An Introduction to the Study of Experimental Medicine

Now, what we call the immediate cause of a phenomenon is nothing but the physical and material condition in which it exists or appears. The object of the experimental method or the limit of every scientific research is therefore the same for living bodies as for inorganic bodies; it consists in finding the relations which connect any phenomenon with its immediate cause, or putting it differently, it consists in defining the conditions necessary to the appearance of the phenomenon. Indeed, when an experimenter succeeds in learning the necessary conditions of a phenomenon, he is, in some sense, its master ; he can predict its course and its appearance, he can promote or prevent it at will. An experimenter's object, then, is reached; through science, he has extended his power over a natural phenomenon.

We shall therefore define physiology thus : the science whose object it is to study the phenomena of living beings and to determine the material conditions in which they appear. Only by the analytic or experimental method can we attain the determination of the conditions of phenomena, in living bodies as well as in inorganic bodies; for we reason in identically the same way in experimenting in all the sciences. For physiological experimenters, neither spiritualism nor materialism can exist. These words belong to a philosophy which has grown old ; they will fall into disuse through the progress of science. We shall never know either spirit or matter; and if this were the proper place I should easily show that on one side, as on the other, we quickly fall into scientific negations. The conclusion is that all such considerations are idle and useless. It is our sole concern to study phenomena, to learn their material conditions and manifestations, and to determine the laws of those manifestations.

First causes are outside the realm of science ; they forever escape us in the sciences of living as well as in those of inorganic bodies. The experimental method necessarily turns aside from the chimerical search for a vital principle; vital force exists no more than mineral force exists, or, if you like, one exists quite as much as the other. The word, force, is merely an abstraction which we use for linguistic convenience. For mechanics, force is the relation of a movement to its cause. For physicists, chemists and physiologists, it is fundamentally the same. As the essence of things must always remain unknown, we can learn only relations, and phenomena are merely the results of relations. The properties of living bodies are revealed only through reciprocal organic relations. A salivary gland, for instance, exists only because it is in relation with the digestive system, and because its histological units are in certain relations one with another and with the blood. Destroy these relations by isolating the

units of the organism, one from another in thought, and the salivarygland simply ceases to be. A scientific law gives us the numerical relation of an effect to its cause, and that is the goal at which science stops. When we have the law of a phenomenon, we not only know absolutely the conditions determining its existence, but we also have the relations applying to all its variations, so that we can predict modifications of the phenomenon in any given circumstances.

As a corollary to the above we must add that neither physiologists nor physicians need imagine it their task to seek the cause of life or the essence of disease. That would be entirely wasting one's time in pursuing a phantom. The words, life, death, health, disease, have no objective reality. We must imitate the physicists in this matter and say, as Newton said of gravitation : '^Bodies fall with an accelerated motion whose law we know : that is a fact, that is reality. But the first cause which makes these bodies fall is utterly unknown. To picture the phenomenon to our minds, we may say that the bodies fall as if there were a force of attraction toward the centre of the earth, quasi esset attractio. But the force of attraction does not exist, we do not see it ; it is merely a word used to abbreviate speech.'' When a physiologist calls in vital force or life, he does not see it ; he merely pronounces a word ; only the vital phenomenon exists, with its material conditions; that is the one thing that he can study and know.

To sum up, the object of science is everywhere the same : to learn the material conditions of phenomena. But though this goal is the same in the physico-chemical and in biological sciences, it is much harder to reach in the latter because of the mobility and complexity of the phenomena which we meet. V. The Necessary Conditions of Natural Phenomena Are Absolutely Determined in Living Bodies as Well AS IN Inorganic Bodies We must acknowledge as an experimental axiom that in living beings as well as in inorganic bodies the necessary conditions of every phenomenon are absolutely determined. That is to say, in other terms, that when once the conditions of a phenomenon are known and fulfilled, the phenomenon must always and necessarily be reproduced

at the will of the experimenter. Negation of this proposition would be nothing less than negation of science itself. Indeed, as science is simply the determinate and the determinable, we must perforce accept as an axiom that, in identical conditions, all phenomena are identical and that, as soon as conditions are no longer the same, the phenomena cease to be identical. This principle is absolute in the phenomena of inorganic bodies as well as in those of living beings, and the influence of life, whatever view of it we take, can nowise alter it. As we have said, what we call vital force is a first cause analogous to all other first causes, in this sense, that it is utterly unknown. It matters little whether or not we admit that this force differs essentially from the forces presiding over manifestations of the phenomena of inorganic bodies, the vital phenomena which it governs must still be determinable ; for the force would otherwise be blind and lawless, and that is impossible. The conclusion is that the phenomena of life have their special law because there is rigorous determinism in the various circumstances constituting conditions necessary to their existence or to their manifestations ; and that is the same thing. Now in the phenomena of living bodies as in those of inorganic bodies, it is only through experimentation, as I have already often repeated, that we can attain knowledge of the conditions which govern these phenomena and so enable us to master them.

Everything so far said may seem elementary to men cultivating the physico-chemical sciences. But among naturalists and especially among physicians, we find men who, in the name of what they call vitalism, express most erroneous ideas on the subject which concerns us. They believe that study of the phenomena of living matter can have no relation to study of the phenomena of inorganic matter. They look on life as a mysterious supernatural influence which acts arbitrarily by freeing itself wholly from determinism, and they brand as materialists all who attempt to reconcile vital phenomena with definite organic and physico-chemical conditions. These false ideas are not easy to uproot when once established in the mind ; only the progress of science can dispel them. But vitalistic ideas, taken in the sense which we have just indicated, are just a kind of medical superstition, — a belief in the supernatural. Now, in medicine, belief in occult causes, whether it is called vitalism or is otherwise named, encourages ignorance and gives birth to a sort of unintentional quackery ; that is to say, the belief in an inborn, indefinable science. Con-

fidence in absolute determinism in the phenomena of life leads, on the contrary, to real science, and gives the modesty which comes from the consciousness of our little learning and the difficulty of science. This feeling incites us, in turn, to work toward knowledge; and to this feeling alone, science in the end owes all its progress. I should agree with the vitalists if they would simply recognize that living beings exhibit phenomena peculiar to themselves and unknown in inorganic nature. I admit, indeed, that manifestations of life cannot be wholly elucidated by the physico-chemical phenomena known in inorganic nature. I shall later explain my view of the part played in biology by physico-chemical sciences; I will here simply say that if vital phenomena differ from those of inorganic bodies in complexity and appearance, this difference obtains only by virtue of determined or determinable conditions proper to themselves. So if the sciences of life must differ from all others in explanation and in special laws, they are not set apart by scientific method. Biology must borrow the experimental method of physico-chemical sciences, but keep its special phenomena and its own laws.

In living bodies, as in inorganic bodies, laws are immutable, and the phenomena governed by these laws are bound to the conditions on which they exist, by a necessary and absolute determinism. I use the word determinism here as more appropriate than the word fatalism, which sometimes serves to express the same idea. Determinism in the conditions of vital phenomena should be one of the axioms of experimenting physicians. If they are thoroughly imbued with the truth of this principle, they will exclude all supernatural intervention from their explanations ; they will have unshaken faith in the idea that fixed laws govern biological science; and at the same time they will have a reliable criterion for judging the often variable and contradictory appearance of vital phenomena. Indeed, starting with the principle that immutable laws exist, experimenters will be convinced that phenomena can never be mutually contradictory, if they are observed in the same conditions ; and if they show variations, they will know that this is necessarily so because of the intervention or interference of other conditions which alter or mask phenomena. There will be occasion thenceforth to try to learn the conditions of these variations, for there can be no effect without a cause. Determinism thus becomes the foundation of all scientific progress and criticism. If we find disconcerting or even contradictory results in performing

an experiment, we must never acknowledge exceptions or contradictions as real. That would be unscientific. We must simply and necessarily decide that conditions in the phenomena are different, whether or not we can explain them at the time. I assert that the word exception is unscientific; and as soon as laws are known, no exception indeed can exist, and this expression, like so many others, merely enables us to speak of things whose causation we do not know. Every day we hear physicians use the words : ordinarily, more often, generally, or else express themselves numerically by saying, for instance : nine times out of ten, things happen in this way. I have heard old practitioners say that the words ^'always" and "never" should be crossed out of medicine. I condemn neither these restrictions nor the use of these locutions if they are used as empirical approximations about the appearances of phenomena when we are still more or less ignorant of the exact conditions in which they exist. But certain physicians seem to reason as if exceptions were necessary ; they seem to believe that a vital force exists which can arbitrarily prevent things from always happening alike ; so that exceptions would result directly from the action of mysterious vital force. Now this cannot be the case ; what we now call an exception is a phenomenon, one or more of whose conditions are unknown ; if the conditions of the phenomena of which we speak were known and determined, there would be no further exceptions, medicine would be as free from them as is any other science. For instance, we might formerly say that sometimes the itch was cured and sometimes not; but now that we attack the cause of this disease, we cure it always. Formerly it might be said that a lesion of the nerves brought on paralysis, now of feeling, and again of motion; but now we know that cutting the anterior spinal nerve paralyzes motion only. Motor paralysis occurs consistently and always, because its condition has been accurately determined by experimenters.

The certainty with which phenomena are determined should also be, as we have said, the foundation of experimental criticism, whether applied to one's self or to others. A phenomenon, indeed, always appears in the same way if conditions are similar; the phenomenon never fails if the conditions are present, just as it does fail to appear if the conditions are absent. Thus an experimenter who has made an experiment, in conditions which he believes were determined, may happen not to get the same results in a new series of investigations

as in his first observation; in repeating the experiment, with fresh precautions, it may happen again that, instead of his first result, he may encounter a wholly different one. In such a situation, what is to be done ? Should we acknowledge that the facts are indeterminable ? Certainly not, since that cannot be. We must simply acknowledge that experimental conditions, which we believed to be known, are not known. We must more closely study, search out and define the experimental conditions, for the facts cannot be contradictory one to another; they can only be indeterminate. Facts never exclude one another, they are simply explained by differences in the conditions in which they are born. So an experimenter can never deny a fact that he has seen and observed, merely because he cannot rediscover it. In the third part of this introduction, we shall cite instances in which the principles of experimental criticism which we have just suggested, are put in practice.

VI. To Have Determinism for Phenomena^ in Biological as in Physico-Chemical Sciences, We Must Reduce the Phenomena to Experimental Conditions as Definite and Simple as Possible As a natural phenomenon is only the expression of ratios and relations and connections, at least two bodies are necessary to its appearance. So we must always consider, first, a body which reacts or which manifests the phenomenon; second, another body which acts and plays the part of environment in relation to the first. It is impossible to imagine a body wholly isolated in nature; it would no longer be real, because there would be no relation to manifest its existence.

In phenomenal relations, as nature presents them to us, more or less complexity always prevails. In this respect mineral phenomena are much less complex than vital phenomena ; this is why the sciences dealing with inorganic bodies have succeeded in establishing themselves more quickly. In living bodies, the complexity of phenomena is immense, and what is more, the mobility accompanying vital characteristics makes them much harder to grasp and to define.

The properties of living matter can be learned only through their relation to the properties of inorganic matter; it follows that the biological sciences must have as their necessary foundation the physico-chemical sciences from which they borrow their means of analysis and their methods of investigation. Such are the necessary reasons for the secondary and backward evolution of the sciences concerned with the phenomena of life. But though the complexity of vital phenomena creates great obstacles, we must not be appalled, for, as we have already said, unless we deny the possibility of biological science, the principles of science are everywhere the same. So we may be sure that we are on the right road and that in time we shall reach the scientific result that we are seeking, that is to say, determinism in the phenomena of living beings.

We can reach knowledge of definite elementary conditions of phenomena only by one road, viz., by experimental analysis. Analysis dissociates all the complex phenomena successively into more and more simple phenomena, until they are reduced, if possible, to just two elementary conditions. Experimental science, in fact, considers in a phenomenon only the definite conditions necessary to produce it. Physicists try to picture these conditions to themselves, more or less ideally in mechanics or mathematical physics. Chemists successively analyze complex matters; and in thus reaching either elements or definite substances (individual compounds or chemical species), they attain the elementary or irreducible conditions of phenomena. In the same way, biologists should analyze complex organisms and reduce the phenomena of life to conditions that cannot be analyzed in the present state of science.

Experimental physiology and medicine have no other goal. When faced by complex questions, physiologists and physicians, as well as physicists and chemists, should divide the total problem into simpler and simpler and more and more clearly defined partial pr6b- lems. They will thus reduce phenomena to their simplest possible material conditions and make application of the experimental method easier and more certain. All the analytic sciences divide problems, in order to experiment better. By following this path, physicists and chemists have succeeded in reducing what seemed the most complex phenomena to simple properties connected with well-defined mineral species. By following the same analytic path, physiologists should succeed in reducing all the vital manifestations of a complex organism to the play of certain organs, and the action of these organs to the properties of well-defined tissues or organic units. Anatomicophysiological experimental analysis, which dates from Galen, has just

this meaning, and histology, in pursuing the same problem to-day, is naturally coming closer and closer to the goal. Though we can succeed in separating living tissues into chemical elements or bodies, still these elementary chemical bodies are not elements for physiologists. In this respect biologists are more like physicists than chemists, for they seek to determine the properties of bodies and are much less preoccupied with their elementary composition. In the present state of the science, it would be impossible to establish any relation between the vital properties of bodies and their chemical composition ; because tissues and organs endowed with the most diverse properties are at times indistinguishable from the point of view of their elementary chemical composition. Chemistry is most useful to physiologists in giving them means of separating and studying individual compounds, true organic products which play important parts in the phenomena of life.

Organic individual compounds, though well defined in their properties, are still not active elements in physiological phenomena ; like mineral matter, they are, as it were, only passive elements in the organism. For physiologists, the truly active elements are what we call anatomical or histological units. Like the organic individual compounds, these are not chemically simple; but physiologically considered, they are as simplified as possible in that their vital properties are the simplest that we know, — vital properties which vanish when we happen to destroy this elementary organized part. However, all ideas of ours about these elements are limited by the present state of our knowledge ; for there can be no question that these histological units, in the condition of cells and fibres, are still complex. That is why certain naturalists refuse to give them the names of elements and propose to call them elementary organisms. This appellation is in fact more appropriate ; w^e can perfectly well picture to ourselves a complex organism made up of a quantity of distinct elementary organisms, uniting, joining and grouping together in various ways, to give birth first to the different tissues of the body, then to its various organs; anatomical mechanisms are themselves only assemblages of organs which present endlessly varied combinations in living beings. When we come to analyze the comple:?: manifestations of any organism, we should therefore separate the complex phenomena and reduce them to a certain number of simple properties belonging to elementary organisms; then syn-

thetically reconstruct the total organism in thought, by reuniting and ordering the elementary organisms, considered at first separately, then in their reciprocal relations. When physicians, chemists or physiologists, by successive experimental analyses, succeed in determining the irreducible element of a phenomenon in the present state of their science, the scientific problem is simplified, but its nature is not changed thereby ; and men of science are no nearer to absolute knowledge of the essence of things. ^Nevertheless, they have gained what it is truly important to obtain, to wit, knowledge of the necessary conditions of the phenomenon and determination of the definite relation existing between a body manifesting its properties and the immediate cause of this manifestation. The object of analysis, in biological as in physico-chemical science, is, after all, to determine and, as far as possible, to isolate the conditions governing the occurrence of each phenomenon. We can act on the phenomena of nature only by reproducing the natural conditions in which they exist ; and we act the more easily on these conditions in proportion as they have first been better analyzed and reduced to a greater state of simplicity. Real science exists, then, only from the moment when a phenomenon is accurately defined as to its nature and rigorously determined in relation to its material conditions, that is, when its law is known. Before that, we have only groping and empiricism.

VII. In Living Bodies, Just as in Inorganic Bodies, the Existence of Phenomena Is Always Doubly Conditioned The most superficial examination of what goes on around us shows that all natural phenomena result from the reaction of bodies one against another. There always come under consideration the hody, in which the phenomenon takes place, and the outward circumstance or the environment which determines or invites the body to exhibit its properties. The conjunction of these conditions is essential to the appearance of the phenomenon. If we suppress the environment, the phenomenon disappears, just as if the body had been taken away. The phenomena of life, as well as those of inorganic bodies, are thus doubly conditioned. On the one hand, we have the organism in which vital phenomena come to pass; on the other hand, the cosmic environment in which living bodies, like inor-

ganic bodies, find the conditions essential to the appearance of their phenomena. The conditions necessary to life are found neither in the organism nor in the outer environment, but in both at once. Indeed, if we suppress or disturb the organism, life ceases, even though the environment remains intact; if, on the other hand, we take away or vitiate the environment, life just as completely disappears, even though the organism has not been destroyed.

Thus phenomena appear as results of contact or relation of a body with its environment. Indeed, if we absolutely isolate a body in our thought, w^e annihilate it in so doing; and if, on the contrary, we multiply its relations with the outer world, we multiply its properties. Phenomena, then, are definite relations of bodies; we always conceive these relations as resulting from forces outside of matter, because we cannot absolutely localize them in a single body. For physicists, universal attraction is only an abstract idea; manifestation of this force requires the presence of two bodies; if only one body is present, we can no longer conceive of attraction. For example, electricity results from the action of copper and zinc in certain chemical conditions; but if we suppress the interrelation of bodies, electricity, — an abstraction without existence in itself, — ceases to appear. In the same way, life results from contact of the organism with its environment; we can no more understand it through the organism alone than through the environment alone. It is therefore a similar abstraction, that is to say, a force which appears as if it were outside of matter.

But however the mind conceives the forces of nature, that cannot alter an experimenter's conduct in any respect. For him the problem reduces itself solely to determining the material conditions in which a phenomenon appears. These conditions once known, he can then master the phenomenon ; by supplying or not supplying them, he can make the phenomenon appear or disappear at will. Thus physicists and chemists exert their power over inorganic bodies ; thus physiologists gain empire over vital phenomena. Living bodies, however, seem at first sight to elude the experimenter's action. We see the higher organisms uniformly exhibit their vital phenomena, in spite of variations in the surrounding cosmic environment, and from another angle we see life extinguished in an organism after a certain length of time without being able to find reasons in the

external environment for this extinction. But, as we have already said, there is an illusion here, resulting from incomplete and superficial analysis of the conditions of vital phenomena. Ancient science was able to conceive only the outer environment ; but to establish the science of experimental biology, we must also conceive an inner environment. I believe I was the first to express this idea clearly and to insist on it, the better to explain the application of experimentation to living beings. Since the outer environment, on the other hand, infiltrates into the inner environment, knowing the latter teaches us the former's every influence. Only by passing into the inner, can the influence of the outer environment reach us, whence it follows that knowing the outer environment cannot teach us the actions born in, and proper to, the inner environment. The general cosmic environment is common to living and to inorganic bodies; but the inner environment created by an organism is special to each living being. Now, here is the true physiological environment ; this it is which physiologists and physicians should study and know, for by its means they can act on the histological units which are the only effective agents in vital phenomena. Nevertheless, though so deeply seated, these units are in communication with the outer world ; they still live in the conditions of the outer environment perfected and regulated by the play of the organism. The organism is merely a living machine so constructed that, on the one hand, the outer environment is in free communication with the inner organic environment, and, on the other hand, the organic units have protective functions, to place in reserve the materials of life and uninterruptedly to maintain the humidity, warmth and other conditions essential to vital activity.

Sickness and death are merely a dislocation or disturbance of the mechanism which regulates the contact of vital stimulants with organic units. In a word, vital phenomena are the result of contact between the organic units of the body with the inner physiological environment; this is the pivot of all experimental medicine. Physiologists and physicians gain mastery over the phenomena of life by learning which conditions, in this inner environment, are normal and which abnormal, for the appearance of vital activity in the organic units ; for apart from complexity of conditions, phenomena exhibiting life, like physico-chemical phenomena, result from contact between an active body and the environment in which it acts.

VIII. In Biological as in Physico-Chemical Science, Determinism Is Possible, Because Matter in Living as in In- organic Bodies Can Possess No Spontaneity To sum up, the study of life includes two things: (1) Study of the properties of organized units; (2) study of the organic environment, i.e., study of the conditions which this environment must fulfill to permit the appearance of vital activities. Physiology, pathology and therapeutics rest on this double knowledge; apart from this, neither medical science nor any truly scientific or effectual therapeutics exists.

In living organisms it is convenient to distinguish between three kinds of definite bodies: first, chemical elements; second, organic and inorganic individual compounds; third, organized anatomical units. Of about 70 elements known to chemistry to-day, only 16 are found in that most complex of organisms, the organism of man. But these 16 elements combine with one another to form the various liquid, solid and gaseous substances of the organism. Oxygen and nitrogen, however, are merely dissolved in the organic fluids ; and in living beings, seem to act as elements. The inorganic individual compounds (earthy salts, phosphates, chlorides, sulphates, etc.) are essential constituents in the composition of living bodies, but are taken ready-made directly from the outer world. Organic individual compounds are also constituents of living bodies, but by no means borrowed from the outer world; they are made by the vegetable or animal organism; among such substances are starch, sugar, fat, albumen, etc., etc. When extracted from the body, they preserve their properties because they are not alive ; they are organic products, but not organized. Anatomical units stand alone as organized living parts. These parts are irritable and, under the influence of various stimulants, exhibit properties exclusively characteristic of living beings. They live and nourish themselves, and their nourishment creates and preserves their properties, which means that they cannot be cut off from the organism without more or less rapidly losing their vitality.

Though very different from one another in respect to their functions in the organism, these three classes of bodies all show physicochemical reactions under the influence of the outer stimuli, — ^warmth, light, electricity; but living parts also have the power of being irritable, i.e., reacting under the influence of certain stimuli in a way specially characteristic of living tissues, such as muscular contraction, nervous transmission, glandular secretion, etc. But whatever the variety presented by the three classes of phenomena, whether the reaction be physico-chemical or vital, it is never in any way spontaneous. The phenomenon always results from the influence exerted on the reacting body by a physico-chemical stimulant outside itself.