(*) Osler wrote a preface for the 1911 English edition of the Life by Vallery-Radot.--Ed.

At the middle of the last century we did not know much more of the actual causes of the great scourges of the race, the plagues, the fevers and the pestilences, than did the Greeks. Here comes Pasteur's great work. Before him Egyptian darkness; with his advent a light that brightens more and more as the years give us ever fuller knowledge. The facts that fevers were catching, that epidemics spread, that infection could remain attached to articles of clothing, etc., all gave support to the view that the actual cause was something alive, a contagium vivum.

It was really a very old view, the germs of which may be found in the Fathers, but which was first clearly expressed--so far as I know--by Fracastorius, the Veronese physician, in the sixteenth century, who spoke of the seeds of contagion pa.s.sing from one person to another;(12) and he first drew a parallel between the processes of contagion and the fermentation of wine. This was more than one hundred years before Kircher, Leeuwenhoek and others began to use the microscope and to see animalcula, etc., in water, and so give a basis for the "infinitely little" view of the nature of disease germs. And it was a study of the processes of fermentation that led Pasteur to the sure ground on which we now stand.

(12) Varro, in De Re Rustica, Bk. I, 12 (circa 40 B.C.), speaks of minute organisms which the eye cannot see and which enter the body and cause disease.

Out of these researches arose a famous battle which kept Pasteur hard at work for four or five years--the struggle over spontaneous generation.

It was an old warfare, but the microscope had revealed a new world, and the experiments on fermentation had lent great weight to the omne vivum ex ovo doctrine. The famous Italians, Redi and Spallanzani, had led the way in their experiments, and the latter had reached the conclusion that there is no vegetable and no animal that has not its own germ. But heterogenesis became the burning question, and Pouchet in France, and Bastian in England, led the opposition to Pasteur. The many famous experiments carried conviction to the minds of scientific men, and destroyed forever the old belief in spontaneous generation. All along, the a.n.a.logy between disease and fermentation must have been in Pasteur's mind; and then came the suggestion, "What would be most desirable is to push those studies far enough to prepare the road for a serious research into the origin of various diseases." If the changes in lactic, alcoholic and butyric fermentations are due to minute living organisms, why should not the same tiny creatures make the changes which occur in the body in the putrid and suppurative diseases? With an accurate training as a chemist, having been diverted in his studies upon fermentation into the realm of biology, and nourishing a strong conviction of the ident.i.ty between putrefactive changes of the body and fermentation, Pasteur was well prepared to undertake investigations which had hitherto been confined to physicians alone.

So impressed was he with the a.n.a.logy between fermentation and the infectious diseases that, in 1863, he a.s.sured the French Emperor of his ambition "to arrive at the knowledge of the causes of putrid and contagious diseases." After a study upon the diseases of wines, which has had most important practical bearings, an opportunity arose which changed the whole course of his career, and profoundly influenced the development of medical science. A disease of the silkworm had, for some years, ruined one of the most important industries in France, and in 1865 the Government asked Pasteur to give up his laboratory work and teaching, and to devote his whole energies to the task of investigating it. The story of the brilliant success which followed years of application to the problem will be read with deep interest by every student of science. It was the first of his victories in the application of the experimental methods of a trained chemist to the problems of biology, and it placed his name high in the group of the most ill.u.s.trious benefactors of practical industries.

In a series of studies on the diseases of beer, and on the mode of production of vinegar, he became more and more convinced that these studies on fermentation had given him the key to the nature of the infectious diseases. It is a remarkable fact that the distinguished English philosopher of the seventeenth century, the man who more than anyone else of his century appreciated the importance of the experimental method, Robert Boyle, had said that he who could discover the nature of ferments and fermentation, would be more capable than anyone else of explaining the nature of certain diseases.

In 1876 there appeared in Cohn's "Beitrage zur Morphologie der Pflanzen"

(II, 277-310), a paper on the "AEtiology of Anthrax" by a German district physician in Wollstein, Robert Koch, which is memorable in our literature as the starting point of a new method of research into the causation of infectious diseases. Koch demonstrated the constant presence of germs in the blood of animals dying from the disease. Years before, those organisms had been seen by Pollender and Davaine, but the epoch-making advance of Koch was to grow those organisms in a pure culture outside the body, and to produce the disease artificially by inoculating animals with the cultures Koch is really our medical Galileo, who, by means of a new technique,--pure cultures and isolated staining,--introduced us to a new world. In 1878, followed his study on the "AEtiology of Wound Infections," in which he was able to demonstrate conclusively the a.s.sociation of micro-organisms with the disease. Upon those two memorable researches made by a country doctor rests the modern science of bacteriology.

The next great advance was the discovery by Pasteur of the possibility of so attenuating, or weakening, the poison that an animal inoculated had a slight attack, recovered and was then protected against the disease. More than eighty years had pa.s.sed since on May 14, 1796, Jenner had vaccinated a child with cowpox and proved that a slight attack of one disease protected the body from a disease of an allied nature. An occasion equally famous in the history of medicine was a day in 1881, when Pasteur determined that a flock of sheep vaccinated with the attenuated virus of anthrax remained well, when every one of the unvaccinated infected from the same material had died. Meanwhile, from Pasteur's researches on fermentation and spontaneous generation, a transformation had been initiated in the practice of surgery, which, it is not too much to say, has proved one of the greatest boons ever conferred upon humanity. It had long been recognized that, now and again, a wound healed without the formation of pus, that is, without suppuration, but both spontaneous and operative wounds were almost invariably a.s.sociated with that process; and, moreover, they frequently became putrid, as it was then called,--infected, as we should say,--the general system became involved and the patient died of blood poisoning.

So common was this, particularly in old, ill-equipped hospitals, that many surgeons feared to operate, and the general mortality in all surgical cases was very high. Believing that it was from outside that the germs came which caused the decomposition of wounds, just as from the atmosphere the sugar solution got the germs which caused the fermentation, a young surgeon in Glasgow, Joseph Lister, applied the principles of Pasteur's experiments to their treatment. From Lister's original paper(*) I quote the following: "Turning now to the question how the atmosphere produces decomposition of organic substances, we find that a flood of light has been thrown upon this most important subject by the philosophic researches of M. Pasteur, who has demonstrated by thoroughly convincing evidence that it is not to its oxygen or to any of its gaseous const.i.tuents that the air owes this property, but to minute particles suspended in it, which are the germs of various low forms of life, long since revealed by the microscope, and regarded as merely accidental concomitants of putrescence, but now shown by Pasteur to be its essential cause, resolving the complex organic compounds into substances of simpler chemical const.i.tution, just as the yeast-plant converts sugar into alcohol and carbonic acid." From these beginnings modern surgery took its rise, and the whole subject of wound infection, not only in relation to surgical diseases, but to child-bed fever, forms now one of the most brilliant chapters in the history of preventive medicine.

(*) Lancet, March 16, 1867. (Cf. Camac: Epoch-making Contributions, etc., 1909, p. 7.--Ed.)

With the new technique and experimental methods, the discovery of the specific germs of many of the more important acute infections followed each other with bewildering rapidity: typhoid fever, diphtheria, cholera, teta.n.u.s, plague, pneumonia, gonorrhoea and, most important of all, tuberculosis. It is not too much to say that the demonstration by Koch of the "bacillus tuberculosis" (1882) is, in its far-reaching results, one of the most momentous discoveries ever made.

Of almost equal value have been the researches upon the protozoan forms of animal life, as causes of disease. As early as 1873, spirilla were demonstrated in relapsing fever. Laveran proved the a.s.sociation of haematozoa with malaria in 1880. In the same year, Griffith Evans discovered trypanosomes in a disease of horses and cattle in India, and the same type of parasite was found in the sleeping sickness. Amoebae were demonstrated in one form of dysentery, and in other tropical diseases protozoa were discovered, so that we were really prepared for the announcement in 1905, by Schaudinn, of the discovery of a protozoan parasite in syphilis. Just fifty years had pa.s.sed since Pasteur had sent in his paper on "Lactic Acid Fermentation" to the Lille Scientific Society--half a century in which more had been done to determine the true nature of disease than in all the time that had pa.s.sed since Hippocrates. Celsus makes the oft-quoted remark that to determine the cause of a disease often leads to the remedy,(*) and it is the possibility of removing the cause that gives such importance to the new researches on disease.

(*) "Et causae quoque estimatio saepe morb.u.m solvit," Celsus, Lib. I, Prefatio.--Ed.

INTERNAL SECRETIONS

ONE of the greatest contributions of the nineteenth century to scientific medicine was the discovery of the internal secretions of organs. The basic work on the subject was done by Claude Bernard, a pupil of the great Magendie, whose saying it is well to remember--"When entering a laboratory one should leave theories in the cloakroom." More than any other man of his generation, Claude Bernard appreciated the importance of experiment in practical medicine. For him the experimental physician was the physician of the future--a view well borne out by the influence his epoch-making work has had on the treatment of disease. His studies on the glycogenic functions of the liver opened the way for the modern fruitful researches on the internal secretions of the various glands. About the same time that Bernard was developing the laboratory side of the problem, Addison, a physician to Guy's Hospital, in 1855, pointed out the relation of a remarkable group of symptoms to disease of the suprarenal glands, small bodies situated above the kidneys, the importance of which had not been previously recognized. With the loss of the function of these glands by disease, the body was deprived of something formed by them which was essential to its proper working.

Then, in the last third of the century, came in rapid succession the demonstration of the relations of the pancreas to diabetes, of the vital importance of the thyroid gland and of the pituitary body. Perhaps no more striking ill.u.s.tration of the value of experimental medicine has ever been given than that afforded by the studies upon those glands.

The thyroid body, situated in the neck and the enlargement of which is called goitre, secretes substances which pa.s.s into the blood, and which are necessary for the growth of the body in childhood, for the development of the mind and for the nutrition of the tissues of the skin. If, following an infectious disease, a child has wasting of this gland, or if, living in a certain district, it has a large goitre, normal development does not take place, and the child does not grow in mind or body and becomes what is called a cretin. More than this--if in adult life the gland is completely removed, or if it wastes, a somewhat similar condition is produced, and the patient in time loses his mental powers and becomes fat and flabby--myxedematous. It has been shown experimentally in various ways that the necessary elements of the secretion can be furnished by feeding with the gland or its extracts, and that the cretinoid or myxedematous conditions could thus be cured or prevented.

Experimental work has also demonstrated the functions of the suprarenal glands and explained the symptoms of Addison's disease, and chemists have even succeeded in making synthetically the active principle adrenalin.

There is perhaps no more fascinating story in the history of science than that of the discovery of these so-called ductless glands. Part of its special interest is due to the fact that clinicians, surgeons, experimental physiologists, pathologists and chemists have all combined in splendid teamwork to win the victory. No such miracles have ever before been wrought by physicians as those which we see in connection with the internal secretion of the thyroid gland. The myth of bringing the dead back to life has been a.s.sociated with the names of many great healers since the incident of Empedocles and Pantheia, but nowadays the dead in mind and the deformed in body may be restored by the touch of the magic wand of science. The study of the interaction of these internal secretions, their influence upon development, upon mental process and upon disorders of metabolism is likely to prove in the future of a benefit scarcely less remarkable than that which we have traced in the infectious diseases.

CHEMISTRY

IT is not making too strong a statement to say that the chemistry and chemical physics of the nineteenth century have revolutionized the world. It is difficult to realize that Liebig's famous Giessen laboratory, the first to be opened to students for practical study, was founded in the year 1825. Boyle, Cavendish, Priestley, Lavoisier, Black, Dalton and others had laid a broad foundation, and Young, Frauenhofer, Rumford, Davy, Joule, Faraday, Clerk-Maxwell, Helmholtz and others built upon that and gave us the new physics and made possible our age of electricity. New technique and new methods have given a powerful stimulus to the study of the chemical changes that take place in the body, which, only a few years ago, were matters largely of speculation.

"Now," in the words of Professor Lee, "we recognize that, with its living and its non-living substances inextricably intermingled, the body const.i.tutes an intensive chemical laboratory in which there is ever occurring a vast congeries of chemical reactions; both constructive and destructive processes go on; new protoplasm takes the place of old. We can a.n.a.lyze the income of the body and we can a.n.a.lyze its output, and from these data we can learn much concerning the body's chemistry. A great improvement in the method of such work has recently been secured by the device of inclosing the person who is the subject of the experiment in a respiration calorimeter. This is an air-tight chamber, artificially supplied with a constant stream of pure air, and from which the expired air, laden with the products of respiration, is withdrawn for purposes of a.n.a.lysis. The subject may remain in the chamber for days, the composition of all food and all excrete being determined, and all heat that is given off being measured. Favorable conditions are thus established for an exact study of many problems of nutrition. The difficulties increase when we attempt to trace the successive steps in the corporeal pathway of molecule and atom. Yet these secrets of the vital process are also gradually being revealed. When we remember that it is in this very field of nutrition that there exist great popular ignorance and a special p.r.o.neness to fad and prejudice, we realize how practically helpful are such exact studies of metabolism."(13)

(13) Frederick S. Lee, Ph.D.: Scientific Features of Modern Medicine, New York, 1911. I would like to call attention to this work of Professor Lee's as presenting all the scientific features of modern medicine in a way admirably adapted for anyone, lay or medical, who wishes to get a clear sketch of them.

CHAPTER VI -- THE RISE OF PREVENTIVE MEDICINE

THE story so far has been of men and of movements--of men who have, consciously or unconsciously, initiated great movements, and of movements by which, nolens volens, the men of the time were moulded and controlled. Hippocrates, in the tractate on "Ancient Medicine," has a splendid paragraph on the att.i.tude of mind towards the men of the past.

My attention was called to it one day in the Roman Forum by Commendatore Boni, who quoted it as one of the great sayings of antiquity. Here it is: "But on that account, I say, we ought not to reject the ancient Art, as if it were not, and had not been properly founded, because it did not attain accuracy in all things, but rather, since it is capable of reaching to the greatest exact.i.tude by reasoning, to receive it and admire its discoveries, made from a state of great ignorance, and as having been well and properly made, and not from chance."(1)

(1) The Works of Hippocrates, Adams, Vol. I, p. 168, London, 1849 (Sydenham Society).

I have tried to tell you what the best of these men in successive ages knew, to show you their point of outlook on the things that interest us. To understand the old writers one must see as they saw, feel as they felt, believe as they believed--and this is hard, indeed impossible! We may get near them by asking the Spirit of the Age in which they lived to enter in and dwell with us, but it does not always come. Literary criticism is not literary history--we have no use here for the former, but to a.n.a.lyze his writings is to get as far as we can behind the doors of a man's mind, to know and appraise his knowledge, not from our standpoint, but from that of his contemporaries, his predecessors and his immediate successors. Each generation has its own problems to face, looks at truth from a special focus and does not see quite the same outlines as any other. For example, men of the present generation grow up under influences very different from those which surrounded my generation in the seventies of the last century, when Virchow and his great contemporaries laid the sure and deep foundations of modern pathology. Which of you now knows the "Cellular Pathology" as we did? To many of you it is a closed book,--to many more Virchow may be thought a spent force. But no, he has only taken his place in a great galaxy. We do not forget the magnitude of his labors, but a new generation has new problems--his message was not for you--but that medicine today runs in larger moulds and turns out finer castings is due to his life and work.

It is one of the values of lectures on the history of medicine to keep alive the good influences of great men even after their positive teaching is antiquated. Let no man be so foolish as to think that he has exhausted any subject for his generation. Virchow was not happy when he saw the young men pour into the old bottle of cellular pathology the new wine of bacteriology. Lister could never understand how aseptic surgery arose out of his work. Ehrlich would not recognize his epoch-making views on immunity when this generation has finished with them. I believe it was Hegel who said that progress is a series of negations--the denial today of what was accepted yesterday, the contradiction by each generation of some part at least of the philosophy of the last; but all is not lost, the germ plasm remains, a nucleus of truth to be fertilized by men often ignorant even of the body from which it has come. Knowledge evolves, but in such a way that its possessors are never in sure possession. "It is because science is sure of nothing that it is always advancing" (Duclaux).

History is the biography of the mind of man, and its educational value is in direct proportion to the completeness of our study of the individuals through whom this mind has been manifested. I have tried to take you back to the beginnings of science, and to trace its gradual development, which is conditioned by three laws. In the first place, like a living organism, truth grows, and its gradual evolution may be traced from the tiny germ to the mature product. Never springing, Minerva-like, to full stature at once, truth may suffer all the hazards incident to generation and gestation. Much of history is a record of the mishaps of truths which have struggled to the birth, only to die or else to wither in premature decay. Or the germ may be dormant for centuries, awaiting the fullness of time.

Secondly, all scientific truth is conditioned by the state of knowledge at the time of its announcement. Thus, at the beginning of the seventeenth century, the science of optics and mechanical appliances had not made possible (so far as the human mind was concerned) the existence of blood capillaries and blood corpuscles. Jenner could not have added to his "Inquiry" a study on immunity; Sir William Perkin and the chemists made Koch technique possible; Pasteur gave the conditions that produced Lister; Davy and others furnished the preliminaries necessary for anaesthesia. Everywhere we find this filiation, one event following the other in orderly sequence--"Mind begets mind," as Harvey (De Generatione) says; "opinion is the source of opinion. Democritus with his atoms, and Eudoxus with his chief good which he placed in pleasure, impregnated Epicurus; the four elements of Empedocles, Aristotle; the doctrines of the ancient Thebans, Pythagoras and Plato; geometry, Euclid."(2)

(2) Works of William Harvey, translated by Robert Willis, London, 1847, p. 532.

And, thirdly, to scientific truth alone may the h.o.m.o mensura principle be applied, since of all mental treasures of the race it alone compels general acquiescence. That this general acquiescence, this aspect of certainty, is not reached per saltum, but is of slow, often of difficult growth,--marked by failures and frailties, but crowned at last with an acceptance accorded to no other product of mental activity,--is ill.u.s.trated by every important discovery from Copernicus to Darwin.

The difficulty is to get men to the thinking level which compels the application of scientific truths. Protagoras, that "mighty-wise man,"

as Socrates called him, who was responsible for the aphorism that man is the measure of all things, would have been the first to recognize the folly of this standard for the people at large. But we have gradually reached a stage in which knowledge is translated into action, made helpful for suffering humanity, just as the great discoveries in physics and chemistry have been made useful in the advance of civilization.

We have traced medicine through a series of upward steps--a primitive stage, in which it emerged from magic and religion into an empirical art, as seen among the Egyptians and Babylonians; a stage in which the natural character of disease was recognized and the importance of its study as a phenomenon of nature was announced; a stage in which the structure and functions of the human body were worked out; a stage in which the clinical and anatomical features of disease were determined; a stage in which the causes of disorders were profitably studied, and a final stage, into which we have just entered, the application of the knowledge for their prevention. Science has completely changed man's att.i.tude towards disease.

Take a recent concrete ill.u.s.tration. A couple of years ago in Philadelphia and in some other parts of the United States, a very peculiar disease appeared, characterized by a rash upon the skin and moderate fever, and a const.i.tutional disturbance proportionate to the extent and severity of the eruption. The malady first broke out in the members of a crew of a private yacht; then in the crews of other boats, and among persons living in the boarding-houses along the docks. It was the cause of a great deal of suffering and disability.

There were three courses open: to accept the disease as a visitation of G.o.d, a chastening affliction sent from above, and to call to aid the spiritual arm of the church. Except the "Peculiar People" few now take this view or adopt this practice. The Christian Scientist would probably deny the existence of the rash and of the fever, refuse to recognize the itching and get himself into harmony with the Infinite. Thirdly, the method of experimental medicine.

First, the conditions were studied under which the individual cases occurred. The only common factor seemed to be certain straw mattresses manufactured by four different firms, all of which obtained the straw from the same source.

The second point was to determine the relation of the straw to the rash.

One of the investigators exposed a bare arm and shoulder for an hour between two mattresses. Three people voluntarily slept on the mattresses for one night. Siftings from the straw were applied to the arm, under all of which circ.u.mstances the rash quickly developed, showing conclusively the relation of the straw to the disease.

Thirdly, siftings from the straw and mattresses which had been thoroughly disinfected failed to produce the rash.

And fourthly, careful inspection of the siftings of the straw disclosed living parasites, small mites, which when applied to the skin quickly produced the characteristic eruption.

SANITATION

WHEN the thoughtful historian gets far enough away from the nineteenth century to see it as a whole, no single feature will stand out with greater distinctness than the fulfilment of the prophecy of Descartes that we could be freed from an infinity of maladies both of body and mind if we had sufficient knowledge of their causes and of all the remedies with which nature has provided us. Sanitation takes its place among the great modern revolutions--political, social and intellectual.

Great Britain deserves the credit for the first practical recognition of the maxim salus populi suprema lex. In the middle and latter part of the century a remarkable group of men, Southwood Smith, Chadwick, Budd, Murchison, Simon, Acland, Buchanan, J.W. Russell and Benjamin Ward Richardson, put practical sanitation on a scientific basis. Even before the full demonstration of the germ theory, they had grasped the conception that the battle had to be fought against a living contagion which found in poverty, filth and wretched homes the conditions for its existence. One terrible disease was practically wiped out in twenty-five years of hard work. It is difficult to realize that within the memory of men now living, typhus fever was one of the great scourges of our large cities, and broke out in terrible epidemics--the most fatal of all to the medical profession. In the severe epidemic in Ireland in the forties of the last century, one fifth of all the doctors in the island died of typhus. A better idea of the new crusade, made possible by new knowledge, is to be had from a consideration of certain diseases against which the fight is in active progress.

Nothing ill.u.s.trates more clearly the interdependence of the sciences than the reciprocal impulse given to new researches in pathology and entomology by the discovery of the part played by insects in the transmission of disease. The flea, the louse, the bedbug, the house fly, the mosquito, the tick, have all within a few years taken their places as important transmitters of disease. The fly population may be taken as the sanitary index of a place. The discovery, too, that insects are porters of disease has led to a great extension of our knowledge of their life history. Early in the nineties, when Dr. Thayer and I were busy with the study of malaria in Baltimore, we began experiments on the possible transmission of the parasites, and a tramp, who had been a medical student, offered himself as a subject. Before we began, Dr.

Thayer sought information as to the varieties of mosquitoes known in America, but sought in vain: there had at that time been no systematic study. The fundamental study which set us on the track was a demonstration by Patrick Manson,(3) in 1879, of the a.s.sociation of filarian disease with the mosquito. Many observations had already been made, and were made subsequently, on the importance of insects as intermediary hosts in the animal parasites, but the first really great scientific demonstration of a widespread infection through insects was by Theobald Smith, now of Harvard University, in 1889, in a study of Texas fever of cattle.(4) I well remember the deep impression made upon me by his original communication, which in completeness, in accuracy of detail, in Harveian precision and in practical results remains one of the most brilliant pieces of experimental work ever undertaken. It is difficult to draw comparisons in pathology; but I think, if a census were taken among the world's workers on disease, the judgment to be based on the damage to health and direct mortality, the votes would be given to malaria as the greatest single destroyer of the human race.