An Introduction to the Study of Experimental Medicine

Finally, in concluding this section, we may say that in all experimental reasoning there are two possibilities: either the experimenter's hypothesis will be disproved or it will be proved by experiment. When experiment disproves his preconceived idea, the experimenter must discard or modify it. But even when experiment fully proves his preconceived idea, the experimenter must still doubt; for since he is dealing with an unconscious truth, his reason still demands a counterproof.

We have just said that one must doubt, but by no means be sceptical. A sceptic, indeed, who believes nothing, no longer has a foundation on which to establish his criterion, and consequently he finds it impossible to build up a science ; the sterility of his unhappy mind results at once from the error of his perception and from the imperfection of his reason. After having posited the principle that investigators must doubt, we added that doubt will apply only to the soundness of their opinions, or of their ideas as experimenters, or to the value of their means of investigation, as observers, but never to determinism, the very principle of experimental science. Let us return in a few words to this fundamental point.

Experimenters must doubt their intuition, i.e., the a priori idea or the theory which serves as their starting point; this is why it is an absolute principle always to submit one's idea to the experimental criterion so as to test its value. But just what is the foundation of this experimental criterion? This question may seem superfluous, after having repeatedly said that facts judge the idea and give us experience. Facts alone are real, it is said; and we must leave the matter to them, wholly and exclusively. Again, it is a fact, a sheer fact, men often repeat; there is no use in discussing, we must accept it. Of course I admit that facts are the only realities that can give form to the experimental idea and at the same time serve as its control ; but this is on condition that reason accepts them. I think that blind belief in fact, which dares to silence reason, is as dangerous to the experimental sciences as the beliefs of feeling or of faith which also force silence on reason. In a word, in the experimental method as in everything else, the only real criterion is reason.

A fact is nothing in itself, it has value only through the idea connected with it or through the proof it supplies. We have said elsewhere that, when one calls a new fact a discovery, the fact itself is not the discovery, but rather the new idea derived from it ; in the same way, when a fact proves anything, the fact does not itself give the proof, but only the rational relation which it establishes between the phenomenon and its cause. This relation is the scientific truth which we now must discuss further.

Let us recall how we characterized mathematical truths and experimental truths. Mathematical truths, once acquired, we said, are conscious and absolute truths, because the ideal conditions in which they exist are also conscious and known by us in an absolute way. Experimental truths, on the contrary, are unconscious and relative, because the real conditions on which they exist are un^ conscious and can be known by us only in their relation to the present state of our science. But if the experimental truths, which serve as foundation for our reasoning, are so wrapped up in the complex reality of natural phenomena that they appear to us only in shreds, these experimental truths rest, none the less, on principles that are absolute because, like those of mathematical truths, they speak to our consciousness and our reason. Indeed the absolute principle of experimental science is conscious and necessary determinism in the conditions of phenomena. So that, given no matter what natural phenomenon, experimenters can never acknowledge variation in the

embodiment of this phenomenon, unless new conditions have at the same time occurred in its coming to pass; what is more, they have an a 'priori certainty, that these variations are determined by rigorous, mathematical relations. Experiment only shows us the form of phenomena ; but the relation of a phenomenon to a definite cause is necessary and independent of experiment ; it is necessarily mathematical and absolute. Thus we see that the principle of the criterion in experimental sciences is fundamentally identical with that of the mathematical sciences, since in each case the principle is expressed by a necessary and absolute relation between things. Only in the experimental sciences these relations are surrounded by numerous, complex and infinitely varied phenomena which hide them from our sight. With the help of experiment, we analyze, we dissociate these phenomena, in order to reduce them to more and more simple relations and conditions. In this way we try to lay hold on scientific truth, i.e., find the law that shall give us the key to all variations of the phenomena. Thus experimental analysis is our only means of going in search of truth in the natural sciences, and the absolute determinism of phenomena, of which we are conscious a 'priori, is the only criterion or principle which directs and supports us. In spite of our eiforts, we are still very far from this absolute truth; and it is probable, especially in the biological sciences, that it will never be given us to see it in its nakedness. But this need not discourage us, for we are constantly nearing it ; and moreover, with the help of our experiments, we grasp relations between phenomena which, though partial and relative, allow us more and more tO' extend our power over nature.

It follows from the above that, if a phenomenon, in an experiment, had such a contradictory appearance that it did not necessarily connect itself with determinate causes, then reason should reject the fact as non-scientific. We should wait or by direct experiments seek the source of error which may have slipped into the observation. Indeed, there must be error or insufiiciency in the observation; for to accept a fact without a cause, that is, indeterminate in its necessary conditions, is neither more nor less than the negation of science. So that, in the presence of such a fact, men of science must never hesitate; they must believe in science and doubt their means of investigation. They will, therefore, perfect their means of observation and will make every effort to get out of the darkness ; but they

will never deny the absolute determinism of the phenomena; because it is precisely the recognition of determinism that characterizes true men of science. In medicine, we are often confronted with poorly observed and indefinite facts which form actual obstacles to science, in that men always bring them up, saying : it is a fact, it must be accepted. Kational science based, as we have said, on a necessary determinism, must never repudiate an accurate and well-observed fact ; but on the same principle, it ought not to encumber itself with apparent facts collected without precision, and possessing no kind of meaning, which are used as a double-edged weapon to support or disprove the most diverse opinions. In short, science rejects the indeterminate; and in medicine, when we begin to base our opinions on medical tact, on inspiration, or on more or less vague intuition about things, we are outside of science and offer an example of that fanciful medicine which may involve the greatest dangers, by surrendering the health and life of the sick to the whims of an inspired ignoramus. True science teaches us to doubt and, in ignorance, to refrain.

We said above that experimenters, who see their ideas confirmed by an experiment, should still doubt and require a counterproof. Indeed, proof that a given condition always precedes or accompanies a phenomenon does not warrant concluding with certainty that a given condition is the immediate cause of that phenomenon. It must still be established that, when this condition is removed, the phenomenon will no longer appear. If we limited ourselves to the proof of presence alone, we might fall into error at any moment and believe in relations of cause and effect where there was nothing but simple coincidence. As we shall later see, coincidences form one of the most dangerous stumbling blocks encountered by experimental scientists in complex sciences like biology. It is the post hoc, ergo propter hoc of the doctors, into which we may very easily let ourselves be led, especially if the result of an experiment or an observation supports a preconceived idea.

Counterproof, then, is a necessary and essential characteristic of the conclusion of experimental reasoning. It is the expression of philosophic doubt carried as far as possible. Counterproof decides whether the relation of cause to effect, which we seek in phenomena, has been found. To do this, it removes the accepted cause, to see if the effect persists, relying on that old and absolutely true adage: suhlata causa, tollitur ejfectus. This is what we still call the experimentum crucis.

We must not confuse a counterexperiment or counterproof with what has been called comparative experiment. As we shall later see, this is only a comparative observation resorted to, in complex circumstances, to simplify phenomena and to forearm oneself against unforeseen sources of error; counterproof, on the contrary, is a counterjudgment dealing directly with the experimental conclusion and forming one of its necessary terms. Indeed, proof, in science, never establishes certainty without counterproof. Analysis can be absolutely proved only when the synthesis, which demonstrates it, provides the counterproof or counterexperiment. Similarly a synthesis made at the outset should be demonstrated later by analysis. Feeling for this necessary, experimental counterproof constitutes the scientific feeling par excellence. It is familiar to physicists and chemists; but it is far from being as well understood by physicians. In most cases, when we see two phenomena in physiology or medicine going together and following one another in a constant order, we think we may conclude that the first is the cause of the second. This would be a false judgment in very many cases ; statistical tables of presence or of absence never establish experimental demonstrations. In complex sciences like medicine, we must at the same time make use of comparative experiment and of counterproof. Some physicians fear and avoid counterproof; as soon as they make observations in the direction of their ideas, they refuse to look for contradictory facts, for fear of seeing their hypothesis vanish. We have already said that this is a very poor spirit; if we mean to find truth, we can solidly settle our ideas only by trying to destroy our own conclusions by counterexperiments.

Now the only proof that one phenomenon plays the part of cause in relation to another is by removing the first, to stop the second. I shall not further emphasize this principle of the experimental method at this point, because I shall later take the opportunity to return to it, giving special examples which will explain my thought. Let me summarize by saying that experimenters should always push their investigation to the point of counterproof; without that, their

experimental reasoning would not be complete. Counterproof establishes the necessary determinism of phenomena; and thus alone can satisfy reason to which, as we have said, we must always bring back any true scientific criterion. Experimental reasoning, whose different terms we have examined in the preceding section, sets itself the same goal in all the sciences. Experimenters try to reach determinism ; with the help of reasoning and of experiment they try to connect natural phenomena with their necessary conditions or, in other words, with their immediate causes. By this means, they reach the law which enables them to master phenomena. All natural philosophy is summarized in knowing the law of phenomena. The whole experimental problem may be reduced to foreseeing and directing phenomena. But this double goal can be attained, in living bodies, only by certain special principles of experimentation which we must point out in the following chapters.

The spontaneity enjoyed by beings endowed with life has been one of the principal objections urged against the use of experimentation in biological studies. Every living being indeed appears to us provided with a kind of inner force, which presides over manifestations of life more and more independent of general cosmic influence in proportion as the being rises higher in the scale of organization. In the higher animals and in man, for instance, this vital force seems to result in withdrawing the living being from general physico-chemical influences and thus making the experimental approach very difiicult.

Inorganic bodies offer no parallel; whatever their nature, they are all devoid of spontaneity. As the manifestation of their properties is therefore absolutely bound up in the physico-chemical conditions surrounding them and forming their environment, it follows that the experimenter can reach them and alter them at will. On the other hand, all the phenomena of a living body are in such reciprocal harmony one with another that it seems impossible to separate any part without at once disturbing the whole organism. Especially in higher animals, their more acute sensitiveness brings with it still more notable reactions and disturbances.

Many physicians and speculative physiologists, with certain anatomists and naturalists, employ these various arguments to attack experimentation on living beings. They assume a vital force in opposition to physico-chemical forces, dominating all the phenomena of life, subjecting them to entirely separate laws, and making the organism an organized whole which the experimenter may not touch without destroying the quality of life itself. They even go so far as to say that inorganic bodies and living bodies differ radically from this point of view, so that experimentation is applicable to the former and not to the latter. Cuvier, who shares this opinion and thinks that physiology should be a science of observation and of deductive anatomy, expresses himself thus: "All parts of a living body are interrelated ; they can act only in so far as they act all together ; trying to separate one from the whole means transferring it to the realm of dead substances; it means entirely changing its essence."

If the above objections were well founded, we should either have to recognize that determinism is impossible in the phenomena of life, and this would be simply denying biological science ; or else we should have to acknowledge that vital force must be studied by special methods, and that the science of life must rest on different principles from the science of inorganic bodies. These ideas, which were current in other times, are now gradually disappearing; but it is essential to extirpate their very last spawn, because the so-called vitalistic ideas still remaining in certain minds are really an obstacle to the progress of experimental science.

I propose, therefore, to prove that the science of vital phenomena must have the same foundations as the science of the phenomena of inorganic bodies, and that there is no difference in this respect between the principles of biological science and those of physico-chemical science. Indeed, as we have already said, the goal which the experimental method sets itself is everywhere the same ; it. consists in connecting natural phenomena with their necessary conditions or with their immediate causes. In biology, since these conditions are known, physiologists can guide the manifestation of vital phenomena as physicists guide the natural phenomena, the laws of which they have discovered ; but in doing so, experimenters do not act on life.

Yet there is absolute determinism in all the sciences, because every phenomenon being necessarily linked with physico-chemical conditions, men of science can alter them to master the phenomenon, i.e., to prevent or to promote its appearing. As to this, there is absolutely no question in the case of inorganic bodies. I mean to prove that it is the same with living bodies, and that for them also determinism exists. II. Manifestation of Pkopeeties of Living Bodies Is Connected WITH THE Existence of Certain Physico-Chemical Phenomena Which Regulate Their Appearance

The manifestation of properties of inorganic bodies is connected with surrounding conditions of temperature and moisture by means of which the experimenter can directly govern mineral phenomena. Living bodies at first sight do not seem capable of being thus influenced by neighboring physico-chemical conditions; but that is merely a delusion depending on the animal having and maintaining within himself the conditions of warmth and moisture necessary to the appearance of vital phenomena. The result is that an inert body, obedient to cosmic conditions, is linked with all their variations, while a living body on the contrary remains independent and free in its manifestations ; it seems animated by an inner force that rules all its acts and liberates it from the influence of surrounding physicochemical variations and disturbances. This quite different aspect of the manifestations of living bodies as compared with the behavior of inorganic bodies has led the psysiologists, called vitalists, to attribute to the former a vital force ceaselessly at war with physicochemical forces and neutralizing their destructive action on the living organism. According to this view, the manifestations of life are determined by spontaneous action of this special vital force, instead of being, like the manifestations of inorganic bodies, the necessary results of conditions or of the physico-chemical influences of a surrounding environment. But if we consider it, we shall soon see that the spontaneity of living bodies is simply an appearance and the result of a certain mechanism in completely determined environments; so that it will be easy, after all, to prove that the behavior of living bodies, as well as the behavior of inorganic bodies, is dominated by a necessary determinism linking them with conditions of a purely physico-chemical order.

Let us note, first of all, that this kind of independence of living beings in the cosmic environment appears only in complex higher animals. Inferior beings, such as the infusoria, reduced to an elementary organism, have no real independence. These creatures exhibit the vital properties with which they are endowed, only under the influence of external moisture, light or warmth, and as soon as one or more of these conditions happens to fail, the vital manifes-

tation ceases, because the parallel physico-chemical phenomenon has stopped. In vegetables the manifestation of vital phenomena is linked in the same way with conditions of warmth, moisture and light in the surrounding environment. It is the same again with cold-blooded animals; the phenomena of life are benumbed or stimulated according to the same conditions. Now the influences producing or retarding vital manifestations in living beings are exactly the same as those which produce, accelerate or retard manifestations of physr ico-chemical phenomena in inorganic bodies, so that instead of following the example of the vitalists in seeing a kind of opposition or incompatibility between the conditions of vital manifestations and the conditions of physico-chemical manifestations, we must note, on the contrary, in these two orders of phenomena a complete parallelism and a direct and necessary relation. Only in warm-blooded animals do the conditions of the organism and those of the surrounding environment seem to be independent; in these animals indeed the manifestation of vital phenomena no longer suffers the alternations and variations that the cosmic conditions display; and an inner force seems to join combat with these influences and in spite of them to maintain the vital forces in equilibrium. But fundamentally it is nothing of the sort; and the semblance depends simply on the fact that, by the more complete protective mechanism which we shall have occasion to study, the warm-blooded animaFs internal environment comes less easily into equilibrium with the external cosmic environment. External influences, therefore, bring about changes and disturbances in the intensity of organic functions only in so far as the protective system of the organism's internal environment becomes insufficient in given conditions.

III. Physiological Phenomena in the Higher Animals Take Place in Perfected Internal Organic Environments En- dowed WITH Constant Physico-Chemical Properties Thoroughly to understand the application of experimentation to living beings, it is of the first importance to reach a definite judgment on the ideas which we are now explaining. When we examine a higher, i.e., a complex living organism, and see it fulfill its different functions in the general cosmic environment common to all the phe-

nomena of nature, it seems to a certain extent independent of this environment. But this appearance results simply from our deluding ourselves about the simplicity of vital phenomena. The external phenomena vrhich v^e perceive in the living being are fundamentally very complex; they are the resultant of a host of intimate properties of organic units whose manifestations are linked together with the physico-chemical conditions of the internal environment in which they are immersed. In our explanations we suppress this inner environment and see only the outer environment before our eyes. But the real explanation of vital phenomena rests on study and knowledge of the extremely tenuous and delicate particles which form the organic units of the body. This idea, long ago set forth in biology by great physiologists, seems more and more true in proportion as the science of the organization of living beings makes progress. We must, moreover, learn that the intimate particles of an organism exhibit their vital activity only through a necessary physicochemical relation with immediate environments which we must also study and know. Otherwise, if we limit ourselves to the survey of total phenomena visible from without, we may falsely believe that a force in living beings violates the physico-chemical laws of the general cosmic environment, just as an untaught man might believe that some special force in a machine, rising in the air or running along the ground, violated the laws of gravitation. 'NoWy a living organism is nothing but a wonderful machine endowed with the most marvellous properties and set going by means of the most complex and delicate mechanism. There are no forces opposed and struggling one with another ; in nature there can be only order and disorder, harmony or discord.

In experimentation on inorganic bodies, we need take account of only one environment, the external cosmic environment ; while in the higher living animals, at least two environments must be considered, the external or extra-organic environment and the internal or intraorganic environment. In my course on physiology at the Faculty of Sciences, I explain each year these ideas on organic environment, — new ideas which I regard as fundamental in general physiology ; they are also necessarily fundamental in general pathology, and the same thoughts will guide us in adapting experimentation to living beings, For, as I have said elsewhere, the great difficulties that we meet in experimentally determining vital phenomena and in applying suit-

able means to altering them are caused by the complexity involved in the existence of an internal organic environment.'^ Physicists and chemists experimenting on inert bodies need consider only the external environment; by means of the thermometer, barometer and other instruments used in recording and measuring the properties of the external environment, they can always set themselves in equivalent conditions. For physiologists these instruments no longer suffice; and yet the internal environment is just the place where they should use them. Indeed, the internal environment of living beings is always in direct relation with the normal or pathological vital manifestations of organic units. In proportion as we ascend the scale of living beings, the organism grows more complex, the organic units become more delicate and require a more perfected internal environment. The circulating liquids, the blood serum and the intra-organic fluids all constitute the internal environment.

In living beings the internal environment, which is a true product of the organism, preserves the necessary relations of exchange and equilibrium with the external cosmic environment ; but in proportion as the organism grows more perfect, the organic environment becomes specialized and more and more isolated, as it were, from the surrounding environment. In vegetables and in cold-blooded animals, as we have said, this isolation is less complete than in warm-blooded animals ; in the latter the blood serum maintains an almost fixed and constant temperature and composition. But these differing conditions do not constitute differences of nature in different living beings ; they are merely improvements in the isolating and protecting mechanisms of their environment. Vital manifestations in animals vary only because the physico-chemical conditions of their internal environments vary ; thus a mammal, whose blood has been chilled either by natural hibernation or by certain lesions of the nervous system, closely resembles a really cold-blooded animal in the properties of its tissues.

To sum up, from what has been said we can gain an idea of the enormous complexity of vital phenomena and of the almost insuperable difficulties which their accurate determination opposes to physiologists forced to carry on experimentation in the internal or organic * Claude Bernard, Legons sur la physiologie et la pathologie du systime nerveux. Legon d'oiwerture, Dec. 17, 1856. Paris, 1858, Vol. I. — Cours de pathologie experimentale. {The Medical Times, 1860.)

environments. These obstacles, however, cannot terrify us if we are thoroughly convinced that we are on the right road. Absolute determinism exists indeed in every vital phenomenon ; hence biological science exists also; and consequently the studies to which we are devoting ourselves will not all be useless. General physiology is the basic biological science toward which all others converge. Its problem is to determine the elementary condition of vital phenomena. Pathology and therapeutics also rest on this common foundation. By normal activity of its organic units, life exhibits a state of health ; by abnormal manifestation of the same units, diseases are characterized ; and finally through the organic environment modified by means of certain toxic or medicinal substances, therapeutics enables us to act on the organic units. To succeed in solving these various problems, we must, as it were, analyze the organism, as we take apart a machine to review and study all its works ; that is to say, before succeeding in experimenting on smaller units we must first experiment on the machinery and on the organs. We must, therefore, have recourse to analytic study of the successive phenomena of life, and must make use of the same experimental method which physicists and chemists employ in analyzing the phenomena of inorganic bodies. The difficulties which result from the complexity of the phenomena of living bodies arise solely in applying experimentation ; for fundamentally the object and principles of the method are always exactly the same.

IV. The Aim of Experimentation Is the Same in Study of Phenomena of Living Bodies as in Study of Phenomena If the physicist and the physiologist differ in this, that one busies himself with phenomena taking place in inorganic matter, and the other with phenomena occurring in living matter, still they do not differ in the object which they mean to attain. Indeed, they both set themselves a common object, viz., getting back to the immediate cause of the phenomena which they are studying.