An Introduction to the Study of Experimental Medicine

As in physiology, the only scientific criticism possible in pathology and in therapeutics is experimental criticism; and whether applied to ourselves or to the work of others, this criticism should always be based on absolute determination of facts. Experimental criticism, as we have seen, should reject statistics as a foundation for experimental therapeutic and pathological science. In pathology and therapeutics, we should repudiate undetermined facts, that is to

say, those badly made, and sometimes imaginary, observations which are constantly brought forward as perpetual objections. As in physiology, there are crude facts which can enter into scientific reasoning only on condition that they be determined and exactly defined as to their necessary conditions. But it is characteristic of criticism in pathology and therapeutics, first and foremost to require comparative observation and experiment. How, indeed, can a physician judge the etiology, if he does not make a comparative experiment to eliminate all the secondary circumstances, that might beeome sources of error, and make him take mere coincidences for relations of cause and effect? Especially in therapeutics, the need of comparative experiment has always struck physicians endowed with the scientific spirit. We cannot judge the influence of a remedy on the course and outcome of a disease if we do not previously know the natural course and outcome of the disease. That is why Pinel said in his clinic : "This year we will observe diseases without treating them, and next year we will treat them." Scientifically, we ought to adopt Pinel' s idea without, however, accepting the long-range, comparative experiment which he proposed. Diseases, in fact, may vary in seriousness from one year to another; Sydenham's observations on the undetermined or unknown influence of what he calls the epidemic genius prove it. To be valid, comparative experiments have therefore to be made at the same time and on as comparable patients as possible. In spite of that, such comparisons still bristle with immense difficulties which physicians must strive to lessen ; for comparative experiment is the sine qua non of scientific experimental medicine; without it a physician walks at random and becomes the plaything of endless illusions. A physician, who tries a remedy and cures his patients, is inclined to believe that the cure is due to his treatment. Physicians often pride themselves on curing all their patients with a remedy that they use.

But the first thing to ask them is whether they have tried doing nothing, i.e., not treating other patients; for how can they otherwise know whether the remedy or nature cured them? Gall VTrote a little known book * on the question as to what is nature's share and what is the share of medicine in healing disease, and he very naturally concludes that their respective shares are quite hard to * Gall, Philosophische medicinische Untersuchungen uher Kunst und Natur im gesunden und kranken Zustand des Menschen. Leipzig, 1800.

assign. We may be subject daily to the greatest illusions about the value of treatment, if we do not have recourse to comparative experiment. I shall recall only one recent example concerning the treatment of pneumonia. Comparative experiment showed, in fact, that treatment of pneumonia by bleeding, which was believed most efficacious, is a mere therapeutic illusion. From all this, I conclude that comparative observation and experiment are the only solid foundation for experimental medicine, and that physiology, pathology and therapeutics must be subject to this criticism in common.

According to everything so far said in this Introduction, the principal obstacles encountered by experimental medicine lie in the enormous complexity of the phenomena studied. I need not return to this point already explained from every angle. But besides these wholly material and, so to speak, objective difficulties, there are obstacles to experimental medicine arising from vicious methods, bad mental habits and certain false ideas about which we shall now say a few words.

I certainly do not claim to have been the first to propose applying physiology to medicine. That was long ago recommended, and numerous attempts have been made in this direction. In my works and my teaching at the College de France, I am therefore merely following out an idea which is already bearing fruit through its application to medicine. More than ever to-day, young physicians are advancing along this path, rightly considered the path of progress. However, I have frequently seen the application of physiology to medicine misunderstood, so that it not only fails to produce the good results which we have a right to expect, but becomes actually harmful, and thus furnishes arguments to the detractors of experimental medicine. It is therefore most important to make the subject plain ; for in dealing with the important question of method, we shall find a fresh opportunity to define more exactly the true point of view of what we call experimental medicine.

Experimental medicine differs in object from the medicine of observation, just as the sciences of observation in general differ from the experimental sciences. The object of any science of observation is to discover the laws of natural phenomena so as to foresee them; but it cannot master them or alter them at pleasure. Astronomy is typical of these sciences; we can foresee astronomical phenomena, but we cannot change them in any way. The object of an experimental science is to discover the laws of natural phenomena, for the purpose not only of foreseeing them, but of regulating them at pleasure and mastering them : such are physics and chemistry.

Among physicians, there are some who actually believe that medicine should remain a science of observation, i.e., that it should be able to foresee the course and outcome of diseases, but should not directly act on disease. There are others, and I am one of them, who think that medicine can be an experimental science, i.e., that it should delve into the interior of organisms and find ways of altering and, to a certain extent, regulating the hidden springs of living machines. Observing physicians look on a living organism as a little world contained in the great world, like a kind of ephemeral living planet whose motions are ruled by laws which we discover by simple observation, so as to foresee the progress and evolution of vital phenomena in health or disease, but without ever being able to alter their natural course in any way. This doctrine is found in Hippocrates in its purest form. Medicine of simple observation obviously excludes all manner of active medical intervention; for this reason it is also known as expectant medicine, that is to say, medicine that observes and foresees the course of diseases without aiming to act directly on their progress.^ It is rarely that we find a physician purely Hippocratic in this respect, and it would be easy to prove that many physicians, who loudly applaud Hippocratism, do not trust to its precepts in the least when they give themselves up to the most active and disordered flights of empirical medication. Not that I condemn these therapeutic attempts which, most of the time, are only experimentations to see; only I say that this is not Hippocratic medicine, but empiricism. Empirical physicians, acting more or less blindly, are, after all, experimenting on vital phenomena, and thus class themselves in the empirical period of experimental medicine.

Experimental medicine is therefore medicine that claims knowledge of the laws of healthy and diseased organisms, not only so as to foresee phenomena, but also so as to be able to regulate and alter them ^ LeQon d'ouverture du cours de mSdecine au ColUge de France (Revue des cours scientifiquea, Dec. 31, 1864). within certain limits. Accordingly, we easily perceive that medicine necessarily tends to become experimental, and that every physician who gives his patients active medicines cooperates in building up experimental medicine. But if such action, on the part of experimenting physicians, is to transcend empiricism and deserve the name of science, it must be based on knowledge of the laws governing action in the organism's inner environment, whether in a healthy or a pathological state. The scientific basis of experimental medicine is physiology; we have often said this; it must be proclaimed aloud, because without it no medical science is possible. Diseases at bottom are only physiological phenomena in new conditions still to be determined; toxic and medicinal action, as we shall see, come back to simple physiological changes in properties of the histological units of our tissues. In a word, physiology must be constantly applied to medicine, if we are to understand and explain the mechanism of disease and the action of toxic and medicinal agents. Now, precisely this application of physiology must here be carefully defined.

We saw above how experimental medicine differs from Hippocratism and from empiricism; but we did not say that experimental medicine should therefore renounce observational medicine or the empirical use of medicines; far from it, experimental medicine makes use of medical observation as a necessary support. In fact, experimental medicine never systematically rejects any fact or popular observation ; it must examine everything experimentally, and it seeks the scientific explanation of facts which observational medicine and empiricism have already noted. Experimental medicine, then, is what I might call the second period of scientific medicine, the first period being observational medicine; and quite naturally, therefore, the second period is added to the first and rests on it. The first requirement, then, in practising experimental medicine, is to be an observing physician and to start from pure and simple observations of patients made as completely as possible; experimental science comes next, analyzing every symptom by trying to connect it with explanations and vital laws that shall include the relation of the pathological state to the normal or physiological condition.

But in the present state of biological science, no one can presume to explain pathology by physiology alone ; we must move in that direction because it is the scientific path, but we must shun belief in the illusion that our problem is solved. For the moment, therefore, the prudent and reasonable thing to do is to explain all that we can explain in a disease by physiology and leave what is still inexplicable to the future progress of biological science. This kind of analysis, advancing only step by step as the progress of physiological science permits, isolates the essential elements of a disease by elimination, a little at a time, grasps its characteristics more accurately and allows us to guide therapeutics more intelligently. Besides, the analytic, progressive advance still keeps the individual character and aspect of the disease. But if we take advantage, instead, of a few possible connections between pathology and physiology, to try to explain the whole disease at a single stroke, then we lose sight of the patient, we distort the disease, and by our false application of physiology, we retard experimental medicine, instead of promoting its progress.

Unfortunately I must blame not only pure physiologists for the wrong application of physiology to pathology, but also professional pathologists and physicians. In various recent publications on medicine, whose physiological tendencies, by the way, I approve and praise, I see that before any exposition of medical observations, the authors begin with a summary of everything learned by experimental physiology about phenomena connected with the disease with which they are concerned. Then they contribute observations of patients, sometimes without definite scientific object, sometimes to show that physiology and pathology are in agreement. But aside from the fact that agreement is not always easy to prove, because points in experimental physiology are often still under consideration, I find this sort of procedure essentially disastrous to medical science, in that it subordinates the more complex science, pathology, to physiology, a simpler science. This is, in fact, the inverse of what we previously said should be done : we should first of all state the medical problem as given by observation of the disease, then try to find the physiological explanation, by experimentally analyzing the pathological phenomena. But in this analysis, medical observation must never disappear or be lost sight of ; it must remain as the constant basis or common ground of all our studies and explanations.

In this work, I cannot develop as a whole the things that I have just said, because I have had to limit myself to giving the results of my experience in physiological science with which I am most familiar. In publishing a simple essay on the principles of scientific medicine, my idea is to be of some use to medicine. Medicine, indeed, is so vast that we can never hope to find a man able to cultivate all parts of it fruitfully at one time. But in the part where each physician takes up his quarters, he must thoroughly understand the scientific connections between all the medical sciences, 90 as to avoid scientific anarchy by guiding his investigations in a direction useful to the whole. I am not practising clinical medicine here ; but I must take account of it, nevertheless, and assign it the first place in experimental medicine. So if I were planning a treatise on experimental medicine, I should go to work by invariably making observation of disease the basis of every experimental analysis. I should then proceed with my explanations, symptom by symptom, until I had exhausted all the information obtainable from present experimental physiology, and the result of all this would be medical observation reduced to its simplest terms.

In saying above that we must explain by experimental physiology only what can be explained in disease, I do not want my idea misunderstood or taken as an admission that there are things in disease which can never be physiologically explained. My idea is just the reverse, because I believe that we shall explain everything in pathology, but little by little and in step with the development of experimental physiology. We can just now explain nothing about certain diseases, for instance the eruptiva diseases, because the related physiological phenomena are unknown. So the objection, which some physicians find here, to physiology as a help to medicine, is not worthy of consideration. That kind of argumentation is tinged with scholasticism and proves that those who use it have no correct idea of such a science as experimental medicine can be.

To sum up, as the natural foundation of experimental medicine, experimental physiology cannot suppress observation of the sick or lessen its importance. Moreover, physiological knowledge is not only indispensable in explaining disease, but is also necessary to good clinical observation. For example, I have seen observers surprised into describing as accidents certain thermal phenomena which occasionally result from nerve lesions ; if they had been physiologists, they would have known how to evaluate morbid symptoms which are really nothing but physiological phenomena.

II. Scientific Ignorance and Certain Illusions of the Scientific Spirit Hinder the Development of Experimental We have just said that knowledge of physiology is indispensable to physicians ; we must therefore cultivate the physiological sciences, if we wish to further the development of experimental medicine. This is all the more necessary, because it is the only way to provide a foundation for scientific medicine, and unfortunately we are still far from the time when we shall see the scientific spirit generally prevailing among physicians. IN^ow the absence of the scientific habit of mind is a serious hindrance, because it favors belief in occult forces, rejects determinism in vital phenomena, and leads to the notion that the phenomena of living beings are governed by mysterious, vital forces which are continually invoked. When an obscure or inexplicable phenomenon presents itself, instead of saying "I do not know," as every scientific man should do, physicians are in the habit of saying, "This is life" ; apparently without the least idea that they are explaining darkness by still greater darkness. We must therefore get used to the idea that science implies merely determining the conditions of phenomena ; and we must always seek to exclude life entirely from our explanations of physiological phenomena as a whole. Life is nothing but a word which means ignorance, and when we characterize a phenomenon as vital, it amounts to saying that we do not know its immediate cause or its conditions. Science should always explain obscurity and complexity by clearer and simpler ideas. Now since nothing is more obscure, life can never explain anything. I emphasize this point, because I have seen even chemists at times appeal to life to explain certain physico-chemical phenomena peculiar to living beings. Thus the ferment in yeaSt is an organic, living material which has the property of converting sugar into alcohol, carbonic acid and several other products.

I have sometimes heard it said that the property of decomposing sugar was due to the life inherent in a globule of yeast. This vitalistic explanation means nothing and explains nothing about the action of yeast. We do not know the nature of this property, but it must necessarily belong to the physico-chemical order and be as precisely defined as, for instance, the property of platinum sponge which produces a more or less analogous action that cannot be attributed to vital force. In

a word, all the properties of living matter are, at bottom, either known and defined properties, in which case we call them physicochemical properties, or else unknown and undefined properties, in which case we name them vital properties. Certainly a special force in living beings, not met with elsewhere, presides over their organization ; but the existence of this force cannot in any way change our idea of the properties of organic matter, — matter which, when once created, is endowed with fixed and determinate, physico-chemical properties. Vital force is, therefore, an organizing and nutritive force ; but it does not in any way determine the manifestation of the properties of living matter. In a word, physiologists and physicians must seek to reduce vital properties to physico-chemical properties, and not physico-chemical properties to vital properties

The habit of vitalistic explanation makes us credulous and promotes the introduction of erroneous or absurd data into science. Thus, quite recently I was consulted by an honorable and much respected practising physician who asked my opinion of a most unusual case, of which, he said, he was very sure, because he had taken all precautions necessary to observing it well: here was a woman in good health except for a few nervous anomalies, who had neither eaten nor drunk anything for several years. Evidently the physician was persuaded that vital force is capable of anything, so that he sought no other explanation. The slightest idea of science, however, and the simplest notions of physiology, would have been enough to undeceive him, by showing that his statement very nearly amounted to saying that a candle can go on shining and burning for several years without growing any shorter.

Belief that the phenomena of living beings are dominated by an indeterminate vital force often also gives experimentation a false basis and puts a vague word in place of exact experimental analysis. I have seen physicians submit questions to experimental analysis in which they took as their starting point the vitality of certain organs, the idiosyncrasy of certain individuals or the antagonism of certain medicines. Now, vitally, idiosyncrasy and antagonism are merely vague words which should first be qualified and reduced to a definite meaning. In the experimental method, then, it is a matter of absolute principle always to take, as our starting point for experimentation or reasoning, an exact fact or a good observation, and not a vague word. When the discussions of physicians and

naturalists lead to nothing, it is usually because they fail to conform to this analytic precept. In a word, in experimentation on living beings, as with inorganic bodies, it is essential, before beginning our experimental analysis of a phenomenon, to make sure that the phenomenon exists and never to let ourselves be deceived by words that lose sight of facts as they are. As we have elsewhere explained, doubt is the foundation of experimentation; yet we must not confuse philosophic doubt with that systematic negation which casts doubt on the very principles of science. We must doubt only theories, and we must doubt even them only to the point of experimental determinism. Some physicians believe that the scientific spirit sets no limit to doubt. Aside from these physicians, who deny medical science by admitting that nothing positive can be known, others deny it by the opposite method, admitting, as they do, that they have learned their medicine they know not how, and are masters of it through a kind of intuitive science which they call clinical sense or instinct. In medicine, as in other practical sciences, I do not of course question the existence of what is called tact or clear-sightedness. Everyone knows, in fact, that habit may give a kind of empirical knowledge of things sufficient to guide practitioners, even though they cannot always precisely account for it at first. But what I blame is willfully staying in this empirical state and not trying to get out of it. By attentive observation and study, we can always manage to account for our actions and so succeed in transmitting our knowledge to others. Besides, I do not deny that the practice of medicine has severe requirements ; but here I am talking pure science and am attacking medical tact as an anti-scientific datum whose natural exaggerations are decidedly harmful to science.

Another false opinion, which is pretty well accredited and even professed by great practising physicians, is expressed in saying that medicine is not destined to become a science, but only an art, and that physicians accordingly should be artists, not men of science. I find this idea erroneous and essentially harmful to the development of experimental medicine. First, what is an artist ? An artist is a man who carries out a personal idea or feeling in a work of art. Here, then, are two things: the artist and his work; the artist is necessarily judged by his work. But what can a medical artist be ? If he is a physician who treats disease according to his personal idea or feeling, then where is the work of art by which the medical

artist is to be judged ? Is it cure of the disease ? That would be a strange kind of work of art, and the physician's authorship would be seriously disputed by nature. When a great painter or a great sculptor makes a beautiful picture or a magnificent statue, no one imagines that the statue grew out of the earth or that the picture made itself, while we can perfectly well maintain that a disease has cured itself and can often prove that the cure would have been better without the artist's interference. Then what has become of the criterion, or medical work of art ? The criterion evidently disappears; because no physician's ability can be judged by the number of patients that he says he has cured ; he must first of all prove scientifically that it was he who cured them, and not nature. I shall not further emphasize this untenable medical claim to art. In reason, physicians can be men of science only, or, in the meantime, empiricists. Empiricism, which means experience at bottom (kfiTeipiay experience), is only unconscious or non-rational experience, acquired by every-day observation of facts, in which the experimental method itself originates (see p. 12). But as we shall see again in the next paragraph, empiricism in its true sense is merely the first step in experimental medicine. Empirical physicians should strive toward science, for though they often decide in practice according to unconscious experience, they should at least still guide themselves by induction based on as solid medical learning as pos^ sible.

In a word, since there is no such thing as a medical work of art, there is no such thing as a medical artist ; physicians calling themselves such injure medical science, because they exalt a physician's personality by lowering the importance of science ; thus they prevent men from seeking, in the experimental study of phenomena, the support and criterion which they believe they, through inspiration or mere feeling, have within themselves. But as I just said, this supposed therapeutic inspiration is often supported by no other proofs than some chance fact which might favor an untaught man or a charlatan, just as much as an educated man. This bears no sort of relation to the artist's inspiration which is embodied at last in a work judged by all the world, and always requiring, for its execution, exact study often accompanied by unwearied labor. In my opinion, then, the inspiration of physicians, who do not rely on experimental science, is mere fantasy; and in the name of science and humanity they should be rebuked and proscribed.

To sum up, experimental medicine, which is a synonym for scientific medicine, can be established only by spreading the scientific spirit more and more among physicians. In my opinion, the one thing to do, to reach this goal, is to give our young men solid instruction in experimental physiology. I do not mean to say that physiology is the whole of medicine; I have explained myself elsewhere on this point, but I do mean to say that experimental physiology is the most scientific part of medicine, and that in studying it, young physicians will acquire scientific habits which they will later carry into pathological and therapeutic investigation. The wish that I am expressing here roughly corresponds to Laplace's idea: when he was asked why, since medicine was not a science, he had proposed admitting physicians to the Academy of Sciences; he answered. "This is why : to get them among men of science."

III. Empirical and Experimental Medicine Are by No Means Incompatible ; on the Contrary, They Must Be Inseparable For a long time, men have said and repeated that the physicians most learned in physiology are the worst physicians, and that they are the most awkward when action is necessary at the patient's bedside. Does this mean that physiological science is harmful to practice? In that case, I must have taken a completely false point of view. We must therefore carefully study this opinion, which is a favorite theme of many practising physicians, but which. I, for my part, consider completely erroneous.

To begin with, we must remember that the practice of medicine is exceedingly complex, involving any number of social and extrascientific questions. Even in practical veterinary medicine, therapeutics is often dominated by considerations of profit or of agriculture. I recall my membership in a commission studying what was to be done to prevent the ravages of certain murrains of homed cattle. We were all weighing physiological and pathological considerations, to decide on the proper treatment to cure the sick animals, when a practising veterinarian took the floor to say that this was not the question; and he proved clearly that curative treatment would be the ruin of agriculture, and that the best thing to do was to slaughter the sick animals and turn them to the best possible account. Considerations of this kind never enter into human medicine, because

preserving human life is the physician's sole aim. Yet physicians, in their treatment, often have to take account of the so-called influence of the moral over the physical, and also of any number of family and social considerations which have nothing to do with science. Therefore, an accomplished practising physician should be not only learned in his science, but also upright and endowed with keenness, tact and good sense. Practising physicians exert an influence in every rank of society. In numberless cases, physicians are the custodians of state interests in major affairs of public administration ; at the same time they are the confidants of families and often hold reputation and most cherished interests in their hands. Able practitioners can acquire great and legitimate influence among men, because apart from science, they have a moral influence on society. And so, like Hippocrates, everyone having the dignity of medicine at heart has always insisted strongly on moral qualities in physicians.

I have no intention of discussing here the social and moral influence of physicians nor of penetrating what might be called the mysteries of medical practice; I am simply treating the scientific side and am separating it so as to judge its influence better. I certainly do not here intend to study the question whether an educated physician would treat his patients better or worse than an uneducated one. Put in that form, the question would be absurd; I naturally assume two physicians equally well educated in methods of treatment, and I intend to consider here only whether the scientific physician, i.e., the physician endowed with the experimental spirit, will treat his patient less successfully than the empirical physician who contents himself with noting facts solely on the basis of medical tradition, or the systematic physician who acts according to the principles of some doctrine or other.

In medicine, there have always been two divergent tendencies resulting from the very nature of things. The first tendency in medicine, arising from the kindly feelings of man, is to help a neighbor in trouble, and to relieve him with remedies or by moral or religious means. Medicine must therefore have been mingled with religion, from its beginning, while possessing at the same time numberless more or less active agents. Found by chance or of necessity, these remedies were later handed down by tradition, either alone or together with religious practices. But after this first flight, which started, so to speak, from the heart, men must have begun to reflect,