Side by side with the development of physics and chemistry on the lines laid down by physicists and chemists from the time of Galileo onwards, there grew up a very fruitful and practically useful development in the application of physical and chemical conceptions to various phenomena observed in living organisms. This latter development originated with the rise of anatomy in the sixteenth century, and has been continued since then in the interpretation of observations on living or dead animals, plants, or men. We can trace this development throughout the progress of physiology up to the present day.
In view of the success attained in this direction it was only natural that attempts should be made to reach forward towards a complete mechanistic or physico-chemical conception of all the phenomena of what can be described as mere life. As is well known, such an attempt was made by Descartes in the seventeenth century. This attempt was one of extraordinary significance. The leadership of Descartes has been recognized on all hands by those who have subsequently maintained that the proper line to take in the study of biology is to aim at a complete physico-chemical account of the phenomena of life, thus placing biology in the position of a branch of physics and chemistry.
The attempt of Descartes is contained in his two short books De Homine and De Formatione Foetus. The aim of these books was to show that life may, in so far as it is not deliberately directed by the soul, be regarded as consisting of mechanical or physico-chemical processes, the living body itself being also produced from its material elements by mechanical processes. As regards the details of these processes, he says that they may be different from what he suggests, and that his only concern was to demonstrate that they may be regarded as mechanical processes of some sort. Thus his general argument was in no way compromised by the subsequent demonstration that many of the particular mechanical processes which he hypothetically suggested are non-existent. He had put forward a general hypothesis as to the nature of life, and this hypothesis has gained very widespread support. To many scientific men of the present time, and to a multitude of popular writers, its truth seems, indeed, to be self-evident.
Even in the time of Descartes it was already clear that much of what occurs within the living body is susceptible of clear mechanical explanation. Thus the movements, whether voluntary or involuntary, of the limbs, etc., had been rendered intelligible by showing how, when muscles contract, the tendons attached to them act on the bones to which they are also attached, thus bringing about mechanically the various voluntary and involuntary movements of the bodily parts attached to these bones. Kepler had shown how the crystalline lens of the eye, acting just like a glass lens, produces an image on the retina. Harvey had shown how the blood, driven mechanically by pressure from the heart, and guided by valves, is circulated round the body, carrying nutriment to and removing waste products from all parts. No one questioned successfully the mechanical explanations applied in connexion with these and various other processes occurring within the living body. It therefore seemed natural enough to adopt the belief that all physiological processes are ultimately susceptible of similar mechanical or physico-chemical explanation. In the present and succeeding lecture I shall attempt to follow out the manner in which this belief has developed side by side with the advance of knowledge as to the facts of physiology and organic morphology.
The suggestions of Descartes as to the possible details of a mechanistic physiology applicable to the living bodies of men and higher animals were largely based on the discovery of the circulation of the blood. He supposed that in the development of the embryo the first thing formed is a rudimentary beating heart. He also assumed, regardless of the teaching and experiments of Harvey, that the active phase in the beating of the heart is the diastole. He regarded the diastole as an act of swelling or effervescence due to chemical action, the systole being merely a return of the heart to its natural size as blood escaped from it into the arteries and the effervescence died away. He also suggested that the embryonic heart and blood-vessels are perforated by a very large number of minute holes, through which material is forced out, which on becoming partially solidified forms the various fibres of which the structure of the adult body consists, the different sizes and shapes of these fibres being determined by the different sizes and shapes of the holes.
He supposed that the lighter parts of the blood projected from the heart tend to pass upwards, finally reaching the choroid plexus of the brain in a very attenuated state. This attenuated fluid then escapes into the first pair of ventricles, and constitutes the “animal spirit.” When the animal spirit passes down the tubules assumed to exist in motor nerve-fibres, contraction of the corresponding muscles is produced by the distension of the muscles, which were also assumed to be hollow. The passage of the animal spirit down the nerve-tubules was supposed to be controlled by valves at their upper openings, and the valves in their turn were controlled by the afferent nerve-fibres passing from the surfaces of the body to the ventricles. Thus any sensory disturbance of the skin or sense-organs was responded to by an opening of certain valves, and consequent distension and contraction of muscles, this being a purely mechanical reflex response. All the other physiological processes in the body were supposed to occur also by various purely mechanical or chemical processes.
The soul itself was supposed to have its seat in the pineal gland, between the ventricles, and could contemplate the various reflex nervous responses, and to some extent control them by altering the inclination of the gland towards the valves. At this point, however, the physiology of Descartes became very vague, and it seems evident that the body could be conceived as working quite well without any interference from the soul. He in fact regarded the bodies of animals as acting mechanically and quite unconsciously; and the manner in which body and soul were connected in the case of men was in reality unintelligible, and became a fruitful source of contention among his successors.
It is easy to see how amazingly crude and ill-founded most of the details of the physiology of Descartes were; but he had at least sketched out the possible outlines of a thorough-going mechanistic physiology. For this he deserves full credit. How certain of these outlines were more correctly filled in by his successors we can now proceed to describe.
The weakest feature in the Cartesian physiology was the embryology. This was not based on any definite observations; but even if it had been it would have given no account whatever of the original formation of the heart and of the elaborate and very definite system of peculiarly shaped holes in its walls which were assumed by the theory. Perhaps the most plausible theory suggested by the mechanistic successors of Descartes was that the germ contains a complete model of the developed organism, so that all which occurs in development is a process of growth of this model, not associated with any increase in its structural complication. This, however, merely threw the problem back a stage, and did not simplify it in any way; nor is there any direct evidence in support of such a theory, which, indeed, was mainly a sop to current theological beliefs. All the anatomical and microscopical evidence is conclusively against it.
The problem of reproduction has hitherto remained an inscrutable one for the mechanistic theory of life. Our knowledge of the appearances which may be observed during all the stages of reproduction has increased enormously since Descartes wrote his De Formatione Foetus; but anything of the nature of a mechanistic theory of reproduction is still absent, as we shall see. In other directions, however, we can follow quite clearly the development of the mechanistic physiology.
For Descartes chemical processes occurring in the heart as a result of the mixture of different kinds of blood entering it were the source of all kinds of bodily activity, and of animal heat. The outlines, at least, of a far more satisfactory chemical theory were produced by the Oxford School of physiologists in the seventeenth century, shortly after Descartes wrote. By his experiments on animals subjected to a vacuum Boyle showed that air, and not merely breathing, is necessary to their life, as well as to ordinary combustion. Mayow then showed that it is only a certain constituent of air that is necessary in both cases, and connected this constituent with what is present in nitre and enables combustion to occur, as in gunpowder, without the presence of air. He called this constituent “nitro-aerial spirit,” and put forward the theory that nitro-aerial spirit is absorbed from the air by the blood passing through the lungs, and separated from it in the brain in some such manner as Descartes had suggested; also that muscular contraction is due to an explosive combination in the muscles of nitro-aerial spirit and combustible material, with evolution of heat, the nitro-aerial spirit being allowed to pass down nerve-tubules and so reach the muscles.
This theory was a great advance on that of Descartes. It was not only consistent with Harvey's observations on the heart, but it definitely connected chemical processes outside the body with those occurring within it. It also connected muscular work with the increased breathing and increased heat production which accompany it, besides affording, just as the theory of Descartes did, an explanation of why section or ligature of a motor nerve causes paralysis of muscular movement. The contraction of the heart itself was now also regarded as an ordinary example of muscular contraction; and Lower, another member of the Oxford School, demonstrated the stoppage or disorganization of the heart-action on ligature of the vagus nerves going to the heart. This he attributed to interference with the supply of nitro-aerial spirit to the heart. He had in reality discovered what is now known as inhibition of the heart by stimulation of the vagus nerve.
Unfortunately the active study of physiology and most other branches of natural science was allowed to die out for nearly two centuries at Oxford. The early Oxford physiologists and chemists had practically discovered oxygen and its direct connexion with muscular work; but their work was forgotten, and it was not till 1845 that the direct connexion between muscular work and consumption of oxygen was finally pointed out by Mayer.
Meanwhile Descartes's theory of muscular contraction had been attacked from other sides. It was shown experimentally by Glisson of Cambridge that muscles do not increase in volume when they contract, as they would do on the theory of Descartes, and the contraction of all muscles, including the heart, came to be attributed to a property inherent in them, and called excitability or irritability. Harvey's experiments had shown clearly that it is the heart-muscle itself which contracts actively and produces the circulation. Further investigation showed more and more clearly that all muscular structures are excitable independently of any immediate source of their energy from their physical or chemical surroundings; and the same conception was extended to nervous structures. For a considerable time, therefore, mechanistic developments in physiology did not make any further progress in connexion with muscular and nervous activity.
Mechanistic speculation was meanwhile not absent in other directions. Secretion by the kidneys and other glands was generally attributed to a mechanical process of filtration through very narrow pores, insufficiently large to permit the passage of blood-corpuscles; and owing to absence of knowledge of the chemical composition of these secretions and of the blood, these crude theories passed muster to a considerable extent, together with similar theories as to absorption from the intestine.
With the great development of chemistry towards the end of the eighteenth century mechanistic developments in physiology became more definite. The rediscovery by Priestley of identity in the chemical changes in respiration and in ordinary combustion, and more particularly Lavoisier's clear physical interpretation of what occurs in oxidation, whether inside or outside the body, were great steps forward. When, moreover, Lavoisier and Laplace showed experimentally that the heat produced by oxidation in the living body corresponds in amount with that produced by oxidation or combustion of carbonaceous material outside the body, a mechanistic explanation of the production of animal heat seemed to be reached.
On the discovery of the chemical composition of various food materials in the early nineteenth century there followed the definite identification of diastase, pepsin, and other enzymes or unorganized ferments. This brought to the front a purely chemical theory of digestion, and at the same time proved the existence of a class of chemical bodies capable of inducing otherwise unintelligible chemical changes within the living substance of the body.
Another very important step made early in the nineteenth century was the publication by Schwann in 1839 of his conclusion that the bodies of the higher animals are made up of the units which he, following Schleiden, who had made the corresponding discovery for the bodies of plants, called cells. This discovery was generally interpreted as showing that, whatever the nature of life may be, the processes occurring in any organ of an animal are nothing but the sum of those independently occurring in cells of the organ, while what occurs in the body as a whole is likewise only the sum of what occurs in its constituent cells. Subsequent investigation seemed to confirm in every respect the general conception of the body of any higher animal as a collection of a vast number of cell units; and this in itself appeared to be an important step towards a mechanistic conception of life.
From his microscopical observations Schwann drew the further conclusion that cells are formed from a mother liquid by a physical process akin to crystallization. This theory was a very definite attempt in the direction of a mechanistic theory of reproduction, and was at any rate somewhat less crude than the attempt of Descartes. Further investigation showed, however, that new cells are only produced by a process of division of pre-existing cells. At no step in the process of reproduction are we dealing with anything which we can interpret as non-living; and the reason why organisms reproduce their like remained as dark as ever from a physico-chemical standpoint. Thus Schwann's attempt at a mechanistic theory of reproduction failed as completely as that of Descartes.
Schwann was one of the senior leaders in a determined attempt, shared in by almost all the younger physiologists of his time, to get rid of what was known as vitalism in physiology. The celebrated physiologist and comparative anatomist Johannes Müller, whose assistant he was, supported vitalism strongly; but nearly all Müller's other assistants and pupils, including du Bois Reymond, Helmholtz, Ludwig, and Brücke, followed Schwann in rejecting vitalism and concluding that it is only along physico-chemical lines that real scientific progress can be looked for in physiology. This movement soon became general among physiologists in all European countries.
Schwann himself was an orthodox Catholic, and afterwards became a professor at the very orthodox Catholic university of Louvain. Like Descartes, and like many theologians, including for instance Paley, author of a well-known book on the arguments from design, Schwann believed that the living body itself is nothing but a physico-chemical machine, though in conscious action this machine is guided by the soul. Most of his physiological contemporaries, however, adopted a more thorough-going mechanistic standpoint, and concluded that whether or not consciousness accompanies the activity of the living body, it acts and must act as nothing but a physico-chemical mechanism, however difficult it may be to see in detail how the action is brought about.
This conclusion furnished a clear and intelligible working hypothesis in physiology, and continued for long to satisfy the great majority of workers in physiology. Experience seems always to show that if we investigate any physiological phenomenon we can discover by experiment some physical condition which can be interpreted as its cause, even though the precise connexion between the effect and the cause is still obscure. The presence, for instance, of moisture, warmth, or oxygen can be shown to be essential to physiological processes, or even to consciousness; and evidence of the same kind is constantly being added to as physiological knowledge advances.
A great stimulus to mechanistic physiology was afforded by the application to physiological phenomena of the principle of conservation of energy. This principle was first stated in general terms in 1842 by Mayer, a German country doctor. It was applied by him specifically to physiological phenomena in his book Die organische Bewegung in ihrem Zusammenhange mit dem Stoffwechsel, published in 1845, and was stated still more clearly two years later, by Helmholtz, then a young army doctor who was working in Johannes Müller's laboratory. It was now possible to trace back to potential chemical energy the energy which manifests itself in muscular work and other forms of vital activity. Not only animal heat, but also the energy manifested in muscular work, nervous activity, etc., could thus be interpreted as having its source in the fact that oxygen and oxidizable substances produce in their combination kinetic energy, in virtue of their potential energy in the uncombined state. By measuring the consumption of oxygen, production of resulting products, and liberation of kinetic energy, whether inside or outside of the body, it could be shown that the new interpretation was in complete accordance with physiological observation. The more accurate the observations and measurements the more complete did the accordance appear, although, as already mentioned, it was not till 1893 that extremely close accordance between the potential energy of oxidation and the total kinetic energy liberated within the body was finally demonstrated by Rubner. As to how exactly the various forms of energy are transformed in living organisms we are still very much in the dark; but it had at least become possible to state in physico-chemical terms the sources of the energy liberated or stored up in the bodies of living organisms, whether animals or plants, as well as the sources of the material present.
For Schwann and his early contemporaries the cell was a structure with a membranous wall, containing a liquid or plasma and a nucleus, the liquid being interpreted as a solution containing albumin. Botanical observation showed, however, that the liquid could often be distinguished into two parts, one of which behaved like an ordinary liquid, whereas the other showed what seemed to be independent movement, and came to be distinguished on v. Mohl's proposal as “protoplasm,” since it, along with the nucleus which was contained in it, appeared to be the most primitive part of the cell, and was always present in cells showing signs of life, though the other liquid might be absent. Observations on animal cells showed also that the protoplasm and nucleus were the essential parts of a cell, other parts of cells being mere derivations from or else modification of the protoplasm. In pathology, under the vigorous lead of Virchow, various forms of abnormal structure were shown to be due to cell-proliferation.
In physiology there was a corresponding movement towards making the protoplasm the essential seat of active physiological processes, and moreover ascribing to this protoplasmic activity a large amount of apparent independence of immediate changes in the environment. Protoplasm in some form thus became the seat of the “excitability” so long known to physiologists.
We can, for instance, trace this new standpoint in the investigations of Pflüger on physiological oxidations. It had been shown by previous investigations that the blood passing through the lungs takes up oxygen in loose chemical combination with the haemoglobin of the blood-corpuscles, and also takes up carbon dioxide, as it is formed within the body, in somewhat similar loose combination with alkaline substances in the blood. Ludwig, and particularly Pflüger, had immensely improved the method of separating by means of the mercurial vacuum pump the gases of the blood for analysis. It had been very generally believed hitherto that the oxidation on which heat-production depends is carried out to a large extent in the blood; and indeed Ludwig and his pupils had brought some evidence pointing apparently in this direction. It was also very generally believed that the rate of oxidation, as in ordinary oxidation processes outside the body, must vary with the amount of oxygen brought to the blood by breathing. This teaching is, for instance, very clearly expressed in Liebig's writings.1
With his improved methods Pflüger showed very clearly that no appreciable amount of oxidation occurs in the blood itself, but that practically all of it occurs inside the living cells; also that the rate of oxidation is within considerable limits independent of the concentration of oxygen in the blood or blood-plasma. He thus showed that “the living cell regulates its own oxidation processes.” Pflüger was no vitalist, though this quotation from him savours somewhat of vitalism; but he played a large part in the movement towards centring the elementary problems of physiology within the substance of living cells.
Another example of the same movement in physiology concerned the manner of regarding the consumption of material, or general metabolism of the body. Liebig treated the rate of consumption of non-living material in the body as dependent, on the one hand on the supply of food material, and on the other on the supply of oxygen. This would naturally be the case if the oxidation occurred in ordinary liquids existing within the body. In order to be able to measure the amount of albuminous material oxidized in the body he introduced a method for determining the urea in urine, since it was already known that none of the nitrogen of albuminous material leaves the body in the gaseous form, and it was apparent that nearly all of it must be excreted as urea. It was found that the excretion of urea went up and down with variation in the supply of albuminous material as food, though even after starvation for some time a certain minimum amount of urea continued to be excreted.
Other physiologists, and particularly Bidder and Schmidt, and Voit, now, however, proceeded to investigate the total metabolism, both of oxygen and carbon dioxide and of nitrogenous material. As soon as the gaseous exchange was determined it became evident that the excretion of urea was no real measure of the essential vital metabolism; for when the oxidation of albuminous material was cut down, the oxidation of fat and carbohydrate, as calculated from the respiratory exchange, increased, and after starvation for some time nearly the whole of the oxidation was of fat. Thus the body maintains its oxidation by substituting fat or carbohydrate for albumin when the latter is less readily available.
The investigations of Rubner finally showed that when proper experimental precautions are taken, albumin, carbohydrate, and fat can be shown to be substituted for one another by the living body in exact proportion to the heat produced in their oxidation outside the body to the same end-products as within the body, the total production of heat per unit of body-weight during rest being nearly the same as with a sufficient diet. This was a very remarkable conclusion, and is one of the foundations of human dietetics. The calorie or heat value of foodstuffs is now a very familiar conception; but perhaps few people are aware that the significance of this conception depends on the fact that in the living body the consumption of food material is normally regulated according to its energy value. Not only do the oxidation processes in the bodies of higher animals occur within living cells, but the regulation of these processes by the cells is an amazingly exact one.
Still another example of the same movement concerns the physiology of glandular secretion generally, including secretion of urine by the kidneys. As already mentioned, the idea that the kidneys and other glands act mechanically as filters of some kind was prevalent up to well on in the nineteenth century; but this theory in its original crude form was swept away by the microscopical investigations of Johannes Müller, who showed that the fine vessels or pores assumed by the theory do not in fact exist. The chemical analyses of Liebig and others showed, moreover, that as the concentration of urea and other substances in the urine, or of various other substances in other secretions, may be far higher than in the blood, no mere filtration theory of glandular secretion is possible.
In the course of the mechanistic movement of the middle of last century a modified filtration theory of urinary secretion was put forward by Ludwig. The connexion of the glomeruli with the tubules, and the general arrangement of the former, had been discovered by Bowman. Ludwig's theory was that the urine is separated in the glomeruli by a process of filtration through a membrane impermeable to the albumins of the blood, just as vegetable parchment is impermeable to them. According to the theory the dilute liquid thus separated is concentrated, as it passes onwards through the tubules, by a process of osmosis, the water being absorbed back into the blood until the urine takes on its characteristic concentration. In support of the filtration part of this theory he brought considerable experimental evidence.
The investigation of secretion was taken up later by Heidenham. He pointed out that urine could not be concentrated by osmosis, since as a general rule urine placed in contact with blood through a membrane permeable only to water would gain water by osmosis from the blood. This part of Ludwig's theory was clearly impossible, and it was only the rudimentary knowledge of physical chemistry which existed when he wrote that made such a theory ever seem possible. Bowman had, on purely anatomical grounds, suggested that the liquid of the urine is separated off in the glomeruli, while dissolved solid constituents are added as this dilute liquid passes down the tubules. Heidenham supported this general conception by various experiments and arguments, and insisted particularly on the necessity of the secreting cells being alive and supplied normally with oxygen. It is evident that the composition of the liquid flowing down the tubules may be modified either by the addition of substances separated from the blood by the cells forming the tubules, or else by the withdrawal from the liquid of water and other dissolved constituents which are returned to the blood from the liquid by the cells. Since Heidenham's time considerable evidence has accumulated in favour of the latter view; but on either view the normal functioning of the kidneys depends on the living activity of the tubule cells. Heidenham's conclusions were sometimes regarded as a revival of vitalism, but they were only part of the general movement seen also in the conclusions of other physiologists whose work has just been referred to.
Closely connected with this movement towards centring physiological activity in living substance were the investigations of Pasteur and his school on the processes of fermentation, putrefaction, and infection. Pasteur made it clear that all these processes are centred in living organisms, and that just as the cells in higher organisms are derived directly from pre-existing cells, so the organisms of fermentation and infection are derived from pre-existing organisms.
For the mechanistic theory of life the essential mechanisms thus came to be located within living protoplasm. This mechanism could not be seen with the microscope, but its existence had to be assumed since no other possibility than its existence seemed open to the mechanistic theory. We cannot otherwise make even a start towards a physico-chemical theory of why each living cell behaves as it does. How the mechanism reproduces itself in successive generations of cells, or how its stability is maintained, had to be left an open question.
It is very generally supposed that on the publication in 1859 of Darwin's Origin of Species a mechanistic explanation of the origin of structure had been discovered. Darwin showed that the characters of a species are not fixed, but are subject to alteration. He also pointed out conditions on which the survival of any species or variation in it must depend, so that any variation which gives a species more chance of surviving must be perpetuated, with the extinction of competing organisms. Thus by a process of natural selection which is still in constant operation, species have become what they are. But the theory depends on the assumption of hereditary transmission from generation to generation of the new characters which have been evolved, together with all the other structural characters. We can imagine that in the course of long ages great variety of structure has been evolved in living organisms; but this throws no light whatever on the fundamental physiological question as to any physico-chemical process by which this structure is constantly reproduced and maintained.
The fact of evolution takes us not a step nearer to the answer to this question, however strongly we may be convinced that evolution is a “natural” process. Darwin made a final end of the science or theology which treated creation as an act by which a vast amount of structural machinery was at one stroke brought into being and then left to act. But he did not put in its place any mechanistic theory of how an organism not only maintains, but transmits from generation to generation its specific structure.
The real assumption behind the mechanistic physiology of last century was that the whole of the visible world of Nature can be interpreted as a physico-chemical system in the sense of Newton's mechanical interpretation of the inorganic world. If the phenomena of life are natural phenomena, they must on this assumption be mechanical phenomena. But the question for a biologist is whether the assumption will fit the data of his observations. In the discussion so far we have referred to a considerable mass of data which can be interpreted very successfully on the mechanistic theory, provided that the mechanisms concerned can be actually discovered or imagined, and provided also that explanation is not required as to the maintenance and reproduction of these mechanisms.
These provisions are essential; but they were simply ignored in the prevalent mechanistic physiology of the latter half of last century, and were not realized until physiology had reached a further stage of development, which will be discussed in the next lecture.
Liebig, Die organische Chemie in ihrer Anwendung auf Physiologie und Pathologie, 1842.