An Introduction to the Study of Experimental Medicine

and seeing the sick recover of themselves and without medicine, they were inclined to ask, not only whether the medicines given were useful, but whether they were not harmful. The first medical reflection, or first medical reasoning, resulting from study of the sick, made men recognize a spontaneous, medicinal force in the living organism ; and observation taught them to respect it and try merely to guide and help it in its fortunate tendencies. The first steps in scientific medicine taken by Hippocrates involved a doubt about the curative results of empirical methods and the appeal to the laws of living organisms to effect the cure of the sick. But this kind of medicine, founded as science on observation, and as treatment on expectancy, still allows other doubts to subsist. While recognizing how direful for the patient it may be to use empirical medicaments to disturb the tendencies of nature when they are favorable, men must have asked themselves, on the other hand, whether it might not be possible, and useful to the patient, to disturb and change them when they were bad. It was therefore no longer merely a case of physicians guiding and helping nature in its fortunate tendencies; Quo vergit natura, eo ducendum, but also of combating and dominating nature in its evil tendencies, medicus naturae superator. The heroic remedies, the universal panaceas, the specifics of Paracelsus and others, are merely the empirical expression of a reaction against Hippocratic medicine, i.e., against expectancy.

By its very nature, experimental medicine has no system and rejects nothing in the way of treatment or cure of disease; it believes and accepts everything that is founded on observation and proved by experience. Though we have repeated it often already, we must here recall the fact that experimental medicine, as it is called, is certainly not a new theory of medicine. It is one with the medicine of all people and times, in all its solid gains and sound observatioiis. Scientific, experimental medicine goes as far as possible in the study of vital phenomena; it cannot limit itself to observing diseases or content itself with expectancy or stop at remedies empirically given, but in addition it must study experimentally the mechanism of diseases and the action of remedies, so as to account for them scientifically. Above all, the analytic spirit of the experimental method in modem science must be brought into medicine; but this will not absolve experimental physicians from being good observers; they must be thoroughly educated in clinics,

must know diseases accurately in all their normal, abnormal and insidious forms, be familiar with every method of pathological investigation, and be good, as we say, in diagnosis and prognosis. Be- sides this, they must be consummate therapeutists and know everything that empirical or systematic attempts have taught us about the action of remedies in different diseases. In a word, experimental physicians, like all educated physicians, must have every kind of knowledge that we have just enumerated; but they will differ from systematic physicians in not conducting themselves according to any system; but, instead of taking as their goal observation of disease and notation of the action of remedies, they will be distinguished from Hippocratic and empirical physicians by their will to go further and, with the help of experimentation, enter into the explanation of vital mechanisms. For their part, Hippocratic physicians are satisfied when they succeed in clearly describing a disease in its course, in learning and foreseeing its various favorable or direful endings by exact signs, so as to be able to intervene, if necessary, to help nature and to guide it toward a happy ending ; scientific medicine, they believe, should set itself this goal. Empirical physicians are satisfied when, with the help of empiricism, they succeed in knowing that a given remedy cures a given disease, in learning the exact doses in which to administer it, and the cases in which it must be used ; they may also believe they have reached the limits of medical, science.

But while experimenting physicians are the first to admit and understand the scientific and practical importance of the preceding ideas, without which medicine could not exist, they do not believe that medicine as a science should stop at observation and empirical knowledge of phenomena or be satisfied with somewhat vague systems. So that Hippocratic, empirical and experimenting physicians do not differ in the least in the nature of their knowledge ; they differ only in the mental point of view which leads them to carry the medical problem somewhat further. The mediating power of nature invoked by Hippocratists, and the therapeutic or other force assumed by empiricists are simple hypotheses in the eyes of experimenting physicians. With the help of experimentation, they must penetrate into the inmost phenomena of living machines and define their mechanism in its normal as well as its pathological state. We must investigate the immediate causes of normal phenomena, which should be found in definite organic conditions in

relation to the properties of fluids and tissues. It is not enough to know the phenomena of mineral nature empirically as well as their results; but physicists and chemists mean to go back to their necessary conditions, i.e., to their immediate causes, so as to be able to regulate their manifestation. In the same way, it is not enough for physiologists to know empirically the normal and abnormal phenomena of living nature ; but like physicists and chemists, they mean to go back to the immediate causes of phenomena, i.e., to their necessary conditions. In a word, it is not enough for experimenting physicians to know that quinine cures fever ; but what is above all significant to them is knowing what fever is and accounting for the mechanism by which quinine cures. All this is significant to experimenting physicians because, as soon as they know it, the fact of curing fever with quinine will no longer be an. empirical, isolated fact, but a scientific fact. This fact will then connect itself with conditions which will relate it to other phenomena, and we shall thus be led to knowledge of the laws of organisms and the possibility of regulating their manifestations. Experimental physiciajis are therefore concerned most of all with seeking to establish medical science on the same principles as all the other experimental sciences. Let us now see how a man animated with this scientific spirit should behave at a patient's bedside.

Hippocratists, believing in a mediating nature, and but little in the curative effect of drugs, quietly follow the course of a disease; in almost passive expectancy, they limit themselves to encouraging the fortunate tendencies of nature with a few simple medicines. Empiricists, with their faith in the efficacy of drugs as a means of changing the direction of diseases and curing them, content themselves with empirically noting medicinal effects, without trying to understand their mechanism scientifically. They are never perplexed : when one remedy fails, they try another ; they always have receipts or formulae at hand for any and every case, because they draw on an immense therapeutic arsenal. Empirical medicine is certainly the most popular. People believe that through a kind of compensation nature provides a remedy for every ill, and that medicine consists in a collection of recipes for all ills, handed down to us, age by age, since the beginnings of the healing art. Experimenting physicians are Hippocratists and empiricists at one and the same time, in that they believe in the power of nature and the effi-

cacy of drugs; only they want to know what they are doing; it is not enough for them to observe and to act empirically, they want to experiment scientifically and to understand the physiological mechanism producing disease and the medicinal mechanism effecting a cure. If this were their exclusive mental tendency, it is true that experimenting physicians would be as much, as empirical physicians are little, perplexed. Indeed in the present state of medicine, we know so little about the action of drugs that, if experimenting physicians were logical, they would be reduced to doing nothing and to remaining most of the time in the state of expectancy enjoined by their doubts and uncertainties. In this sense it is possible to say that scientific physicians are always the most perplexed at a patient's bedside. That is thoroughly true; they are really perplexed, because, on the one hand, they are convinced that we can take action with the help of powerful medicinal means, while, on the other hand, their ignorance of the mechanism of such action holds them back, for the experimental scientific spirit is utterly averse to producing effects and studying phenomena without trying to understand them.

There is evidently an excess of these two radical turns of mind among empiricists and among experimenters: in practice the two points of view should be fused, and the seeming contradiction between them should disappear. What I am saying here is by no means a kind of compromise or arrangement for convenience in medical practice. I am maintaining a purely scientific opinion, because I can easily prove that the true experimental method consists in a logical union of empiricism and experimentation. In fact, we have seen that, before foreseeing facts according to the laws which govern them, we must first observe them empirically or by chance; just as before experimenting along the lines of a scientific theory, we must first experiment empirically, in order to see. Now, in this respect, empiricism is nothing but the first step of the experimental method; for, as we said, empiricism cannot be a final stage; the vague, unconscious experience, which may be called medical tact, is later transformed into a scientific idea, by the experimental method which is conscious and logical. Experimental physicians, there^ fore, are empirical to begin with; but instead of stopping at that, they try to pass through empiricism so as to reach the second step in the experimental method, i.e., exact and conscious experiment

which gives experimental knowledge of the law of phenomena. In a word, we must suffer empiricism; but trying to set it up as a system is an antiscientific tendency. As for systematic and doctrinal physicians, they are empiricists who, instead of having recourse to experimentation, take pure hypotheses, or else the facts taught them by empiricism, and join them together with the help of an ideal system, from which they later deduce their line of medical conduct.

Consequently, I think that experimenting physicians who wish to use, at the patient's bedside, only medicines whose physiological effect they understand would exaggerate in a direction that made them distort the true meaning of the experimental method. Before understanding facts, experimenters must first note them and free them from every source of error with which their minds be tainted. Experimenters must therefore first apply their minds to collecting medical or therapeutic observations empirically made. But they do still more; they are not limited to subjecting to the experimental criterion all the empirical facts that medicine presents to them ; they go out to meet them. Instead of waiting for chance or accidents to teach them the effects of medicines, they try them empirically on animals, to get indications to guide them in the experiments that they afterward make on man.

I consider then that true experimenting physicians should be no more perplexed at a patient's bedside than empirical physicians. They will make use of all the therapeutic means advised by empiricism ; only instead of using them according to authority and with a confidence akin to superstition, they will administer them with that philosophic doubt which is appropriate to true experimenters; they will verify the results on animals, and by comparative observations on man, so as to determine rigorously the relative influence of nature and of medicine in curing disease. In case it is proved that the remedy does not cure, and all the more so if it is shown to be harmful, experimenters should renounce it, and, like the Hippocratists, should await events. Certain practising physicians, fanatically convinced of the excellence of their medications, cannot understand the experimental therapeutic criticism of which I have just spoken. They say we can give sick people only medicines in which we have faith, and they think administering to our neighbors a remedy, which we doubt, is a failure of medical morals. I do

not accept this reasoning, for it would lead us both to deceive ourselves and to deceive others without scruple. As for myself, I think it better to try to enlighten ourselves, so as to deceive no one. Experimenting physicians should, therefore, not be mere physiologists waiting with folded arms for experimental medicine to be established scientifically, before taking action in behalf of their patients. Far from it, they should use the remedies that are empirically known, not only on equal terms with empiricists, but should go even further and try new medicines according to the rules suggested above. Experimental physicians, then, like empiricists, should be able to aid the sick by every means in the possession of practical medicine. What is more, with the help of the scientific spirit that guides them, they will do their part in founding experimental medicine; and that should be the most ardent wish of all physicians who want to see medicine rise out of its present state. We must suffer empiricism, as we said, as a transient and imperfect stage of medicine, but must not set it up as a system. In our faculties of medicine, we must therefore not limit ourselves, as men have actually said, to making empirical healers; that would degrade medicine and reduce it to the level of business. First of all, we must inspire young men with the scientific spirit and initiate them into the ideas and tendencies of modem science. Doing anything else would be inconsistent, besides, with the great variety of knowledge demanded of doctors, solely to enable them to cultivate medical science ; for much narrower knowledge is demanded of health ofiicers who are concerned only with empirical practice.

But the objection may be raised that experimental medicine, about which I am talking at such length, is a theoretic conception whose reality has not yet been vindicated in practice ; because facts have not demonstrated that we may expect the same scientific precision in medicine as in the experimental sciences. As far as possible, I wish to leave no doubt in the reader's mind and no ambiguity in my own thought ; I am therefore going to return to this subject with a few words, in order to show that experimental medicine is only the natural blossom of practical medical investigation, guided by a scientific spirit.

I said above that compassion and blind empiricism are the prime movers of medicine ; later came reflection bringing doubt, then scientific verification. This medical evolution can still be verified around us every day, for every man goes on learning, as does all humankind. Expectancy, whatever help it may give the tendencies of nature, can be only an incomplete method of treatment. Moreover, we must often act against the tendencies of nature. If, for example, an artery is open, we clearly must not favor nature which makes the blood come out and leads to death. We must act in the opposite direction, stop the hemorrhage and save a life. Just so, when a patient has an attack of septicemia, we must act against nature and stop the fever if we mean to cure our patient. Empiricists, then, may save patients whom expectancy would leave to die, just as expectancy might permit the recovery of a patient whom empiricism would kill. So that empiricism is also an insufficient method of treatment, in that it is uncertain and often dangerous. Now experimental medicine is only a union of expectancy with empiricism, enlightened by reasoning and experimentation. But experimental medicine will be the last to establish itself, and only then can medicine become scientific. We shall see, in fact, that all parts of medical knowledge are interrelated and are necessarily subordinate one to another in their evolution.

When a physician is called to a patient, he should decide on the diagnosis, then the prognosis, and then the treatment of the disease. The diagnosis can be established only through observation ; in recognizing a disease, physicians connect it with some form of disease already observed, known and described. Observation also gives the progress and prognosis of the disease ; physicians must know the evolution of the disease, its duration and gravity in order to predict its course and outcome. Here statistics intervene to guide physicians, by teaching them the proportion of mortal cases; and if observation has also shown that the successful and unsuccessful cases can be recognized by certain signs, then the prognosis is more certain. Finally comes the treatment: when physicians are Hippocratists, they limit themselves to expectancy; when they are empiricists they give remedies, still basing their action on observation which has taught by experiments or otherwise that such and such a remedy has succeeded in this disease a certain number of times; when physicians are systematic, they may accompany their treatment with vitalistic or other explanations, that will make no

difference in the result. Here again, only statistics are invoked to establish the value of the treatment. Such, in fact, is the state of empirical medicine, which is conjectural medicine because it is based on statistics which collect and compare cases that are analogous or more or less similar in their outer characteristics, but undefined as to their immediate causes. Conjectural medicine must necessarily precede exact medicine, which I call experimental medicine because it is based on the experimental determination of the cause of disease. In the meantime, we must resign ourselves to practising conjectural or empirical medicine; but, I repeat, though I have often said it before, we must recognize that medicine should not stop there, and that it is destined to become experimental and scientific. We are doubtless far from the time when all medicine will be scientific; but that need not prevent our conceiving it possible and making every effort to strive toward it, by trying even to-day to introduce into medicine the method that must lead us to that goal.

Medicine will necessarily first become experimental in the diseases most easy of experimental approach. Among these, let me choose an example to show my idea of how empirical medicine can become scientific. The itch is a disease whose causation is now pretty well defined scientifically; but this has not always been the case. Formerly we knew the itch and its treatment only empirically. Then we guessed about lesions in the itch and collected statistics on the value of one salve or another for curing the disease. Now that the cause of the itch is known and experimentally determined, it has all become scientific, and empiricism has disappeared. We know the tick, and by it we explain the transmission of the itch, the skin changes and the cure, which is only the tick's death through appropriate application of toxic agents. No further hypotheses need now be made about the metastasis of the itch, no further statistics collected about its treatment. We cure it always without any exception, when we place ourselves in the known experimental conditions for reaching this goal.^

Here, then, is a disease that has reached the experimental stage; and physicians are masters of it just as much as physicists and chemists are masters of a phenomenon of mineral nature. Experimenting physicians will exert their influence successively on diseases one by one, as soon as they experimentally learn their correct determinism, i.e., their immediate cause. Even the best informed empirical physicians lack the experimenter's sureness. One of the clearest cases of empirical treatment is curing fever with quinine ; yet this cure is far from being as certain as curing the itch. Diseases that have their seat in the outer organic environment, such as epidemic diseases, are the easiest to study and to analyze experimentally. These diseases will more quickly reach the stage where their causation is known and their treatment scientific. But later, in proportion as physiology progresses, we shall be able to get at the inner environment, i.e., the blood, discover there the parasitic and other changes that cause diseases and determine the medicinal, physico-chemical or specific agents capable of acting in this inner environment, altering the pathological mechanisms located there and reechoing thence throughout the whole organism.

My conception of experimental medicine is summed up above. As I have often repeated, it is nothing but the consequence of the wholly natural evolution of scientific medicine. In this respect, medicine does not differ from other sciences which have all passed through empiricism before reaching their final experimental stage. In chemistry and in physics, practical methods of extracting metals, making magnifying glasses, etc., were known before the scientific theory evolved.

Empiricism, then, also guided these sciences through their nebulous days; but only since the advent of experimental theories have physics and chemistry taken such brilliant flights as applied sciences, for we must be careful to avoid confusing empiricism with applied science. Applied science always implies pure science as its support. Medicine will doubtless pass through empiricism much more slowly and laboriously than the physico-chemical sciences; not only because the organic phenomena with which it is concerned are much more complex, but also because the requirements of medical practice, which I need not study here, help to keep medicine in the personal realm, and thus oppose the experimental development. I need not here return to what I have elsewhere so amply explained, to wit, that the spontaneity of living beings does not prevent the application of the experimental method, and that knowledge of the

simple or complex causation of vital phenomena is the one foundation of scientific medicine. The object of experimenting physicians is to discover and grasp the original causation of a series of obscure and complex morbid phenomena; as a result they will dominate all secondary phenomena; thus we have seen that, on mastering the tick which causes the itch, we naturally master all the derived phenomena. By learning the ultimate cause of poisoning with curare, we easily explain all secondary phenomena; and to find a cure, we must always go back, in the end, to the original causation of phenomena.

Medicine is destined, then, to get away from empiricism little by little; like all other sciences, it will get away by the scientific method. This deep conviction sustains and guides my scientific life. I am deaf to the physicians who ask us to explain measles and scarlet fever experimentally, and who believe they can find in them an argument against using the experimental method. These discouraging, negative objections generally come from systematic or lazy minds that prefer resting on their systems or sleeping in the dark, to working and making an effort to get away. The different branches of physico-chemical science were elucidated only gradually, step by step, by the experimental method, and they still have today obscure parts which we are studying with the help of the same method. In spite of all the obstacles that it meets, medicine will follow the same course; it will follow it necessarily. In extolling the introduction of the experimental method into medicine, I am therefore only trying to guide men's minds toward a goal that science is instinctively and unconsciously pursuing, — a goal that it will more quickly and certainly reach if it can succeed in seeing it clearly. Time will then do the rest. Of course, we shall not see scientific medicine blossoming in our day, but that is man's lot; those who sow and laboriously cultivate the field of science are not also destined to reap the harvest.

To sum up, experimental medicine, as we conceive it, includes the problem of medicine as a whole and comprises both the theory and the practice of medicine. But when I said that every physician should be an experimenter, I did not mean to suggest that each one should cultivate the whole extent of experimental medicine. Of necessity, there will always be physicians especially devoting themselves to physiological experiments, others to investigation of normal

and pathological anatomy, others to surgical or medical practice, etc. This splitting up is not bad for the progress of science ; on the contrary, practical specialties are an excellent thing for science, properly speaking, but on the condition that men devoting themselves to the investigation of a special part of medicine be so educated as to be conversant with experimental medicine as a whole, and to know the place which the special science they cultivate should occupy in that whole. By specializing in this way, they will direct their studies so as to contribute to the progress of scientific or experimental medicine. Practical studies and theoretic studies will thus work toward the same object; that is all that we can ask in a science, like medicine, which is forced to be ceaselessly in action before it is fully established.

Experimental or scientific medicine is tending on every side to establish itself on the basis of physiology. The tendency of studies published every day, whether in France or abroad, furnishes unmistakable proof. In my research and teaching at the College de France, I unfold every idea that can help or encourage this tendency in medicine. I consider this my duty as a man of science and professor of medicine at the College de France. In fact, the College de France is by no means a medical faculty in which every part of medicine should be treated systematically. By the very nature of its establishment, the College de France should always be in the forefront of science, embodying its movement and its tendencies. Consequently the course in medicine with which I am entrusted must embody the part of medical science which is by way of the greatest present development, and which involves the rest in its evolution. I have already explained myself at length on the proper character of the course in medicine at the College de France; I shall not return to that.^ Let me simply say that, while I acknowledge that the experimental trend of science must be slow to establish itself because of difiiculties inherent in the complexity of medicine, we must recognize that it is now a definite trend. In fact, this has not been brought about by the ephemeral influence of some personal system or other ; it results from the scientific evolution of medicine itself. My convictions, in this respect, are what I am seeking to impress on the

• Claude Bernard, Legons de physiologie exp4rimentale appliqu^e d la midecine ifaitea au ColUge de France). First lesson, Paris, 1857. Cotira de nUdeoine au ColUge de France. First lesson, Paris, 1855. minds of the young physicians attending my courses at the College de France. I try to show them that they are all called to contribute their share to the increase and development of experimental or scientific medicine. For that reason I ask them to familiarize themselves with the modem methods of investigation put in use in anatomical, physiological, pathological and therapeutic science; because these various branches of medicine must always remain inseparably united in theory and in practice. I tell those whose path leads them toward theory or toward pure science, never to lose sight of the medical problem, which is to preserve health and cure disease. I tell those whose career, on the contrary, guides them toward practice, never to forget that if theory is meant to enlighten practice, practice in turn should be of use to science. Physicians thoroughly imbued with these ideas will always keep their interest in the progress of science, at the same time that they do their duty as practitioners. In noting accurately and acutely the interesting cases that present themselves, they will understand how fully science may profit by them. Experimental scientific medicine will thus become the achievement of us all; and every one of us, even if he be only a simple country doctor, will make his own useful contribution.

Keturning now to the title of this long section, I conclude that empirical medicine and experimental medicine are far from being incompatible, but on the contrary must be intimately united; for both are indispensable in building up experimental medicine. I think that this conclusion is well established by all that has gone before. IV. Experimental Medicine Does Not Cokbespond to Ant Medical Doctrine or Any Philosophic System We said that experimental medicine is not a new system of medicine, but on the contrary is the negation of all systems. In fact, the advent of experimental medicine will cause all individual views to disappear from the science, to be replaced by impersonal and general theories which, as in other sciences, will be only a regular and logical coordination of facts furnished by experience.

Scientific medicine is certainly not yet well established to-day; but thanks to the experimental method which is permeating it more and more, it is tending to become an exact science. Medicine is in transition; the day of personal doctrines and systems is past, and little by little they will be replaced by theories embodying the present state of the science and showing from that point of view the results of all our efforts. But that must not make us believe that theories are ever absolute truths ; they may always be improved, and so are always mobile. That is why I have been careful to say that we must not, as men often do, confuse advancing and perfectible progressive theories, which may be improved, with scientific methods and principles that are fixed and unshakable. We must remember that the one unchangeable scientific principle, in medicine as well as in the other experimental sciences, is the absolute determinism of phenomena. We gave the name of determinism to the immediate or determining cause of phenomena. We never act on the essence of natural phenomena, but only on their determining causes; and because we act thus, determinism differs from fatalism, on which we cannot act. Fatalism assumes that the manifestation of any phenomenon is necessary and independent of its conditions, while determinism is the condition necessary to a phenomenon, whose manifestation is free. When search for the causes determining phenomena is once posited as the fundamental principle of the experimental method, materialism, spiritualism, inert matter and living matter cease to exist; only phenomena are left, whose conditions we must determine, i.e., the conditions which play the part of immediate cause. Scientific determinism ceases here; there are only words beyond, which are of course necessary, but which may delude us if we are not constantly on guard against the traps which our minds perpetually set for themselves.

As experimental medicine, like all the experimental sciences, should not go beyond phenomena, it does not need to be tied to any system; it is neither vitalistic, nor animistic, nor organistic, nor solidistic, nor humoral ; it is simply the science which tries to reach the immediate causes of vital phenomena in the healthy and in themorbid state. It has no reason, in fact, to encumber itself with systems, none of which can ever embody the truth.

In this connection it may be useful to recall, in a few words, the essential characteristics of the scientific method and to show how the ideas derived from it differ from systematic and doctrinal ideas. In the experimental method we never make experiments except to see or to prove, i.e., to control or verify. As a scientific method, the experimental method rests wholly on the experimental verification of a scientific hypothesis. We obtain this verification with the help, sometimes of a fresh observation (observational science), sometimes of an experiment (experimental science). In| the experimental method, the hypothesis is a scientific idea that we submit to experiment. Scientific invention consists in the creation of fortunate and fertile hypotheses; these are suggested by the feeling or even the genius of the men of science who create them.