may easily be less certainly safe and wholesome than if made in a city which enforces a proper inspection. Happily, in this country we almost never eat pork products raw, as is common in Germany and hence our people suffer but little damage to health and life. Thorough cooking kills the parasite and re- moves the danger. But for commercial purposes Medical Re- search has shown that the microscope is not a complete protection from the trichina, for only small fragments of tissue from the several places where the parasite is usually foimd are examined. Latterly the Department of Agri- culture has found that freezing, i. e., cold stor- age at 5** F. for twenty days kills the worm. This method reaches the parasite wherever it is located, is far more effective, and also less ex- pensive than the microscopic inspection hitherto in vogue. But even then I personally would prefer to "make assurance double sure" by thorough cooking — employing both freezing and fire to make a trichinous purgatory. But until Medical Research discovered the parasite, learned by experiment its life history, 140 TEXAS OR TICK FEVER and discovered the means of prevention, many human lives were sacrificed. TEXAS OR TICK FEVER Though not contagious for men this deserves mention for two reasons. First, it ranks sec- ond in the table of economic losses to our coun- try, being responsible for a loss of $40,000,000 a year, and by so much also it reduces our food- supply. In both these ways it affects human health and human welfare. In addition to this it is notable as the first disease which, by ex- perimental research, was discovered to be an "insect-borne disease." In 1889 Dr. Theobald Smith read a paper describing most lucidly the experiments by which he had discovered the cause of this fever and the mode of its trans- mission. His experiments were made by pastur- ing healthy cattle in enclosed fields on which cattle which had died from Texas fever had been pastured, just as Pasteur, you will remem- ber, investigated anthrax. The healthy cattle in turn soon fell ill and died. His experiments took place ten years after the first book on medical thermometry had been published, and Smith points out that if the thermometer had 141 MEDICAL RESEARCH AND HUMAN WELFARE not been used, the rise in temperature, its earliest symptom, would have entirely escaped notice. He found in the blood, liver, and other organs the parasite which caused the fever. Smith and Kilbourne then discovered the mode of transmission. That ticks were the medium had long been suspected. They proved it. They bred ticks in captivity. The eggs hatched out normally, but, strange to say, it was found that the insects failed to develop unless placed on cattle, their special foster- parent, so to speak. The young ticks just hatched out at first were not placed on cattle. They were watched from December to May, and during all this time they merely lived, but did not grow. In May, the moment they were placed on cattle, they began to develop, and the first moult took place within a week. Three weeks later and after a second moult, the tick falls to the groimd and dies after lay- ing from one thousand to two thousand eggs. In two weeks or more the new ticks are hatched and again seek the cattle and the cycle begins again. When the disease reappeared, the sec- ond summer of Smith's experiments, — this remember was almost thirty years ago, — like a flash the conviction came to him that he had 142 TEXAS OR TICK FEVER witnessed a new fact, the rdle of insects in the causation of disease. After the tick had infected the cattle, the parasite begins the second phase of its hf e in- side the blood corpuscles of the cattle. The red blood cells are destroyed by millions upon mil- lions daily and death soon follows. In acute epidemics the disease kills from ten to ninety per cent. Besides this it lessens the value of the survivors, and retards their growth in size and weight. The ticks are killed by "dipping" the infected animals in an arsenical prepara- tion. A tick-infected steer weighing 730 pounds when thus cured gained in two months 385 pounds in weight with a corresponding increase in value to its owner and to our dinner tables. The infected areas of land are so large that widespread quarantine over the infected areas is still required. Since inspection began over 284,000 square miles have been released from quarantine, being free from infection, but 253,000 square miles are still under the ban. This shows what a huge task oiu- Bureau of Animal Industry still has on its hands in this one disease alone. Millions of cattle have to be inspected every year; over sixteen and a quar- ter milUons were examined last year. 143 MEDICAL RESEAKCH AND HUMAN WELFARE As this was the first disease which was proved to be spread from one animal to another by an insect, it strengthened the suspicion that the mosquito might harbor the parasite of ma- laria, and later that yellow fever was spread in a similar manner. Now we know not only that these diseases are insect-borne, but that the tsetze fly carries the fatal sleeping-sickness of Africa, that Uce spread typhus fever, and fleas spread the plague. These studies by Smith and his associates, fol- lowed by those of the American Yellow Fever Commission, proving that mosquitoes carried malaria and yellow fever, not only contributed enormously to the welfare of man and animals, but made the Panama Canal a possibiUty. What an imposing by-product! What a satisfaction it is that the Rockefeller Foundation has given a million, with more to follow, to carry on their splendid studies in animal diseases and has placed at the head of this department Theobald Smith, the most distinguished living student and discoverer in animal diseases. 144 HOG CHOLERA HOG CHOLERA This fatal disease ranks first in the table of losses from animal diseases in the United States, being responsible for an annual loss of $75,000,- 000. This huge diminution of our food-supply is one of the reasons for the high cost of Uving. It is a highly contagious disease, having fre- quently a mortality of seventy to eighty per cent; sometimes every hog dies. The cause of the disease is one of those strange germs so diflicult and even impossible to find or to cultivate. They are so small as to pass freely through the finest filters which prevent the passage of the vast majority of germs, such as those of typhoid, diphtheria, etc., small and microscopic as the latter are. Yellow fever, smallpox, hog cholera, foot and mouth disease and contagious pleuro-pneumo- nia of cattle are probably all caused by simi- lar germs so small that it may be a question whether we ever can see them. By inoculation experiments, however, we are learning gradu- ally very much about them. After a while we shall certainly discover and as certainly van- quish them. Even now Medical Research has found a 145 MEDICAL RESEAKCH AND HUMAN WELFAEE serum against hog cholera which costs but twenty-five cents a dose. Field tests have proved its value and we may look with confi- dence to the future. . In two thousand hogs on forty-seven farms treated with this serum, eight-five per cent of the hogs which sickened were saved. Of other hogs in the same herds but untreated, only twenty-five per cent escaped. After inocula- tion with the serum, herds exposed to contagion were all saved. In three selected counties the mortality in 1912 was 28.4 per cent; in 1913, in these same counties, the use of the serum cut down the mortality to one fourth (7.7 per cent), and in 1914 to one seventeenth (1.7 per cent). Meantime the number of hogs had in- creased over seventy-five per cent. But I must omit other researches in diseases of animals of the greatest interest and of equally great importance, such as glanders in horses, foot and mouth disease (a very fatal disease of cattle), contagious pleuro-pneumonia, etc., all of which seriously diminish our supply of food and clothing. I must also omit all the diseases of fowls which occasion great loss and again greatly diminish our poultry and egg supply. 146 RESEARCH IN DISEASES OP PLANTS RESEARCH IN DISEASES OF PLANTS Bacteria in Soil and Rocks This subject is exceedingly wide. You see with sadness the destruction of our elms and chestnuts and many other trees by fungi and various other pests. Even as I write, the "white pine blister disease" is threatening to destroy our white and five-leaved pine, with a loss of $350,000,000. You know only too well the many destructive moths which have cost millions even to diminish their ravages, to say nothing of ex- terminating them, which so far has been impos- sible. These losses are not only economic, but esthetic as well. Our knowledge of the bacterial origin of plant diseases began in 1878 when Burrill announced the bacterial origin of pear blight. Twenty years ago, with prophetic vision, Dr. Erwin F. Smith declared that "there are in all probabiKty as many bacterial diseases of plants as of animals." The realization of this predic- tion is well shown by a paper of Dr. Surface, of the Pennsylvania Department of Agricul- ture. In 1916 he described sixty-eight separate enemies and thirty-eight separate diseases at- tacking twenty-four grains, plants, and vege- 147 _MEDICAL RESEARCH AND HUMAN WELFARE tables. It is no wonder that our farmers have suffered such serious losses. K all these dis- eases could be mastered, how enormously would our food-supplies be increased and the cost of living be decreased. Only by incessant and intelligent research can this be accomplished. As I am correcting this proof, the world-wide shortage of food and the consequent danger of hunger and even famine in belligerents and neutrals alike, and even for a time after the war stops, strongly reinforce aU I have said as to the imperative need of Research. Plant bacteria resemble animal bacteria in almost every particular. They obtain entrance through wounds — in Italy not seldom through woxmds of the olive caused by hailstones — some are aerobic; some anaerobic; some attack old tissue, some young; some are water-borne and some insect-bome; some produce gas; they react to stains; they are variously colored, and they have a geographical distribution. I can consider only three aspects of this broad problem. I. Bacteria m the Soil By the researches of WiUarth and Hell- riegel in 1866 and of Schloessing and Miintz 148 BACTERIA IN SOIL in 1878 it was shown that nitrification of the soil was accompUshed by bacteria. Plants re- quire nitrogen, of which there is abimdance in the air, for eighty per cent of the air con- sists of free nitrogen. Plants, however, cannot use this free nitrogen. They must obtain it from its combinations in ammonia and nitrates. There are "bad bacteria," as shown by Pas- teur in puerperal fever, the diseases of wine and beer, etc., and by Lister in the infection of wounds. But there are also "good bacteria." Decomposition is due to bacterial action. Stable manure — a typical form of decomposi- tion — is valuable because of this ammoniacal decomposition, for ammonia consists largely of nitrogen. Every one is familiar with the ammoniacal smell of stables. By manuring the soU we provide our crops with the necessary nitrogen in a usable form. Let me describe a remarkable series of exper- iments in Soil Bacteriology. Soil can be ster- ilized in two ways; fiist, by heating it, or, secondly, by treating it with chloroform or other similar volatile agents. Plants grown in such sterilized soil, it was found, yielded greatly increased crops, but no one knew why until Russell and Hutchins, of the Rotham- 149 MEDICAL RiaEARCH AND HUMAN WELFAKE stead Experimental Station in England, inves- tigated the matter experimentally. ^This re- markable field laboratory, as one may call it, was established by Sir John Bennett Lawes in 1843 with an endowment of $500,000, and has done a wonderful amount of good research work in agriculture. Russell and Hutchins found that heat or chloroform, etc., killed many organisms in the soil, but not all. Those that remained increased enormously. For in- stance, normal soil has seven milHon bacteria to the gram — a quarter of teaspoonf ul. After heating, Russell and Hutchins foimd that there remained alive only four hundred bacteria per gram. But in four days these had increased to six million and later were so much more numer- ous that they were not even counted. These observers also discovered that in unheated soil there were protozoa — very low forms of ani- mal life — resembling amoebae, or the white blood cells — which fed on the good bacteria. When these protozoa were killed by heat or chemically, the good bacteria, their enemies being killed, increased enormously and thus enriched the soil by "fixing" the nitrogen of the air. Hence its increased fertility. Mani- festly we cannot heat all the soil because eight 150 BACTERIA IN SOIL to nine inches of top soil on a single acre weighs about one thousand tons, nor can we chloro- form all of our farms. But Hall, the Rotham- stead^Director, is optimistic and believes that modem science will yet discover a practicable method of fostering the good bacteria in the soil. But besides these free bacteria in the soil, plants possess a special means of fixing the nitrogen of the air. From Roman times the farmer has known empirically that peas, beans, etc., and espe- cially clover, greatly improved subsequent crops, but no one knew any reason for this observed fact till modern science discovered it. On the roots of leguminous plants, peas, beans, and the like, are found certain nodules. These nodules are produced by bacteria living in symbiosis with the plant — that is to say, the plant and the bacteria enjoy a common life. (Plate in,Figs. 1 and 2.) These bacteria fix the nitrogen of the air and convert it into com- pounds which the plant can use. They are Nature's fertilizers. A crop of clover, besides all that which has been utilized in its own yield, leaves a rich legacy of nitrogen behind it in the soil. The United States Department of Agricul- 151 MEDICAL RESEARCH AND HUMAN WELFARE ture now has taken advantage of the above facts and furnishes pure cultures of soil bac- teria in liquid form for "inoculating" the soil of our farms. One method of soil inoculation is by trans- ferring soil rich in bacteria from a prior crop — clover, alfalfa, etc. — to poorer soil, two hun- dred pounds or more of rich soil over an acre of poor soil. The bacteria of the rich soil mul- tiply enormously and are diffused all through the poor soil. A slightly different method is provided for farms with no rich soil. A liquid pure culture of the needed bacteria it sprinkled over one hundred to two hundred pounds of the poor soil and thoroughly mixed. This enriched soil is then spread over an acre of poor soil, when the same process of diffusion goes on. Another and simpler method is to soak the seeds to be planted in a pure culture of the bacteria for a short time in the evening, dry them, and sow them the next morning. But the sun is an enemy of both good and bad bacteria and the treated seed must not be sown in sunny weather. They can be kept for a week or so and still be in good condition, ready to be sown in cloudy weather. 152 Fig 1. Kitrogen-fixing Nodules of the Garden Pea ^H Pl^lll ^^M H y^^^^^^^^K^^^^M ^B H^l ^^^^^^^H^L- ^^^i^:J^^^^^^^^^^^ ^^^^^^^^^1 ^^^^^^^^^^^^^^^^1 ^^H^^^^^^^^H Fig. 3. Fossil Bacteria from Montana PLATE III CANCER IN PLANTS I am glad to bear my testimony to the ad- mirable work of the Department of Agriculture. We have right here at Brown one of its most useful laboratories in the Bureau of Plant Pathology for investigating the diseases of trees. No other department of our Govern- ment is doing better work for Human Welfare. n. Cancer in PLANra For some years Dr. Erwin F. Smith, of the same Bureau of Plant Pathology, has been conducting some very remarkable experiments on cancer in plants. He believes, and it seems to be a very reasonable probability, that he has discovered the germ which produces can- cer in plants — the Bacillus tum^aciens. By injecting a httle of this germ in solution by a hypodermic syringe at different points in the leaf or stem he apparently can produce at will the various forms of cancer. That one single germ can cause not only cancer proper, but sarcoma and other forms of mahgnant disease, is a wholly new idea. It must be thoroughly tested by many others before it can be defin- itely accepted. It seems to be fairly true in plants, but whether true in animals and man is as yet not proved. A visit to his greenhouses in 153 MEDICAL RESEARCH AND HUMAN WELFARE Washington, which I enjoyed not long since, was a revelation. This remaricable discovery, if confirmed by others, will throw a wholly new light on the cancer problem. I have already called atten- tion to the solidarity and similarity of life in himians, animals, and plants. So far we have been unable to discover the cause of cancer in man and animals. This discovery by Dr. Smith, of a mode of producing cancer of all kinds at will in plants by a simple bacterial inoculation, makes one suspect that cancer in man and animals may also be of bacterial origin. It will give a new impetus to the search for such a germ. That it may prove successful will be the devout wish of every lover of his kind. in. Bacteeu in Rocks — Ibon Bactebia It is another very startling fact that bac- teria are found not only in the soil, but in rocks and in the ocean. Were the earth and the ocean devoid of bacteria, the world "would soon be uninhabitable to plants and animals." "They were the soil-forming and the soil-nour- ishing agents of the primal earth" is the strik- ing testimony of Henry Fairfield Osbom. The 154 BACTERIA IN ROCES great majority of bacteria are "good bacteria." They assist not only in the fixation of nitrogen, but in breaking up the rocks into fertile soU. In the disintegrating rocks of Alpine summits where no other life existed, Muntz found the rocks swarming with nitrifying bacteria. In 1915 Walcott discovered some fossil bacteria in rocks, the age of which he estimated at 33,000,000 years. (Plate HI, Fig. 3.) Such bacteria not only astonish us by their enter- prising precocity, but challenge our admiration as the most conspicuous instance of prolonged, modest "watchful waiting" to be discovered on record. The massive limestones of the Tetons are believed to be the product of the algal flora and the calcareous bacteria. One imusual kind of bacteria are known as "iron bacteria." In sixty-one samples of fer- ruginous stones from different parts of the world Molisch found bacteria in fifty-seven and suspected their presence in the other four. These bacteria become impregnated with the iron compounds in the water, and, dying, leave the iron as a legacy. In iron springs and bogs the iron thus deposited or secreted is believed to be the source of the so-called "bog iron ore." But what has all this to do with Medical 155 MEDICAL RESEARCH AND HUMAN WELFARE Research? you ask. The reply is self-evident. We owe to these humble, microscopic, Uving things the origin on the earth of a suitable soil for plants and the fixation of the nitrogen of the air in its various combinations. In the primal world the only nitrogen in existence was the free nitrogen of the air. All the nitrogen compounds in existence and therefore all our vegetable and ultimately our animal foodstuffs have resulted from the abiUty of the bacteria to fix the free nitrogen of the air. Had it not been for the researches I have so inadequately described we should not have recognized even the existence of any bacteria. Their great importance is not confined to med- icine. Theirs is a world-wide, age-long r61e of supreme importance to the welfare of the en- tire human race. What would be our condition to-day if the progress due to Medical Research were sud- denly annihilated; if we knew nothing of the bacterial origin of so many diseases, if we were ignorant of the means of preventing them, and were relegated to the atrocities of smallpox, cholera, the black death, and yellow fever? If typhus and typhoid and diphtheria were allowed to run riot as of yore? And who have 156 BACTERIA IN ROCKS ever been the advance guard in the war against disease? My own profession, I proudly reply. What foes have they not faced — diphtheria, plague, sleeping-sickness, typhus, cholera, yel- low fever, all these and more. And scores have made the supreme sacrifice. CONCLUSION What now is the conclusion of the whole matter? What a serried array of nearly threescore topics I have brought before you in rapid suc- cession! Every disease named has witnessed, during my own professional lifetime, a notable mitigation of its ravages or even its actual or prospective total annihilation. Yet I have had to omit far more than I have included. Even with these omissions I fear I have wearied you with the long recital. The warfare of Medical Research on Disease has been most successful. Let me recall only a few of the victories gained : in some, practically complete victories; in others, less complete victories, due largely to neglect of the lessons and maxims of Research: — Yellow fever Diphtheria Typhoid fever Puerperal fever Typhus fever Tuberculosia Tetanus Malta fever Malaria Anthrax and other diseases of animals If to these we add the blessings of Anes- thesia and the enormous progress in modem 158 CONCLUSION surgery as a result of Bacteriology and Anti- sepsis, do you wonder that I glow with enthu- siasm at what my profession has done for Humanity during one single lifetime? In these fruitful years Medical Research has done more for Human Welfare than in all the centuries since Time began! When the Great Peace shall follow the Great War, one conflict will not stop. The war of our guild against Disease — as old and as eternal as the war between Ormuzd and Ahriman, be- tween Good and Evil — will never cease until the last disease has been conquered and Hu- manity has been set free. In my Jefferson clinic, before I began any operation, my house surgeon always read the history of the case. He recited the name, age, occupation, etc., followed nearly always by this one phrase — "Had the usual diseases of childhood! " At least once a year I interrupted the reading and said to my class, "It is mon- strous that childhood should have any 'usual diseases.' Before long I pray God, and you may live to see that joyous day, when our case-histories will read, "Had the usual health of childhood." Research, Research, Reseakch — that is the 159 CONCLUSION method by which we shall enter into the Para- dise of Health, and not for childhood only, but a lifelong Paradise, till Death shall come, not as our last enemy, but as our best friend, to open to us the gates of Immortality.^ 1 [Even since these Lectures were delivered new discoveries have been made. The paraffin treatment of burns has been investigated very actively by many surgeons in Europe and America. The happy result is that our present means of treatment of burns is enor- mously better than it has ever been before. Drs. C. G. Bull and Ida W. Pritchett, of the Rockefeller Insti- tute, published in July, 1917, their discovery of the germ of gas gangrene and also of an antitoxin as a remedy. This antitoxin had proved so successful on animals, that later it was used in some of the very rare cases of the same disease in this country and its value to man was confirmed. It is now beitag tested on a large scale in the war zone in France with the prospect of con- quering one of the greatest foes of the wounded soldiers, — a victory comparable only with those over tetanus and typhoid fever. In addition to this, it is probable that the germ of trench fever has been discovered by Dimond. It is probably a low form of animal life. It is carried, like the plague, by the rat flea. As the trenches are alive with rats its dissemination is easy. These facts (and there are many other important researches) show how constantly active Medical Research has been in the midst of war, and how all its discoveries have tended to mitigate suffering and conserve human life.] THE ]QND CAMBRIDGE . MASSACHUSETTS D • S . A