An Introduction to the Study of Experimental Medicine

I do not intend to go into these difficult yet fundamental problems about the relative properties of combined or combining bodies ; they will find their proper place elsewhere. I shall here only repeat that phenomena merely express the relations of bodies, whence it follows that, by dissociating the parts of a whole, we must make phenomena cease if only because we destroy the relations. It follows also, in physiology, that analysis, which teaches us the properties of isolated elementary parts, can never give us more than a most incomplete ideal synthesis ; just as knowing a solitary man would not bring us knowledge of all the institutions which result from man's association, and which can reveal themselves only through social life. In a word, when we unite physiological elements, properties appear which were imperceptible in the separate elements. We must there^ fore always proceed experimentally in vital synthesis, because quite characteristic phenomena may result from more and more complex union or association of organized elements. All this proves that these elements, though distinct and self-dependent, do not therefore play the part of simple associates; their union expresses more than addition of their separate properties. I am persuaded that the obstacles surrounding the experimental study of psychological phenomena are largely due to difficulties of this kind ; for despite their marvellous character and the delicacy of their manifestations, I find it impossible not to include cerebral phenomena, like all other phe^ nomena of living bodies, in the laws of scientific determinism.

Physiologists and physicians must therefore always consider organisms as a whole and in detail at one and the same time, without ever losing sight of the peculiar conditions of all the special phenomena whose resultant is the individual. Yet particular facts are never scientific; only generalization can establish science. But here we must avoid a double stumbling block; for if excess of detail is anti-scientific, excessive generalization creates an ideal science no longer connected with reality. This stumbling block, unimportant to a contemplative naturalist, is large for physicians who must first of all seek objective, practical truths. We must doubless admire those great horizons dimly seen by the genius of a Goethe, an Oken, a Cams, a Geoffrey Saint-Hilaire, a Darwin, in which a general conception shows us all living beings as the expression of types ceaselessly transformed in the evolution of organisms and species, — types in which every living being individually disappears like a reflection of

the whole to which it belongs. In medicine we can also rise to the most abstract generalizations, whether we take the naturalist's point of view and conceive diseases as morbid species to be classified nosologically, or whether we start from the physiological point of view and consider that disease does not exist, in the sense that it is only a special case of a general physiological state. Doubtless all these brilliant views do, after a fashion, guide and serve us. But if we gave ourselves up exclusively to hypothetical contemplation, we should soon turn our backs on reality; and in my opinion, we should misunderstand true scientific philosophy, by setting up a sort of opposition or exclusion between practice, which requires knowledge of particulars, and generalizations which tend to mingle all in all.

A physician, in fact, is by no means physician to living beings in general, not even physician to the human race, but rather, physician to a human individual, and still more physician tO' an individual in certain morbid conditions peculiar to himself and forming what is called his idiosyncrasy. Hence it seems to follow that medicine, in contrast with other sciences, should be established more and more on particulars. This opinion is incorrect and based only on appearances ; for in all sciences, generalization leads to the law of phenomena and the true scientific goal. Only we must recognize that all the morphological generalizations to which we alluded above are too superficial and are therefore insufficient for physiologists and physicians. Naturalists, physiologists and physicians have wholly different problems in view ; their investigations advance in far from parallel lines; hence we cannot, for instance, exactly superpose a physiological scale on the geological scale. Physiologists and physicians delve much more deeply than zoologists into the problem of biology; physiologists consider the general conditions necessary to vital phenomena as well as the various changes to which they may be subject. But physicians cannot content themselves with knowing that all vital phenomena occur in identical conditions among all human beings; they must go still further by studying the details of these conditions in each individual considered in given morbid conditions. Only after delving, then, as deeply as possible into the secrets of vital phenomena in the normal and pathological states can physiologists and physicians attain illuminating and fertile generalizations.

The primary essence of life is a developing organic force, the force which constituted the mediating nature of Hippocrates and the archeus faher of Van Helmont. But whatever our idea of the nature of this force, it is always exhibited concurrently and parallel with the physico-chemical conditions proper to vital phenomena. Through study, then, of physico-chemical details, physicians will learn to understand individualities as special cases included in a general law, and will discover there, as everywhere, an harmonious generalization of variety in unity. But since physicians deal with variety, they must always seek to define it in their studies and to comprehend it in their generalizations.

If I had to define life in a single phrase, I should clearly express my thought by throwing into relief the one characteristic which, in my opinion, sharply differentiates biological science. I should say : life is creation. In fact, a created organism is a machine which necessarily works by virtue of the physico-chemical properties of its constituent elements. To-day we differentiate three kinds of properties exhibited in the phenomena of living beings: physical properties, chemical properties and vital properties. But the term ^Vital properties" is itself only provisional; because we call properties vital which we have not yet been able to reduce to physico-chemical terms; but in that we shall doubtless succeed some day. So that what distinguishes a living machine is not the nature of its physicochemical properties, complex as they may be, but rather the creation of the machine which develops under our eyes in conditions proper to itself and according to a definite idea which expresses the living being^s nature and the very essence of life.

When a chicken develops in an egg, the formation of the animal body as a grouping of chemical elements is not what essentially distinguishes the vital force. This grouping takes place only according to laws which govern the chemico-physical properties of matter; but the guiding idea of the vital evolution is essentially of the domain of life and belongs neither to chemistry nor to physics nor to anything else. In every living germ is a creative idea which develops and exhibits itself through organization. As long as a living being persists, it remains under the influence of this same creative vital force, and death comes when it can no longer express itself; here as everywhere, everything is derived from the idea which alone creates and guides; physico-chemical means of expression are common to all natural phenomena and remain mingled, pell-mell, like the

letters of the alphabet in a box, till a force goes to fetch them, to express the most varied thoughts and mechanisms. This same vital idea preserves beings, by reconstructing the living parts disorganized by exercise or destroyed by accidents or diseases. To the physico-chemical conditions of this primal development, then, we must always refer our explanation of life, whether in the normal or the pathological state. We shall see, indeed, that physiologists and physicians can really act only indirectly through animal physicochemistry, that is to say, through physics and chemistry worked out in the special field of life, where the necessary conditions of all phenomena of living organisms develop, create and support each other according to a definite idea and obedient to rigorous determinisms.

As we have said, the experimental method and the principles of experimentation are identical for the phenomena of inorganic bodies and the phenomena of living bodies. But it cannot be the same with experimental practice, and it is easy to conceive that the peculiar organization of living bodies requires special processes for its analysis and must offer difficulties sui generis. However, the considerations and special precepts, which we shall present to physiologists, to forearm them against sources of error in experimental practice, have to do only with the delicacy, mobility and fugitiveness of vital qualities and the complexity of the phenomena of life. Physiologists, indeed, have only to take apart the living machine, and with the help of tools and processes borrowed from physics and chemistry, to study and measure the various vital phenomena whose law they seek to discover.

Each of the sciences possesses, if not an individual method, at least particular processes; and the sciences, moreover, serve as instruments one for another. Mathematics serves as an instrument for physics, chemistry and biology in different degrees; physics and chemistry serve as powerful instruments for physiology and medicine. In the mutual service which sciences render one another, we must of course distinguish between the men of science, who use, and those who carry forward each science. Physicists and chemists are not mathematicians because they make calculations; physiologists are not chemists or physicists because they make use of chemical reagents

or physical instruments, any more than chemists and physicists are physiologists because they study the composition or properties of certain animal or vegetable fluids or tissues. Each science has its problem and its point of view which we may not confuse without risk of leading scientific investigation astray. Yet this confusion has often occurred in biological science which, because of its complexity, needs the help of all the other sciences. We have seen, and we still often see chemists and physicists who, instead of confining themselves to the demand that living bodies furnish them suitable means and arguments to establish certain principles of their own sciences, try to absorb physiology and reduce it to simple physicochemical phenomena. They offer explanations or systems of life which tempt us at times by their false simplicity, but which harm biological science in every case, by bringing in false guidance and inaccuracy which it then takes long to dispel. In a word, biology has its own problem and its definite point of view ; it borrows from other sciences only their help and their methods, not their theories. This help from other sciences is so powerful that, without it, the development of the science of vital phenomena would be impossible. Previous knowledge of the physico-chemical sciences is therefore decidedly not, as is often said, an accessory to biology, but, on the contrary, is essential to it and fundamental. That is why I think it proper to call the physico-chemical sciences allied sciences, and not sciences accessory to physiology. We shall see that anatomy is also a science allied to physiology, just as physiology itself, which requires the help of anatomy and of all the physico-chemical sciences, is the science most closely allied to medicine and forms its true scientific foundation.

The application of physico-chemical sciences to physiology and the use of their processes as instruments, suited to the analysis of the phenomena of life, present a great many difficulties inherent, as we have said, in the mobility and fugitiveness of vital phenomena. The spontaneity and mobility enjoyed by living beings make the properties of organized bodies very hard to fix and to study. We must return for an instant here to the nature of these difficulties, as I have already had occasion to do in my lectures.-^

* Claude Bernard, Legons sur les propri4t4s physiologiques des alterations pathologiques des Uquides de Vorganisme. Paris, 1859, Vol. I. Legon d'ouvertv/re, Dec. 9, 1857. A living body differs essentially from an inorganic body from the point of view of the experimenter. An inorganic body has no sort of spontaneity; as its properties are in equilibrium with outside conditions, it soon settles into physico-chemical indifference, i.e., into stable equilibrium with its surroundings. Hence, all the phenomenal changes that it experiences will necessarily come from alterations occurring in surrounding circumstances; and we can easily see that by taking strict account of these circumstances, we can be sure of having the experimental conditions necessary to a good experiment. A living body, especially in the hi^er animals, never falls into chemico-physical indifference to the outer environment; it has ceaseless motions, an organic evolution apparently spontaneous and constant ; and though this evolution requires outer circumstances for its manifestation, it is nevertheless independent in its advance and modality. As proof of this, we see living beings born, develop, fall ill and die, without the conditions of the outer world changing for the observer.

It follows that, in experimenting on inorganic bodies with the help of such instruments as the barometer, thermometer and hygrometer, we can put ourselves in identical conditions and consequently carry on well-defined and similar experiments. Physiologists and physicians have rightly imitated the physicists and have sought to make their experiments more accurate by using the same instruments. But we can see at once that outer conditions whose changes are of such importance to physicists and chemists are of much less value to physicians. Alterations in the phenomena of inorganic bodies are, in fact, always brought about by an outer cosmic change, and it happens at times that a very slight alteration in the surrounding temperature or in barometric pressure leads to important changes in the phenomena of inorganic bodies. But in man and in the higher animals the phenomena of life may alter without any appreciable outer cosmic change, and slight thermometric or barometric changes often exert no real influence on vital manifestations; and though we cannot say that these outer cosmic influences are essentially nil, circumstances occur where it would be almost ludicrous to take account of them. Such was the experimenter's case who repeated my experiments on puncture of the floor of the fourth ventricle, to cause artificial diabetes: he thought that he exhibited greater accuracy in

carefully noting the barometric pressure at the moment of making the experiment. However, instead of experimenting on man and the higher animals, if we experiment on lower living beings, whether animal or vegetable, we shall see that the thermometric, barometric and hygrometric data, which were so unimportant in the first case, must on the contrary be kept very seriously under consideration in the second. Indeed, if we vary the conditions of humidity, heat and atmospheric pressure for infusoria, the vital manifestations in these beings are altered or annihilated according to the more or less significant variations that we make in the cosmic influences cited above. In vegetables and in cold-blooded animals, the conditions of t-emperature and humidity in the cosmic environment again play a very large part in the manifestations of life. This is what is called the influence of the seasons, which is familiar to everyone. In fine, then, only the warm-blooded animals and man seem to escape cosmic influences and to have free and independent manifestations. We have already said elsewhere that this kind of independence of vital manifestations in man and the higher animals results from greater perfection of their organism, but does not prove that manifestations of life in these physiologically more perfect beings are subject to other laws or other causes. We know, in fact, that the histological units of our organs express the phenomena of life; now if the functions of these units show no variations under the influence of variations in the temperature, humidity and pressure of the outer atmosphere, it is because they are immersed in an organic environment whose degrees of temperature, humidity and pressure do not change with variations in the cosmic environment. Hence, we must conclude that fundamentally manifestations of life in warm-blooded animals and in man are equally subject to exact and definite physico-chemical conditions.

In recapitulating all that we have already said, we see that conditions of environment in all natural phenomena govern their phenomenal manifestations. The conditions of our cosmic environment generally govern the mineral phenomena occurring on the surface of the earth ; but organized beings include within themselves the condition peculiar to their vital manifestations, and in proportion as the organism, i.e., the living machine, perfects itself, and its organized units grow more delicate, it creates conditions peculiar to an organic environment which becomes more and more isolated from the cosmic

environment. We thus come back to tlie distinction which I established long since, and which I believe very fruitful, to wit, that two environments must be considered in physiology: the general macrocosmic environment and the microcosmic environment peculiar to living beings ; the latter is more or less independent of the former, according to the degree of perfection of the organism. Moreover, we easily understand what we see here in the living machine, since the same thing is true of the inanimate machines created by man. Thus, climatic changes have no influence at all on the action of a steam engine, though everyone knows that exact conditions of temperature, pressure and humidity inside the machine govern all its movements. For inanimate machines we could therefore also distinguish between a macrocosmic environment and a microcosmic environment. In any case, the perfection of the machine consists in being more and more free and independent, so as to be less and less subject to the influence of the outer environment. The human machine is the more perfect, the better it defends itself from penetration by the influences of the outer environment; as the organism grows old and enfeebled, it becomes more sensitive to the outer influences of cold, heat, humidity, and in general to all other climatic influences.

To sum up, if we wish to find the exact conditions of vital manifestations in man and the higher animals, we must really look, not at the outer cosmic environment, but rather at the inner organic environment. Indeed, as we have often said, it is in the study of these inner organic conditions that direct and true explanations are to be found for the phenomena of the life, health, sickness and death of the organism. From the outside, we see only the resultant of all the inner activities of the body, which therefore seem like the result of a distinct vital force in only the most distant relations with the physico-chemical conditions of the outer environment, and manifesting itself always as a sort of organic personality endowed with specific tendencies. We have elsewhere said that ancient medicine considered the influence of the cosmic environment, of water, air and locality; we may indeed find useful suggestions here as to hygienic and as to morbid changes. But modem experimental medicine will be distinguished for being especially founded on knowledge of the inner environment where normal and morbid as well as medicinal influences take action. But how are we to know this inner

environment of the organism, so complex in man and in the higher animals, unless we go down and, as it were, penetrate into it, by means of experimentation applied to living bodies ? That is to say, to analyze the phenomena of life, we must necessarily penetrate into living organisms with the help of the methods of vivisection. To sum up, only in the physico-chemical conditions of the inner environment can we find the causation of the external phenomena of life. The life of an organism is simply the resultant of all its inmost workings; it may appear more or less lively, or more or less enfeebled and languishing, without possible explanation by anything in the outer environment, because it is governed by the conditions of the inner environment. We must therefore seek the true foundation of animal physics and chemistry in the physico-chemical properties of the inner environment. However, as we shall see further on, it is necessary to consider not only the physico-chemical conditions indispensable to life, but also the peculiar, evolutionary, physiological conditions which are the quid proprium of biological science. I have always greatly emphasized this distinction because I believe that it is basic, and that physiological considerations must predominate in a treatise on experimentation applied to medicine. Here indeed we shall find the differences due to influences of age, sex, species, race, or to state of fasting or digestion, etc. That will lead us to consider, in the organism, reciprocal and simultaneous reactions of the inner environment on the organs, and of the organs on the inner environment.

We have succeeded in discovering the laws of inorganic matter only by penetrating into inanimate bodies and machines; similarly we shall succeed in learning' the laws and properties of living matter only by displacing living organs in order to get into their inner environment. After dissecting cadavers, then, we must necessarily dissect living beings, to uncover the inner or hidden parts of the organisms and see them work; to this sort of operation we give the name of vivisection, and without this mode of investigation, neither physiology nor scientific medicine is possible ; to learn how man and animals live, we cannot avoid seeing great numbers of them die, because the mechanisms of life can be unveiled and proved only by knowledge of the mechanisms of death.

Men have felt this truth in all ages; and in medicine, from the earliest times, men have performed not only therapeutic experiments but even vivisection. We are told that the kings of Persia delivered men condemned to death to their physicians, so that they might perform on them vivisections useful to science. According to Galen, Attains III (Philometor), who reigned at Pergamum, one hundred thirty-seven years before Jesus Christ, experimented with poisons and antidotes on criminals condemned to death. ^ Celsus recalls and approves the vivisection which Herophilus and Erasistratus performed on criminals with the Ptolemies' consent. It is not cruel, he says, to inflict on a few criminals, sufferings which may benefit multitudes of innocent people throughout all centuries.^ The Grand Duke of Tuscany had a criminal given over to the professor of anatomy, Pallopius, at Pisa, with permission to kill or dissect him at pleasure. As the criminal had a quartan fever, Eallopius wished to investigate the effects of opium on the paroxysms. He administered two drams of opium during an intermission ; death occurred after the second experiment.* Similar instances have occasionally recurred, and the story is well known of the archer of Meudon who was pardoned because a nephrotomy was successfully performed on him. Vivisection of animals also goes very far back. Galen may be considered its founder. He performed his experiments especially on monkeys and on young pigs and described the instruments and methods used in experimenting. Galen performed almost no other kind of experiment than that which we call disturbing experiments, which consist in wounding, destroying or removing a part, so as to judge its function by the disturbance caused by its removal.

He summarized earlier experiments and studied for himself the effects of destroying the spinal cord at different heights, of perforating the chest on one side or both sides at once ; the effects of section of the nerves leading to the intercostal muscles and of section of the recurrent nerve. He tied arteries and performed experiments on the mechanism of deglutition.^ Since Galen, at long intervals in the midst of • Dezeimeris, Dicticmnaire historique, Vol. II, p. 444. Daremberg. Exposition des connaissances de Oalien sur Vanatomie pathologique et la pathologic du systeme nerveux. Thesis, 1841, pp. 13 and 80.

medical systems, eminent vivisectors have always appeared. As such, the names of Graaf, Harvey, Aselli, Pecquet, Haller, etc., have been handed down to us. In our time, and especially under the influence of Magendie, vivisection has entered physiology and medicine once for all, as an habitual or indispensable method of study. The prejudices clinging to respect for corpses long halted the progress of anatomy. In the same way, vivisection in all ages has met with prejudices and detractors. We cannot aspire to destroy all the prejudice in the world ; neither shall we allow ourselves here to answer the arguments of detractors of vivisection; since they thereby deny experimental medicine, i.e., scientific medicine. However, we shall consider a few general questions, and then we shall set up the scientific goal which vivisection has in view.

First, have we a right to perform experiments and vivisections on man? Physicians make therapeutic experiments daily on their patients, and surgeons perform vivisections daily on their subjects. Experiments, then, may be performed on man, but within what limits ? It is our duty and our right to perform an experiment on man whenever it can save his life, cure him or gain him some personal benefit. The principle of medical and surgical morality, therefore, consists in never performing on man an experiment which might be harmful to him to any extent, even though the result might be highly advantageous to science, i.e., to the health of others. But performing experiments and operations exclusively from the point of view of the patient's own advantage does not prevent their turning out profitably to science. It cannot indeed be otherwise; an old physician who has often administered drugs and treated many patients is more experienced, that is, he will experiment better on new patients, because he has learned from experiments made on others. A surgeon who has performed operations on different kinds of patients learns and perfects himself experimentally. Instruction comes only through experience ; and that fits perfectly into the definitions given at the beginning of this introduction.

May we make experiments on men condemned to death or vivisect them ? Instances have been cited, analogous to the one recalled above, in which men have permitted themselves to perform dangerous operations on condemned criminals, granting them pardon in exchange. Modem ideas of morals condemn such actions; I completely agree with these ideas ; I consider it wholly permissible, however, and useful to science, to make investigations on the properties of tissues immediately after the decapitations of criminals. A helminthologist had a condemned woman without her knowledge swallow larvae of intestinal worms, so as to see whether the worms developed in the intestines after her death. Others have made analogous experiments on patients with phthisis doomed to an early death ; some men have made experiments on themselves. As experiments of this kind are of great interest to science and can be conclusive only on man, they seem to be wholly permissible when they involve no suffering or harm to the subject of the experiment. For we must not deceive ourselves, morals do not forbid making experiments on one's neighbor or on one's self ; in everyday life men do nothing but experiment on one another. Christian morals forbid only one thing, doing ill to one's neighbor. So, among the experiments that may be tried on man, those that can only harm are forbidden, those that are innocent are permissible, and those that may do good are obligatory.

Another question presents itself. Have we the right to make experiments on animals and vivisect them? As for me, I think we have this right, wholly and absolutely. It would be strange indeed if we recognized man's right to make use of animals in every walk of life, for domestic service, for food, and then forbade him to make use of them for his own instruction in one of the sciences most useful to humanity. No hesitation is possible ; the science of life can be established only through experiment, and we can save living beings from death only after sacrificing others. Experiments must be made either on man or on animals. Now I think that physicians already make too many dangerous experiments on man, before carefully studying them on animals. I do not admit that it -is moral to try more or less dangerous or active remedies on patients in hospitals, without first experimenting with them on dogs; for I shall prove, further on, that results obtained on animals may all be conclusive for man when we know how to experiment properly. If it is immoral, then, to make an experiment on man when it is dangerous to him, even though the result may be useful to others, it is essentially moral to make experiments on an animal, even though painful and dangerous to him, if they may be useful to man.

After all this, should we let ourselves be moved by the sensitive cries of people of fashion or by the objections of men unfamiliar with scientific ideas? All feelings deserve respect, and I shall be very careful never to offend anyone's. I easily explain them to myself, and that is why they cannot stop me. I understand perfectly how physicians under the influence of false ideas, and lacking the scientific sense, fail to appreciate the necessity of experiment and vivisection in establishing biological science. I also understand perfectly how people of fashion, moved by ideas wholly different from those that animate physiologists, judge vivisection quite differently. It cannot be otherwise. Somewhere in this introduction we said that, in science, ideas are what give facts their value and meaning. It is the same in morals, it is everywhere the same. Facts materially alike may have opposite scientific meanings, according to the ideas with which they are connected. A cowardly assassin, a hero and a warrior each plunges a dagger into the breast of his fellow. What differentiates them, unless it be the ideas which guide their hands ? A surgeon, a physiologist and Nero give themselves up alike to mutilation of living beings. What differentiates them also, if not ideas ? I therefore shall not follow the example of LeGallois,^ in trying to justify physiologists in the eyes of strangers to science who reproach them with cruelty ; the difference in ideas explains everything. A physiologist is not a man of fashion, he is a man of science, absorbed by the scientific idea which he pursues : he no longer hears the cry of animals, he no longer sees the blood that flows, he sees only his idea and perceives only organisms concealing problems which he intends to solve. Similarly, no surgeon is stopped by the most moving cries and sobs, because he sees only his idea and the purpose of his operation.

Similarly again, no anatomist feels himself in a horrible slaughter house; under the influence of a scientific idea, he delightedly follows a nervous filament through stinking livid flesh, which to any other man would be an object of disgust and horror. After what has gone before we shall deem all discussion of vivisection futile or absurd. It is impossible for men, judging facts by such different ideas, ever to agree; and as it is impossible to satisfy everybody, a man of science should attend only to the opinion of men of science who understand him, and should derive rules of conduct only from his own conscience.

The scientific principle of vivisection is easy, moreover, to grasp. •LeGallois, (Euvrea. Paris, 1824. Preface, p. xxx. It is always a question of separating or altering certain parts of the living machine, so as to study them and thus to decide how they function and for what. Vivisection, considered as an analytic method of investigation of the living, includes many successive steps, for we may need to act either on organic apparatus, or on organs, or on tissue, or on the histological units themselves. In extemporized and other vivisections, we produce mutilations whose results we study by preserving the animals. At other times, vivisection is only an autopsy on the living, or a study of properties of tissues immediately after death. The various processes of analytic study of the mechanisms of life in living animals are indispensable, as we shall see, to physiology, to pathology and to therapeutics. However, it would not do to believe that vivisection in itself can constitute the whole experimental method as applied to the study of vital phenomena. Vivisection is only anatomical dissection of the living; it is necessarily combined with all the other physico-chemical means of investigation which must be carried into the organism. Reduced to itself, vivisection would have only a limited range and in certain cases must even mislead us as to the actual role of organs. By these reservations I do not deny the usefulness or even the necessity of vivisection in the study of vital phenomena. I merely declare it insufficient. Our instruments for vivisection are indeed so coarse and our senses so imperfect that we can reach only the coarse and complex parts of an organism. Vivisection under the microscope would make much finer analysis possible, but it presents much greater difficulties and is applicable only to very small animals.

But when we reach the limits of vivisection we have other means of going deeper and dealing with the elementary parts of organisms where the elementary properties of vital phenomena have their seat. We may introduce poisons into the circulation, which carry their specific action to one or another histological unit. Localized poisonings, as Fontana and J. Miiller have already used them, are valuable means of physiological analysis. Poisons are veritable reagents of life, extremely delicate instruments which dissect vital units. I believe myself the first to consider the study of poisons from this point of view, for I am of the opinion that studious attention to agents which alter histological units should form the common foundation of general physiology, pathology and therapeutics. We must always, indeed, go back to the organs to find the simplest explanations of life.