An Introduction to the Study of Experimental Medicine

" Claude Bernard, Recherches experimentales sur lea fonctiona du nerf spinal. {Memoires prSsent^s par divers savants etrangers d VAcademie des sciences. Vol. X. 1851.) to perfect our methods of dissection, so as to follow the nervous anastomoses more precisely and to compare each anatomist's description with nature. This is what I did, and I found that the difference between the authors in question came from their not having assigned the same limits to the nerves. So anatomy, carried further, explained their anatomical dissension. I therefore refuse to acknowledge that science has a place for men who make criticism their specialty, as in letters and in the arts. To be really useful, criticism in every science must be done by men of science themselves, and by the most eminent masters.

Another somewhat frequent error consists in confusing the history of man with the history of some science. Theological and didactic evolution of experimental science is by no means expressed in the chronological history of the men concerned with it. We must nevertheless except the mathematical and astronomical sciences; but this cannot apply to the physico-chemical experimental sciences or to medicine in particular. Medicine was born of need, said Baglivi, that is to say, from the first time that anyone was ill, men went to his aid and sought to cure him. From its cradle, medicine has therefore been an applied science mixed with religion and with the feelings of sympathy that men experienced one for another. But did medicine as a science exist? Evidently not. Continuing through centuries as blind empiricism, it enriched itself, little by little and almost by chance, with observations and investigations in unrelated directions. Physiology, pathology and therapeutics developed as distinct sciences. That was the wrong road. Only to-day can we begin to see the conception of an experimental, scientific medicine in the fusion of these three in a single point of view.

The experimental point of view is a coronation of perfected science; for we must not deceive ourselves; true science exists only when man succeeds in accurately foreseeing the phenomena of nature and mastering them. Noting and classifying natural bodies and phenomena is not at all the equivalent of complete science. True science acts and explains its action or its power: that is its character, that is its aim. Let me amplify my idea. I have often heard physicians say that physiology or the explanation of vital phenomena in either the physiological or the pathological state is only a part of medicine, because' medicine is knowledge of diseases in general. I have similarly heard zoologists say that physiology, or the explana-

tion of vital phenomena in all their variety, is only a dismemberment or specialty of zoology, because zoology is knowledge of animals in general. Talking in the same v^ay, a geologist or a mineralogist might say that physics and chemistry are only dismemberments of geology or mineralogy, which include knowledge of the earth and of animals in general. Here are mistakes or at least misunderstandings which need to be explained. First of all, we must recognize that our divisions into sciences are not a part of nature; they exist only in the mind which, by reason of its infirmity, is forced to create categories of bodies and of phenomena, so as to understand them better by studying their characteristics or properties from special points of view. It follows that the same body may be studied mineralogically, physically, chemically, etc. ; but in nature there is really neither chemistry nor physics, nor zoology, nor physiology, nor pathology ; there are only bodies to be classified or phenomena to be known and mastered. JSTow the science that gives man means of analyzing and experimentally mastering phenomena is the furthest advanced. It must necessarily be the last established; that is no reason to consider it a dismemberment of earlier sciences. In this respect, physiology, which is the highest and most difficult science of living beings, cannot be regarded as a dismemberment of medicine or zoology, any more than physics or chemistry are dismemberments of geology or mineralogy. Physics and chemistry are the two active mineral sciences by means of which man can master the phenomena of inorganic bodies. Physiology is the vital, active science by whose aid man will be able to act on animals and on man, whether in health or in sickness.

It would be a grave illusion for physicians to believe they know diseases by giving them names, because they classify and describe them, just as it would be an illusion for zoologists or botanists to believe they know animals and vegetables because they have named them, catalogued, dissected and shut them up in museums, after stuffing, preparing or drying them. Physicians will not know diseases until they can act on them rationally and experimentally, just as zoologists will not know animals until they explain and regulate the phenomena of life. To sum up, we must not be duped by our own works; we cannot assign any absolute value to scientific classifications, either in books or in academies. Men who leave the beaten track are innovators, and those who blindly persist in it hamper scientific progress. The very evolution of

human knowledge means that experimental science must be the goal, and this evolution requires that earlier sciences of classification shall lose importance as the experimental sciences develop. The spirit of man follows a necessary and logical course in the search for scientific truth. It observes facts, compares them, deduces appropriate results which it controls by experiment, to rise to more and more general propositions and truths. In this advancing labor, a man of science must, of course, know and deal with his predecessors' work. But he must be thoroughly convinced that this work is merely a support from which to go farther, and that new scientific truths are not to be found in study of the past, but rather in studies made anew on nature, i.e., in the laboratory. Useful scientific literature, then, is preeminently the scientific literature of modem work which enables us to keep up with scientific progress; and even this must not be carried too far, lest it dry up the mind and stifle invention and scientific originality. But what use can we find in exhuming worm-eaten theories or observations made without proper means of investigation ? That may, of course, be helpful in learning the mistakes through which the human mind has passed in its evolution, but it is time wasted for science, properly speaking. I deem it highly important to guide the minds of students early toward active experimental science, by making them understand that it develops in laboratories, instead of leaving them to believe that it awaits them in books or in the interpretation of ancient writings. We know from history the sterility of the scholastic path and that science did not begin to soar until men substituted for the authority of books the authority of facts ascertained in nature with the help of more and more perfect experimental methods ; Bacon's greatest merit was that he proclaimed this truth aloud.

As for me, I think that turning medicine back to-day toward the belated and aged commentaries of antiquity is a retrogression, a return to scholasticism, while guiding medicine toward laboratories and toward experimental, analytical study of disease is an advance along the path of true progress, that is, toward the foundation of experimental medical science. With me, this is a deep conviction; I shall always seek to make it prevail both in my teaching and in my work.

A physiological laboratory, therefore, should now be the culminating goal of any scientific physician's studies; but here again I must explain^ myself to avoid misunderstanding. Hospitals, or rather hospital wards, are not physicians' laboratories, as is often believed ; as we said before, these are only his fields for observation ; there must be held what we call clinics, i.e., studies of disease as complete as possible. Medicine necessarily begins with clinics, since they determine and define the object of medicine, i.e., the medical problem; but while they are the physician's first study, clinics are not the foundation of scientific medicine ; physiology is the foundation of scientific medicine because it must yield the explanation of morbid phenomena by showing their relations to the normal state. We shall never have a science of medicine as long as we separate the explanation of pathological from the explanation of normal, vital phenomena.

Here then lies the real medical problem; this is the foundation on which modem scientific medicine will be built. As we see, experimental medicine does not exclude clinical medicine; on the contrary, it comes only after it. But it is a higher science, and one necessarily more vast and general. We easily imagine how an observational or empirical physician, never leaving his hospital, may think medicine completely shut in there, as a science distinct from physiology, of which it feels no need. But for a man of science there is no separate science of medicine or physiology, there is only a science of life. There are only phenomena of life to be explained in the pathological as well as in the physiological state. By putting this fundamental idea and this general conception of medicine into the minds of young people at the outset of their medical studies, we shall show them that the physico-chemical sciences which they have learned are tools to help them analyze the phenomena of life in its normal and pathological states. In frequenting hospitals, amphitheatres and laboratories, they will easily grasp the general connection uniting all the medical sciences, instead of learning them like fragments of detached knowledge with no relation between them.

In a word, I consider hospitals only as the entrance to scientific medicine; they are the first field of observation which a physician enters ; but the true sanctuary of medical science is a laboratory ; only there can he seek explanations of life in the normal and pathological states by means of experimental analysis. I shall not concern myself here with the clinical side of medicine ; I assume it as known or as still being perfected in hospitals by the new methods of diagnosis which physics and chemistry are constantly giving to

symptomatology. In my opinion, medicine does not end in hospitals, as is often believed, but merely begins there. In leaving the hospital, a physician, jealous of the title in its scientific sense, must go into his laboratory; and there, by experiments on animals, he will seek to account for what he has observed in his patients, whether about the action of drugs or about the origin of morbid lesions in organs or tissues. There, in a word, he will achieve true medical science. Every scientific physician should, therefore, have a physiological laboratory; and this work is especially intended to give physicians rules and principles of experimentation to guide their study of experimental medicine, that is, their analytic and experimental study of disease. The principles of experimental medicine, then, will be simply the principles of experimental analysis applied to the phenomena of life in its healthy and its morbid states.

The biological sciences to-day are no longer seeking their path. Because of their complex nature they vacillated longer than other simpler sciences in the regions of philosophy and system; but they launched at last into the experimental path where to-day they are well advanced. So they now need only one thing more, and that is means of development. Such means are laboratories and all the conditions and instruments necessary to cultivate the scientific field of biology.

To the honor of French science, it must be stated that it had the glory of decisively inaugurating the experimental method in the science of vital phenomena. Toward the end of the last century, the renewal of chemistry strongly influenced the advance of physiological science, and the work of Lavoisier and Laplace on breathing cleared a fertile path for analytic physico-chemical experimentation on the phenomena of life. My teacher, Magendie, who was led into a medical career by this same influence, devoted his life to advocating experimentation in the study of physiological phenomena. ^Nevertheless, application of the experimental method to animals was hindered from the first by the lack of suitable laboratories and by all sorts of difficulties which are disappearing to-day, but from which I myself often suffered in my youth. The scientific impulse, started in France, spread through Europe, and little by little the analytic experimental method entered the realm of biological science as a general method of investigation. But this method was perfected more, and it brought forth more fruit in countries where conditions

for its development were more favorable. Throughout Germany- to-day there are laboratories, called physiological institutes, which are admirably endowed and organized for the experimental study of vital phenomena. They exist in Russia also, where new ones of gigantic size are being built. Scientific production is naturally in proportion to the means of cultivation which a science possesses; there is nothing astonishing, then, in the fact that Germany, where the means of cultivating the physiological sciences are most liberally installed, is distancing other countries in the quantity of its scientific production. The genius of man, of course, cannot abdicate its supremacy in science. In experimental science, however, a scientific man is the prisoner of his ideas^ if he does not learn to question nature for himself, and if he does not possess suitable and necessary tools. We cannot imagine a physicist or a chemist without his laboratory. But as for the physician, we are not yet in the habit of believing that he needs a laboratory; we think that hospitals and books should suffice. That is a mistake; clinical information no more suffices for physicians than knowledge of minerals suffices for chemists or physicists. Physiological physicians must experimentally analyze the phenomena of living matter, as physicists and chemists experimentally analyze the phenomena of inorganic matter. A laboratory is therefore a condition sine qua non of the development of experimental medicine, as it was for all the other physico-chemical sciences. Without it, neither experimenters nor experimental science can exist.

I shall no longer dwell on so important a subject which cannot here be sufficiently worked out ; let me end by saying that one truth is well established in modern science, namely, that scientific courses can only serve to introduce and to create a taste for the sciences. By pointing out, from a professional chair, the results as well as the methods of a science, a teacher may form the minds of his hearers and make them apt in learning and choosing their own direction ; but he can never make them men of science. The laboratory is the real nursery of true experimental scientists, i.e., those who create the science that others afterward popularize. N^ow if we want much fruit, we must first care for our nurseries of fruit trees. The evidence of this truth will necessarily bring about general and deep reform in scientific teaching. For, I repeat, it is to-day everywhere recognized that pure science germinates and develops in

laboratories, to spread out later and cover the world with useful applications. We must, therefore, first of all attend to the scientific source, since applied science necessarily proceeds from pure science. Science and men of science are cosmopolitans, and it seems hardly important whether a scientific truth develops at any particular spot on the globe, as long as the general diffusion of science allows all men to share in it. However I cannot help praying that my country, the evident promoter and protector of scientific progress and the starting point of the brilliant era through which experimental physical science is now passing, may have great, public, physiological laboratories as soon as possible, so as to make pleiads of physiologists and young experimenting physicians. Only laboratories can teach the difficulties of science to those who frequent them ; they show that pure science has always been the source of all the riches acquired by man and of all his real conquests over the phenomena of nature. This is also excellent education for the young, because it makes them understand that the present, very brilliant applications of science are merely the blossoming of earlier labors, and that those who reap the benefits to-day owe a tribute of gratitude to their predecessors who painfully cultivated the tree of science, but never saw its fruits.

I cannot here treat all the conditions necessary to a good laboratory of physiology or experimental medicine. That would obviously amount to summarizing everything still to be explained in this work. I shall therefore limit myself to adding one word. I said above, that the laboratory of a physiological physician must be the most complex of all laboratories, because the experimental analyses to be made there are the most complex of all, requiring the help of all other sciences. The laboratory of a medical physiologist must be connected with a hospital so as to receive the various pathological specimens on which scientific investigation is brought to bear. It \nust next include healthy and diseased animals for the study of questions of normal and pathological physiology. But as vital phenomena, whether in the normal or in the pathological state, are

^ In 1771 a course in experimental physiology was given by Professor A. Portal at the College de France; the experiments were reported by Monsieur Collomb who published them in letter form in 1771; they were republished in 1808 with a few additions in the work by Portal entitled: M^moires sur la nature et le traitem&nt de plusieu/rs maladies, aveo le precis d'expSriences stur les animaux vivanis. Paris, 1800-1825. analyzed mainly by means of tools borrowed from physico-chemical science, instruments must necessarily be somewhat liberally provided. The solution of certain scientific questions often imperatively demands costly and complicated instruments, so that we may then say that scientific questions are secondary to the question of money. However, I do not approve the luxury as to instruments to which certain physiologists have yielded. In my opinion, we should seek to simplify instruments as much as possible, not only for pecuniary, but also for scientific reasons ; for we need to learn that the more complicated the instrument, the more sources of error does it create. Experimenters do not grow great by the number and complexity of instruments ; it is really the other way. The great experimenters, Berzelius and Spallanzani, made great discoveries by means of simple instruments. In the course of this work, our principle, then, will be to seek, as far as possible, to simplify means of study ; for instruments must be allies not sources of error because of their complications.

The ideas explained in the first two parts of this introduction will be all the better understood if we can connect them with actual investigations in experimental physiology and medicine. For this reason, I have put together in the following part a certain number of examples that seem to me appropriate. As far as possible, I have quoted from myself in all these examples, for the sole reason that, in the matter of reasoning and intellectual processes, I shall be much more certain of what I describe in telling what has happened to me than in interpreting what may have taken place in the minds of others. I am not, however, so fatuous as to give these examples as models to follow; I use them only to express my ideas better and to make my thought easier to grasp.

In scientific investigations, various circumstances may serve as starting points for research ; I will reduce all these varieties, however, to two chief types: 1. Where the starting point for experimental research is an observation ; 2. Where the starting point for experimental research is an hypothesis or a theory. Experimental ideas are often born by chance, with the help of some casual observation. Nothing is more common ; and this is really the simplest way of beginning a piece of scientific work. We take a walk, so to speak, in the realm of science, and we pursue

what happens to present itself to our eyes. Bacon compares scientific investigation with hunting; the observations that present themselves are the game. Keeping the same simile, we may add that, if the game presents itself when we are looking for it, it may also present itself when we are not looking for it, or when we are looking for game of another kind. I shall cite an example in which these two cases presented themselves in succession. At the same time I shall be careful to analyze every circumstance involved, so as to show how the principles apply which we explained in the first part of the introduction and especially in Chapters I and II.

First example. — One day, rabbits from the market were brought into my laboratory. They were put on the table where they urinated, and I happened to observe that their urine was clear and acid. This fact struck me, because rabbits, which are herbivora, generally have turbid and alkaline urine; while on the other hand carnivora, as we know, have clear and acid urine. This observation of acidity in the rabbits' urine gave me an idea that these animals must be in the nutritional condition of carnivora. I assumed that they had probably not eaten for a long time, and that they had been transformed by fasting, into veritable carnivorous animals, living on their own blood. ^Nothing was easier than to verify this preconceived idea or hypothesis by experiment. I gave the rabbits grass to eat ; and a few hours later, their urine became turbid and alkaline. I then subjected them to fasting and after twenty-four hours or thirty-six hours at most, their urine again became clear and strongly acid ; then after eating grass, their urine became alkaline again, etc. I repeated this very simple experiment a great many times, and always with the same result. I then repeated it on a horse, an herbivorous animal which also has turbid and alkaline urine. I found that fasting, as in rabbits, produced prompt acidity of the urine, with such an increase in urea, that it spontaneously crystallizes at times in the cooled urine. As a result of my experiments, I thus reached the general proposition which then was still unknown, to wit, that all fasting animals feed on meat, so that herbivora then have urine like that of carnivora.

We are here dealing with a very simple, particular fact which allows us easily to follow the evolution of experimental reasoning. When we see a phenomenon which we are not in the habit of seeing, we must always ask ourselves what it is connected with, or putting it differently, what is its proximate cause ; tlie answer or the idea, which presents itself to the mind, must then be submitted to experiment. When I saw the rabbits' acid urine, I instinctively asked myself what could be its cause. The experimental idea consisted in the connection, which my mind spontaneously made, between acidity of the rabbits' urine, and the state of fasting which I considered equivalent to a true flesh-eater's diet. The inductive reasoning which I implicitly went through was the following syllogism: the urine of carnivora is acid; now the rabbits before me have acid urine, therefore they are carnivora, i.e., fasting. This remained to be established by experiment.

But to prove that my fasting rabbits were really carnivorous, a counterproof was required. A carnivorous rabbit had to be experimentally produced by feeding it with meat, so as to see if its urine would then be clear, as it was during fasting. So I had rabbits fed on cold boiled beef (which they eat very nicely when they are given nothing else) . My expectation was again verified, and, as long as the animal diet was continued, the rabbits kept their clear and acid urine.

To complete my experiment, I made an autopsy on my animals, to see if meat was digested in the same way in rabbits as in carnivora. I found, in fact, all the phenomena of an excellent digestion in their intestinal reactions, and I noted that all the chyliferous vessels were gorged with very abundant white, milky chyle, just as in carnivora. But a propos of these autopsies which confirmed my ideas on meat digestion in rabbits, lo and behold a fact presented itself which I had not remotely thought of, but which became, as we shall see, my starting point in a new piece of work.

Second example. — (Sequel to the last) — In sacrificing the rabbits which I had fed on the meat, I happened to notice that the white and milky lymphatics were first visible in the small intestine at the lower part of the duodenum, about thirty centimeters below the pylorus. This fact caught my attention because in dogs they are first visible much higher in the duodenum just below the pylorus. On examining more closely, I noted that this peculiarity in rabbits coincided with the position of the pancreatic duct which was inserted very low and near the exact place where the lymphatics began to contain a chyle made white and milky by emulsion of fatty nutritive materials.

Chance observation of this fact evoked the idea which brought to birth the thought in my mind, that pancreatic juice might well cause the emulsion of fatty materials and consequently their absorption by the lymphatic vessels. Instinctively again, I made the following syllogism : the white chyle is due to emulsion of the fat ; now in rabbits white chyle is formed at the level where pancreatic juice is poured into the intestine ; therefore it is pancreatic juice that makes the emulsion of fat and forms the white chyle. This had to be decided by experiment.

In view of this preconceived idea I imagined and at once performed a suitable experiment to verify the truth or falsity of my suppositions. The experiment consisted in trying the properties of pancreatic juice directly on neutral fats. But pancreatic juice does not spontaneously flow outside of the body, like saliva, for instance, or urine; its secretory organ is, on the contrary, lodged deep in the abdominal cavity. I was therefore forced to use the method of experimentation to secure the pancreatic fluid from living animals in suitable physiological conditions and in sufficient quantity. Only then could I carry out my experiment, that is to say, control my preconceived idea ; and the experiment proved that my idea was correct. In fact pancreatic juice obtained in suitable conditions from dogs, rabbits and various other animals, and mixed with oil or melted fat, always instantly emulsified, and later split these fatty bodies into fatty acids, glycerine, etc., etc., by means of a specific ferment.

I shall not follow these experiments further, having explained them at length in a special work.^ I wish here to show merely how an accidental first observation of the acidity of rabbits' urine suggested to me the idea of making experiments on them with carnivorous feeding, and how later, in continuing these experiments, I brought to light, without seeing.it, another observation concerning the peculiar arrangement of the junction of the pancreatic duct in rabbits. This second observation gave me, in turn, the idea of experimenting on the behavior of pancreatic juice.

From the above examples we see how chance observation of a fact or phenomenon brings to birth, by anticipation, a preconceived idea or hypothesis about the probable cause of the phenomenon ob- * Claude Bernard, Memoire sur le pancreas et sur le role du sue pancr^atique dans les phenomenes digestifs. Paris, 1856. served ; how the preconceived idea begets reasoning which results in the experiment which verifies it; how, in one case, we had to have recourse to experimentation, i.e., to the use of more or less complicated operative processes, etc., to work out the verification. In the last example, experiment played a double role; it first judged and confirmed the provisions of the reasoning which it had begotten; but what is more, it produced a fresh observation. We may therefore call this observation an observation produced or begotten by experiment. This proves that, as we said, all the results of an experiment must be observed, both those connected with the preconceived idea and those without any relation to it. If we saw only facts connected with our preconceived idea, we should often cut ourselves off from making discoveries. For it often happens that an unsuccessful experiment may produce an excellent observation, as the following example will prove.