An Introduction to the Study of Experimental Medicine

To sum up, dissection is a displacing of a living organism by means of instruments and methods capable of isolating its different parts. It is easy to understand that such dissection of the living presupposes dissection of the dead. Anatomy is the basis necessary to all medical investigation, whether theoretical or practical. A corpse is an organism deprived of living motion, and the earliest explanation of vital phenomena was naturally sought in dead organs, just as we seek explanation of the action of a machine in motion by studying the parts of the machine at rest. It seems, therefore, that the anatomy of man ought to be the basis of physiology and human medicine. Prejudice, however, opposed dissection of corpses, and in default of the human body, men dissected corpses of animals, in organization as close as possible to man. Thus Galen's anatomy and physiology were done mainly on monkeys. At the same time, Galen also performed dissections of cadavers and experiments on living animals, thus proving that he understood perfectly that dissection of cadavers is significant only in so far as it is compared with dissection of living bodies. In this way, anatomy is indeed only the first step in physiology. Anatomy in itself is a sterile science; its existence is justified only by the presence of living men and animals, well and sick, and by its own possible usefulness to physiology and pathology.

We shall limit ourselves here to considering the kinds of service which anatomy, whether of man or of animals, in our present state of knowledge, can render physiology and medicine. This seems to me the more necessary, because different ideas on this subject hold sway in science ; in judging these questions it is, of course, understood that I take the point of view of experimental physiology and medicine, which together make up the truly active science of medicine. In biology we may accept various points of view which establish, as it were, just so many distinct sub-sciences. One science, in fact, is separate from another science only because it has a special point of view and a particular problem. In normal biology, we may distinguish the zoological point of view, the direct and comparative anatomical points of view, the special and the general physiological points of view. Zoology, describing and classifying species, is only

a science of observation used as a vestibule to the true science of animals. Tbe zoologist merely catalogues animals by outward or inner characteristics of form, according to the types and the laws which nature offers him in the formation of these types. The zoologists object is classification of beings according to a sort of plan of creation, and for him the problem is summed up in finding the precise place that an animal should fill in a given classification.

Anatomy, or the science of animal organization, is more closely and necessarily related to physiology. The anatomical point of view differs, however, from the physiological in this, that anatomists wish to explain anatomy by physiology, while physiologists seek to explain physiology by anatomy, which is quite another matter. The anatomical point of view has dominated science from the beginning up to the present, and it still has many partisans. The great anatomists who took this point of view all contributed valiantly, nevertheless, to the development of physiological science ; and Haller summed up the idea of the subordination of physiology to anatomy in defining physiology as anatomia animata. I can easily understand that the anatomical principle was destined necessarily to present itself first, but I believe that it is false in its limitations, and that it has to-day grown harmful to physiology, after having rendered great service, which I should be the last to deny. Anatomy, in fact, is a simpler science than physiology and consequently should be subordinate to it, instead of dominating it. Every explanation of vital phenomena, based exclusively on anatomical considerations, is necessarily incomplete. The great Haller, who summed up the anatomical period of physiology in his immense and admirable writings, restricted himself so far that his physiology is reduced to an irritable fibre and a sensitive fibre. The whole humoral or physico-chemical side of physiology, which cannot be approached by dissection and which treats of what we call our inner environment, was neglected. The reproach which I am making here against the anatomists who wished to subordinate physiology to their point of view, I make in the same way against chemists and physicists who wish to do the same thing.

They are also wrong in endeavoring to subordinate physiology, a more complex science, to chemistry or physics, which are simpler sciences. This has not prevented great service being rendered to physiology by much work in physiological chemistry and physics, even though conceived from a false point of view. In a word, I consider that the most complex of all sciences, physiology, cannot be completely explained by anatomy. To physiology, anatomy is only an auxiliary science, the most immediately necessary, I agree, but insufficient alone, unless we wish to assume that anatomy includes everything, and that the oxygen, chloride of sodium and iron found in the body are anatomical units of the body. Attempts of this kind have been revived in our day by eminent anatomists and histologists. I do not share these views, because they seem to me to create confusion in the sciences and to lead to darkness instead of light.

Anatomists, we said above, try to invert the true method of explanation, i.e., they take anatomy as an exclusive starting point, and propose to deduce directly from it all the functions solely by logic and without experiments. I have already protested against the pretentiousness of anatomical deductions,^ by showing that they rest on an illusion of which anatomists are unaware. In anatomy, we must in fact distinguish between two classes of things: (1) The passive mechanical arrangements of various organs and apparatus which, from this point of view, are really nothing but instruments of animal mechanics; (2) the activity of vital units which put in play this diverse apparatus. The anatomy of corpses can certainly take account of the mechanical arrangements of the animal organism; inspection of the skeleton certainly shows a combination of levers whose action we understand solely through their arrangement. So with the system of canals or of tubes conducting fluids; and thus the valves in the veins have mechanical functions which put Harvey on the track leading to the discovery of the circulation of the blood. The reservoirs, the bladders, the various pockets in which secreted and excreted fluids reside, offer mechanical arrangements which more or less clearly indicate the functions which they must fulfill, without our necessarily having recourse to experiment on the living to learn it. But we should notice that these mechanical deductions are by no means absolutely restricted to the functions of living beings; we deduce everywhere, in the same way, that pipes are meant to conduct, reservoirs meant to hold and levers meant to move.

When we come to the active or vital elements which put all the passive instruments of the organism in play, then anatomy of corpses cannot and does not teach anything. All our knowledge on this subject must necessarily come from experiment or from observation of the living ; when, therefore, anatomists believe that they are making deductions solely from anatomy and without experiments, they forget that their starting point was the same experimental physiology which they seem to disdain. When anatomists deduce the functions of an organism, as they say, from their texture, they merely use knowledge gained on the living, to interpret what they see in the dead; but anatomy really teaches them nothing, it merely supplies them with the quality of a tissue.

So when anatomists meet with muscular fibres in some part of the body, they infer contractile motion ; when they meet gland cells, they infer secretion ; when they meet with nerve fibres, they infer sensation or movement. But what taught them that muscular fibre contracts, that gland cells secrete, that a nerve is sensory or motor, unless it was observation of the living, or, in other words, vivisection ? Only, noting that these contractile, secreting or nerve tissues have definite anatomical forms, they establish a relation between the form of the anatomical unit and its functions, so that when they meet one, they infer the other. But, I repeat, dead anatomy teaches nothing; it merely leans on what experimental physiology teaches ; and a clear proof of this is that, where experimental physiology has learned nothing as yet, anatomists can interpret nothing by anatomy alone. Thus, the anatomy of the spleen, the suprarenal glands and the thyroid is as well known as the anatomy of a muscle or of a nerve, and nevertheless anatomists are silent as to the uses of these parts. But as soon as physiologists have discovered something about the functions of these organs, anatomists will put the physiological properties noted into relation with their anatomical observations. I must also point out that anatomists, in their localizations, can never go beyond the teachings of physiology, except under penalty of falling into error. Thus, if anatomists, on the basis of physiological teaching, suggest that, where muscular fibres are present, there are contraction and movement also, they may not infer that, where they see no muscular fibre, there is never contraction or movement. Experimental physiology has proved, in fact, that contracting units are of various forma, among them some which anatomists have not yet been able to define.

In a word, to know something about the functions of life, you must study them in the living. Anatomy yields only characteristics by which to recognize tissues, but itself teaches nothing about their vital properties. How indeed could the form of the nerve cell show us the nervous properties which it transmits ? How could the form of a liver cell show us that sugar is made in it ? How could the form of a muscle fibre teach us about muscular contraction? We have here only an empirical relation established by comparative observation of the living and the dead. I remember having often heard de Blainville try to differentiate in his lectures between what should be called, according to him, a substratum., and what should be called, on the other hand, an organ. In an organ, according to de Blainville, we should be able to understand the necessary mechanical relation between a structure and its function. Thus, from the form of bony levers, he said, we conceive a definite motion; from the disposal of the blood of the reservoirs for liquids, and of the excretory ducts of glands, we understand that liquids are put in circulation or retained by mechanical arrangements that we can explain. But as for the encephalon, he added, no material relations can be established between the structure of the brain and the nature of intellectual phenomena. Therefore, concluded de Blainville, the brain is not the organ of thought, it is merely a substratum. We may accept, if we like, de Blainville's distinction, but if so, it will be general and not limited to the brain. Indeed, if we understand that a muscle inserted between two bones may act mechanically as a power drawing them together, we by no means understand how the muscle contracts, and we can just as well say that the muscle is the substratum of contraction. Though we understand that a fluid secreted by a gland flows out of its tubes, we cannot thereby conceive any idea of the essence of secretory phenomena.

And we may just as well say that the gland is a substratum of secretion. To sum up, the anatomical point of view is wholly subordinate to the point of view of experimental physiology, as an explanation of vital phenomena. But, as we said above, there are two things in anatomy : the tools of the organism and the essential agents of life. The essential agents of life depend upon the vital properties of our tissues, which can be defined only by observation or by experiment on the living. These agents are the same in all animals, without distinction of class, genus or species. Here is the domain of general anatomy and physiology. Next come tools of life, which are nothing but mechanical tools or weapons with which nature especially provides each organism according to its class, its genus

or it8 species. We may even say that the special tools constitute the species; for a rabbit differs from a dog only because one has organs that make it eat grass, and the other organs that force it to eat flesh. But as to the inmost phenomena of life, the two animals are identical. A rabbit is carnivorous if we give him meat ready prepared, and I long ago proved that all fasting animals are carnivorous. Comparative anatomy is merely an inner zoology; its aim is to classify the apparatus or' tools of life. These classifications should corroborate or rectify the characteristics suggested by outer forms. Thus the whale, which naight be put with the fishes by reason of its outer form, is placed with the mammals because of its interior organization. Comparative anatomy shows us also that the tools of life are arranged in necessary and harmonious relations with the whole organism. Thus, an animal with claws should have the jaws, teeth and the articulations of the limbs disposed in a definite way. The genius of Cuvier amplified these views and derived from them a new science, paleontology, which reconstructs an entire animal from a fragment of his skeleton. The object of comparative anatomy, then, is to show the functional harmony of the tools with which nature has endowed an animal and to teach us the changes necessary in these tools according to various circumstances of animal life. But beneath all these changes comparative anatomy always shows us the uniform plan of creation; thus any number of organs exist, not as aids to life (they are often actually harmful), but as characteristics of the species or as vestiges of a single plan of organic composition. The stag's antlers have no use favorable to the animal's life; the shoulder blade of a slow-worm and the mammae in males are vestiges of organs that have lost their functions. Nature, as Goethe said, is a great artist; to ornament forms, she often adds organs that are useless to life in itself, as an architect makes ornaments for his building, such as friezes, cornices and volutes which are useless for habitation.

The object of comparative anatomy and physiology is, therefore, to find the morphological laws of the tools and the organs which together make up organisms. Comparative physiology, in so far as it infers functions by comparing organs, would be an insufficient and false science if it rejected experimentation. Comparing the forms of limbs or of the mechanical apparatus of life may suggest the uses of these parts. But what can the form of the liver or the pancreas tell

us about the function of these organs ? Has not experiment shown the mistake of likening the pancreas to a salivary gland ? What can the form of the brain or the nerves teach us about their functions ? All that we know has been learned by the observation of the living, or by experiment. What can we say about fishes' brains, for instance, until experiment has clarified the question? In a word, anatomical deduction has yielded what it can. To linger in this path means lagging behind the progress of science and believing that we can impose scientific principles without experimental verification. That, in a word, is a relic of the scholasticism of the Middle Ages. But, on the other hand, comparative physiology, in so far as it relies on experiment and seeks the properties of tissues and organs in animals, does not seem to me to have separate existence as a science. It falls back necessarily into special or general physiology, since its object is the same.

We distinguish between the various biological sciences only by the goal which we set ourselves or the idea which we pursue in studying them. Zoologists and comparative anatomists see all living beings as a whole, and by studying the outer and inner characteristics of beings, they seek to discover the morphological laws of their evolution and their transformation. Physiologists take a quite different point of view : they deal with just one thing, the properties of living matter and the mechanism of life, in whatever form it shows itself. For them, genus, species and class no longer exist. There are only living beings ; and if they choose one of them for study, that is usually for convenience in experimentation. Physiologists also follow a different idea from the anatomists. The latter, as we have seen, try to infer the source of life exclusively from anatomy ; they therefore adopt an anatomical plan. Physiologists adopt another plan and follow a different conception ; instead of proceeding from the organ to the function, they start from the physiological phenomenon and seek its explanation in the organism. To solve the problem of life, physiologists therefore call to their aid all the sciences, — anatomy physics, chemistry, which are all allies serving as indispensable tools for investigation. We must, therefore, necessarily be familiar enough with these various sciences to know all the resources which may be drawn from them. Let us add, in ending, that from every

" Claude Bernard, Memoire sur le pancreas. ( Supplement au(c Comptes rendus de VAcademie des sciences. 1856. Vol. I.) biological point of view, experimental physiology is in itself the one active science of life, because by defining the necessary conditions of vital phenomena it will succeed in mastering them and in governing them through knowledge of their peculiar laws. What we said in the last paragraph about normal anatomy and physiology may be repeated for pathological anatomy and physiology. We find similarly three points of view appearing one after another, the taxonomical or nosological point of view, the anatomical point of view and the physiological point of view. We cannot here go into detailed study of these questions, which would include neither more nor less than the entire history of medical science. We shall limit ourselves to suggesting our idea in a few words.

While observing and describing diseases, men must have sought at the same time to classify them, as they sought to classify animals, and according to precisely the same principles, by artificial or natural methods. Pinel applied to pathology the natural classification introduced into botany by de Jussieu, and into zoology by Cuvier. It is sufficient to quote the first sentence of PineFs Nosography : "Given a disease, to find its place in a nosological scheme." No one, I think, will consider this the goal of all medicine ; it is merely a partial point of view, the taxonomic point of view.

After nosology came the anatomical point of view ; that is, after considering diseases as morbid species, men try to place them anatomically. It was thought that, just as there is a normal organization to take account of vital phenomena in the normal state, so there must be an abnormal organization to take account of morbid phenomena. Though the point of view of pathological anatomy can already be recognized in Morgagni and Bonnet, still it is especially in this century, under the influence of Broussais and Laennec, that pathological anatomy has been systematically built up. Men compared the anatomy of diseases, they classified changes in tissues, but they also tried to bring these changes into relation with the morbid phenomena and, as it were, to deduce the second from the first. The same problems presented themselves as in comparative, normal "Pinel, Nosographie philosophique. 1800.

anatomy. In the case of morbid changes producing physical or mechanical alteration in a function, as for instance a vascular compression or mechanical lesion of a limb, men could understand the relation connecting the morbid symptom with its cause and could make what is called a rational diagnosis. Laennec, one of my predecessors in the chair of medicine at the College de France, immortalized himself in this field by the precision which he gave to physical diagnosis of diseases of the heart and lungs. But diagnosis became impossible in the case of diseases where changes were imperceptible with our present means of investigation. 'No longer able to find an anatomical relation, men said then that the disease was essential, i.e., without any lesion; which is absurd, for it amounts to acknowledging an effect without a cause. Men came to understand that, to find the explanation of such diseases, they must carry their investigations into the minutest parts of the organism where life has its seat. The new era of microscopic pathological anatomy was inaugurated in Germany by Johannes Miiller; and an illustrious professor in Berlin, Virchow, recently systematized microscopic pathology. -^^ So in changes of the tissues, they found proper characteristics for defining diseases. A propos of this, they invented the name pathological physiology, to designate pathological function in relation to abnormal anatomy. I shall not have to consider whether these expressions, pathological anatomy and physiological pathology, are well chosen. I shall simply say that the pathological anatomy, whose pathological phenomena they define, is subject to the same objection of insufficiency that I have already made to normal anatomy.

First, the pathological anatomists assume it proved that anatomical changes are always primary, which I do not admit, believing the contrary, that a pathological change is very often secondary and is the consequence or fruit of the disease instead of its germ ; which does not prevent this product from later becoming a morbid germ of other symptoms. I shall therefore not admit that cells or fibres of tissues are always primarily attacked; a morbid physico-chemical change in the organic environment being able, in itself, to lead to the morbid phenomena, in the manner of a toxic symptom which occurs, without

" Miiller, De Olandularum secernentium structura penitiori earumque prima formatione in homine atque animalihus. Leipzig, 1830. "Virchow, La Pathologic cellulaire basee sitr Vitude physioloyique et pathologique des tissus, translated by P, Picard. Paris, 1860. primary lesion of the tissues, through mere change in the environment. The anatomical point of view is therefore insufficient, and the changes noted in cadavers after death really show characteristics by which to recognize and classify diseases, rather than lesions capable of explaining death. It is indeed strange to see how little attention most physicians pay to this latter point of view, which is the true point of view of physiology. When a physician, for example, makes a typhoid autopsy, he notes the intestinal lesions and is satisfied. But in reality that explains absolutely nothing about either the cause of the disease, or the action of drugs, or the reason for death. Microscopic anatomy teaches us no more about it, for when a person dies of tuberculosis or pneumonia or typhoid fever, the microscopic lesions found after death existed before, and often long before ; death is not explained by the particles either of the tubercle or of Peyer's patches in the intestines or of other morbid products ; death, in fact, can be understood only because some histological unit has lost its physiological properties, a loss which has brought on the disruption of vital phenomena. But to grasp the physiological lesions in their relations with the mechanism of death, we should have to make autopsies on cadavers immediately after death, which is impossible. This, then, is why we must perform experiments on animals and must necessarily give medicine the experimental point of view, if we mean to found a truly scientific medicine which shall logically embrace physiology, pathology and therapeutics. For many years I have done my best to advance in this direction.^* But the point of view of experimental medicine is most complex, in that it is physiological and also includes explanation of pathological phenomena by anatomy.

A propos of pathological anatomy, I shall repeat what I said about normal anatomy, to wit, that anatomy in itself teaches nothing without observation of the living. For pathology we must therefore establish pathological vivisection, that is to say, we must create diseases in animals and sacrifice them at various stages of these diseases. We may also study in the living the changes in the physiological properties of tissues as well as the changes in the cells or the environments. When the animal dies, we must make an autopsy immediately after death, just as if we were dealing with one of those instantaneous diseases called poisoning, for fundamentally

"Claude Bernard, Cours de pathologic e(cp4rimentale. {Medical Times, 1860.) there is no difference in the study of physiological activities, whether morbid, toxic or medicinal. In a word, a physician should not hold to anatomical pathology alone, to explain the disease ; he starts from observation of the patient and later explains the disease by physiology with the help of pathological anatomy and all the allied sciences used by investigators of biological phenomena.

VI. The Variety of Animals Subjected to Experimentation ; THE Variability of Organic Conditions Which They Present to Experimenters All animals may be used for physiological investigations, because, with the same properties and lesions in life and disease, the same result everywhere recurs, though in mechanism the vital manifestations vary greatly. However, the animals most used by physiologists are those procured most easily, and here we must set in the front rank domestic animals such as dogs, cats, horses, rabbits, oxen, sheep, pigs, barnyard fowl, etc., but if we had to reckon up the services rendered to science, frogs would deserve the first place, l^o other animal has been used for greater or more numerous discoveries, at all points in science ; and even to-day, physiology without frogs would be impossible. If the frog, as has been said, is the Job of physiology, that is to say, the animal most maltreated by experimenters, it is certainly the animal most closely associated with their labors and their scientific glory. To the list of animals cited above, we must add many others, warm-blooded and cold-blooded, vertebrates and invertebrates, and even infusoria which may be used for special investigations. But specific diversity is not the sole difference between the animals which physiologists subject to experimentation; in the condition in which they are found, they present many differences which at this point require consideration; for without knowledge or appreciation of their individual characteristics, we can have neither biological exactness nor precision in experimentation.

The first condition for making an experiment is that its circumstances must be so well known and so precisely defined that we can always reconstruct them and reproduce the same phenomena at will. We have said elsewhere that this fundamental condition of " C. Dumeril, Notice historique sur les decouvertes\ faites dans les sciences d'ohservation par Vetude de Vorganisme des grenouilles. 1840. experimentation is relatively easy to fulfill in inorganic beings and is surrounded with great difficulties in living beings, particularly in warm-blooded animals. In fact, we must not only reckon with variations in the surrounding cosmic environment, but must also reckon with variations in the organic environment, — that is to say, the present state of the animal organism. We should therefore be greatly in the wrong if we believed it enough, in making an experiment on two animals of the same species, to place them in exactly the same experimental conditions. In every animal, certain physiological conditions of the inner environment have an extreme variability, which, at a given moment, produces appreciable differences, from the experimental point of view, between animals of the same species whose outward appearance is identical. I believe that, more than anyone else, I have emphasized how necessary it is to study physiological conditions, and have shown that knowledge of them is the necessary foundation of experimental physiology.

We must indeed admit that vital phenomena in an animal vary only with precise and definite conditions of the inner environment. We shall therefore try to find these experimental, physiological conditions, instead of tabulating the variations in phenomena and taking averages as expressions of reality ; we should thus reach conclusions based on correct statistics, but with no more scientific reality than if they were wholly arbitrary. If we wish to wipe out the diversity evident in organic fluids by taking the averages of all the analyses of urine or blood, even from an animal of the same species, we should thus have a mere combination of these humors corresponding to no definite physiological state of the animal. I have indeed shown that, in fasting, urine always has the same definite composition ; I have shown that the blood coming out of an organ is quite different, according to whether the organ is in a state of activity or rest. If we look for sugar in the liver, for instance, and make tabulations of its absence or presence, and take averages to find out how many times per hundred there is sugar or glycogen in that organ, we shall find a number which, whatever it is, means nothing, because, as I have shown, in certain physiological conditions there is always sugar, and in other conditions there is never any. Now taking another point of view, if we meant to consider all the experiments successful in which there was hepatic sugar and consider all those unsuccessful in which there was none, we should fall into another but no

less reprehensible kind of error. In fact, I have posited this principle: there never are any unsuccessful experiments; they are all successful in their own definite conditions, so that negative cannot nullify positive results. I shall return elsewhere, however, to this important subject. For the moment, I wish merely to call to the attention of experimenters the importance of defining organic conditions, because, as I have already said, they are the one foundation of experimental physiology and medicine. In what follows, a few indications will suffice, since those conditions will be studied later, d propos of each particular experiment, from the three points of view : physiological, pathological and therapeutic.

In every experiment on living animals, three kinds of physiological conditions peculiar to the animal must be considered, apartfrom general cosmic conditions, to wit: anatomical operative conditions, physico-chemical conditions of the inner environment and organic conditions of units in the tissues. 1. Operative Anatomical Conditions. — Anatomy is the necessary foundation of physiology, and never can we become good physiologists if we are not first deeply versed in anatomical studies and trained in delicate dissections, so as to be able to make the preparations which are often required for physiological experiments. In fact, operative anatomical physiology has not yet been founded; the zoologists' comparative anatomy is too vaguely superficial for physiologists to find in it the exact topographical knowledge that they need ; the anatomy of domestic animals is done by veterinarians from too special and restricted a point of view to be of great use to experimenters, and thus physiologists are ordinarily reduced to making for themselves the anatomical investigations which they need to devise their experiments. It is evident that, in severing a nerve, tying a duct or injecting a vessel, knowledge of the anatomical arrangement of parts, in the animal operated on, is absolutely indispensable to understanding and defining the physiological results of the experiment. Some experiments would be impossible with certain species of animals, and intelligent choice of an animal offering a happy anatomical arrangement is often a condition essential to the success of an experiment and to the solution of an important physiological problem. Anatomical arrangements may sometimes present anomalies which must also be thoroughly known, as well as the variations observed between one animal and another. In the sequel of this

work, I shall therefore be careful always to describe experimental methods, including the anatomical arrangement, and I shall show that divergencies of opinion among physiologists have been caused, more than once, by anatomical differences which they failed to reckon with, when interpreting the results of experiments. As life is merely a mechanism, anatomical arrangements peculiar to certain animals may seem insignificant at first sight ; yet these seemingly futile minutiae are often enough to change the physiological manifestations completely and to form what we call a highly important idiosyncrasy. A case in point is section of the two facial nerves, which is mortal in horses, but not mortal in other closely related animals.

2. Physico-chemical Conditions of the Inner Environment. — Life is made manifest by the action of outer stimuli on irritable living tissues which react by manifesting their special properties. The physiological conditions of life are therefore nothing but the special physico-chemical stimuli which set in action the tissues of the organism. These stimuli are found in the atmosphere or the environment which the animal inhabits ; but we know that the properties of the general outer atmosphere pass into the organic atmosphere in which all the physiological conditions of the outer atmosphere are found, plus a certain number of others peculiar to the inner environment. We shall content ourselves here with naming the principal physico-chemical conditions of the inner environment to which experimenters should direct their attention. These, moreover, are only the conditions oifered by every environment in which life manifests itself.

Water is the first indispensable condition of every vital manifestation, as of every manifestation of physico-chemical phenomena. In the outer cosmic environment we may distinguish between aquatic and aerial animals; but this distinction can no longer be made between histological units ; plunged in the inner environment, they are aquatic in all living beings, that is to say, they are bathed in organic fluids, including very large quantities of water. The proportion of water at times reaches 90 to 99 per cent, in the organic fluids, and when this proportion of water is notably diminished, peculiar physiological troubles result. Thus, if we remove water from frogs by prolonged exposure to dry air, and if we reduce the quantity of water in the blood by introducing into the body substances with a very high endosmotic equivalent, we witness convulsive phenomena, which