The rather lengthy discussion of the last chapter was necessary in order to show just how far the principles of energetics established by the physicists applied to the organism. We have seen that the first law of thermodynamics does so apply with all its exclusiveness. The more carefully a physiological experiment is made; the more closely do its results correspond with those which theory demands. It is true that relatively few experimental investigations can be controlled in this way, but in those that can be checked by calculation (as, for instance, in the well-known calorimetric experiments) everything tends to show that precisely the same quantities of matter and energy enter the body of an organism in the form of food-stuff, that leave it as radiated and conducted heat, as work done, and as the potential chemical energy of the excretions. Even when we are unable (as in most investigations) to apply the test of correspondence with theory, we have the conviction that the law of conservation holds with all its strictness.

Then, whenever it was possible to apply the methods of chemistry and physics to the study of the organism, it was seen that the processes at work were chemical and physical. The substance of the living body was seen to consist of a large (though limited) number of chemical compounds, differing mainly from those which exist in inorganic nature in their greater complexity. It was also seen that physico-chemical reactions occurred in living substance analogous with, or quite similar to, those which could be studied in non-living substance. The conclusion, then, was irresistible that the life of the organism was merely a phase in the evolution of matter and energy, and differed in no essential respect from the physico-chemical activities that could be observed in the non-living world.

These conclusions were stated so well by Huxley in his famous lecture on “The physical basis of life,” over forty years ago, that all subsequent utterances have been merely reiterations of this thesis in a less perfect form. The existence of the matter of life, Huxley said, depended on the pre-existence of certain chemical compounds—carbonic acid, water, and ammonia. Withdraw any one of them from the world and vital phenomena come to an end. They are the antecedents of vegetable protoplasm, just as the latter is the antecedent of animal protoplasm. They are all lifeless substances, but when brought together under certain conditions they give rise to the complex body called protoplasm; and this protoplasm exhibits the phenomena of life. There is no apparent break in the series of increasingly complex compounds between water, carbon dioxide, and ammonia, on the one hand, and protoplasm on the other. We decide to call different kinds of matter carbon, oxygen, hydrogen, and nitrogen and to speak of their activities as their physico-chemical properties. Why, then, should we speak otherwise of the activities of the substance protoplasm?

“When hydrogen and oxygen are mixed in certain proportions and an electric spark is passed through them they disappear, and a quantity of water, equal in weight to the sum of their weights, appears in their place. There is not the slightest parity between the passive and active powers of the water and those of the oxygen and hydrogen that have given rise to it.... We call these and many other phenomena, the properties of water, and we do not hesitate to believe that in some way they result from the properties of the component elements of the water. We do not assume that a something called “aquosity” entered into and took possession of the oxide of hydrogen as soon as it was formed and guided the aqueous particles to their places in the facets of the crystal, or among the leaflets of the hoar frost.”

“Is the case in any way changed when carbonic acid, water, and ammonia disappear, and in their place, under the influence of pre-existing protoplasm, an equivalent weight of the matter of life makes its appearance?”

“It is true that there is no sort of parity between the properties of the components and the properties of the resultant. But neither was there in the case of water. It is also true that the influence of pre-existing protoplasm is something quite unintelligible. But does anyone quite understand the modus operandi of an electric spark which traverses a mixture of oxygen and hydrogen? What justification is there, then, for the assumption of the existence in the living matter of a something which has no representative or correlative in the non-living matter which gave rise to it?”

All the investigations of over forty years leave nothing to be added to this statement of what, in Huxley’s days, was called materialistic biology. It was a very unpopular statement to make then, but it has become rather fashionable now. Let the reader compare it with all that has been spoken and written since 1869, even with the utterances of the British Association of the year 1912, and he will find that it expresses the point of view of mechanistic biology far better than all the subsequent restatements. The only difference he will find is that the latter have become (as William James has said about academic philosophies), rather shop-soiled. They have been reached down and shown so often to the enquiring public, that each display has taken away something of their freshness.

Now Huxley’s example leads up so well to the consideration of the differences between the chemical activities of the organism and those of inorganic matter that we may consider it in some detail. What, then, is the difference between the explosion of a mixture of oxygen and hydrogen, and the photo-synthesis of starch by the green plant?

In the case of the synthesis of water we have an example of an exothermic chemical reaction. We are to think of the mixture of oxygen and hydrogen as existing in a condition of “false equilibrium.” It may be compared with a weight resting on an inclined plane.

Suppose that the plane is a sheet of smoothly polished glass, and that the weight is a smooth block of glass. By canting the plane more and more an angle will be found at which the slightest push starts the weight sliding down. Now in the case of the explosive mixture of oxygen and hydrogen we have a chemical analogue. Either the gases do not combine at all at the ordinary temperature or they combine “infinitely slowly.” But the slightest impulse, an electric spark requiring an almost infinitesimally small quantity of energy, starts the combination of the gases, and this continues until all is changed into water vapour. In this reaction a large quantity of energy is liberated in the form of heat. This heat becomes transformed into the kinetic energy of the water particles which condense from the steam formed in the explosion, and these particles assume the temperature of their surroundings. The energy which was potential in the explosive mixture, and which was capable of doing work, still exists as the kinetic energy of the water formed, but it has become unavailable for any natural process of work.

We have seen what is the general character of the reaction series in the course of which carbon dioxide and water become starch; and then this, becoming first soluble, and becoming associated with the ammonia or nitrate taken into the plant, becomes protoplasm. It is a reaction which differs from that just described, in that available energy becomes absorbed and accumulated, and retains the power of doing work. It is not a reaction which can be initiated by an infinitesimal stimulus, but one in which just as much energy is required in order that it may happen as is represented in the energy which becomes potential in the living substance generated. The first reaction is one which may take place by itself;17 the other is one which requires a compensatory energy-transformation in order that it may happen. In the first reaction energy is dissipated; in the second one it is accumulated.

We are thus led to the consideration of the second principle of energetics and its limitations, but before entering upon this discussion we must consider the nature of the activities of the organism.

By the term “metabolism” we understand the totality of the physico-chemical changes which occur in the living substance of the organism. In physiological writings we usually find that two categories of metabolic changes are described: (1) anabolic processes, in the course of which simple chemical compounds possessing relatively little energy are built up into much more complex substances, containing a relatively large quantity of available energy, and therefore capable of doing work. The transformations constituting an anabolic change must be accompanied by corresponding compensatory energy-transformations, to account for the energy which becomes potential in the substances formed. The formation of starch from carbon dioxide and water, by the green plant, is such an anabolic change, and the compensatory energy-transformation is the absorption of radiation from the ether by the cells of the plant. A further anabolic change in the plant organism is the formation of amido-substances from the ammonia or nitrate absorbed from the soil, and from the soluble carbohydrates formed from the starch manufactured in the green cells.

The typical activities of the chlorophyll-containing organism are of this nature; they are anabolic. The organism may be a green land-plant; a marine green, red, or brown alga; a yellow-green diatom, a yellow, green, red, or brown peridinian or other holophytic protozoan; an ascidian, mollusc, echinoderm, polyzoan, worm, or coral containing “symbiotic algÆ” (that is the chlorophyll-containing cells of some plant organism which have become associated with the animal and incorporated in its tissues). In all these cases the presence of this chlorophyllian substance confers on the organism the power of effecting the compensatory energy-transformation, by the aid of which carbon dioxide and water are built up into starch. What this transformation is, and what are the steps by which the carbon dioxide and water become carbohydrate we do not exactly know. Solar radiation impinging upon an inorganic substance is partly reflected and partly absorbed. The absorbed fraction may become transformed in such a way as to render the substance phosphorescent, or it may transform into chemical energy, as when light impinges on a photographic plate, but as a general rule it is transformed into heat. In the green plant, however, the transformation of radiation into heat does not occur—at least the heating is very small—and it passes directly or indirectly into the potential chemical energy of the starch which is synthesised. We must regard this power of absorbing radiation and utilising it in compensatory transformations as a general character of protoplasm. It is true that it is now specialised in the cells containing the chlorophyll bodies, but there are indications that it may be present in the tissues of the animal devoid of chlorophyll.

Other anabolic transformations occur in the animal. The food-stuffs which are absorbed from the intestine are substances which have undergone dissociations, the nature of which is such as to render them capable of absorption and of reconstruction. These anabolic changes in the higher animal are exceptional, and their usefulness lies in the fact that by their means substances become capable of being transported by the tissue fluids of the body.

(2) Katabolic changes in the animal body correspond in their frequency of occurrence to the anabolic changes of the plant organism. In them complex chemical substances undergo transformation into relatively simple substances, and the contained energy at the same time undergoes a parallel transformation, passing into the form of heat and mechanical energy, while a fraction becomes dissipated. Food-stuffs taken into the alimentary canal break down in this way, but to a very limited extent. Proteids undergo dissociation or decomposition into amido-substances, while fats are dissociated into fatty acids and glycerine. Doubtless energy is dissipated in these processes, serving no other purpose but to heat the contents of the alimentary canal, but this energy-transformation has not been worked out very completely and it is a question whether, given a healthy animal and perfect food-stuffs, any energy would necessarily be lost during the digestive processes. The reactions involved in the latter do not belong to the category of chemical changes proceeding from the complex to the simple, with a liberation of energy; but appear to involve rather a rearrangement of the constituents of a complex molecule, a process in which the contained energy need not undergo change in quantity. These processes involve the action of enzymes.

Enzymes play a great part in modern physiological theory and we must consider them in detail. Let us attach a concrete meaning to the general notion of enzyme-activity by considering the phenomena known as catalysis. The metal platinum can be brought into a very fine stage of division when it is known as platinum black. In this condition it brings about reactions in chemical mixtures or substances which would not otherwise occur: a mixture of oxygen and hydrogen explodes when brought in contact with platinum black, and a mixture of coal gas and air inflames, a reaction which is made use of in the little gas-lighting apparatus which most people have seen. If, again, a powerful electric current be passed between platinum wires which are a little distance apart, and are immersed in water, the metal becomes torn away from the points of the wire in the form of an impalpable powder, colloidal platinum. The liquid containing this colloid then has the power of setting up chemical changes in other substances, changes which would not otherwise occur, or, at least, would occur very slowly.

In general such catalysts, platinum black or colloidal platinum for instance, have the following characters: (1) a small quantity is sufficient to cause change in a large (theoretically an infinite) quantity of the substance acted upon; (2) the nature and quantity of the catalyst remain at the end the same, as at the beginning of the reaction; (3) a catalyst does not start a reaction in any other substance or substances, it can only influence the rate at which this reaction may occur: apparently it does, in some cases, start a reaction, but in such cases we suppose that the latter proceeds so slowly as to be imperceptible; (4) the final state of the reaction is not affected by the catalyst; it depends only on the nature of the interacting substance or substances; (5) the final state is not affected either by the nature or quantity of the catalyst: it is the same if we employ different catalysts, or a large or small quantity of the same catalyst. Finally, it appears that the phenomena of catalysis are universal: “There is probably no kind of chemical reaction,” says Ostwald, “which cannot be influenced catalytically, and there is no substance, element, or compound which cannot act as a catalyser.”18

Enzymes, then, are agents which are produced by the organism, and which act by influencing (accelerating or retarding) chemical reactions. An enzyme, as such, need not exist in a tissue; it is there as a zymogen, a substance which may become an enzyme when required. An enzyme need not be active: it may be necessary that it should be “activated” by a kinase, another substance produced at the same time. Associated with many enzymes are anti-enzymes, substances which undo what their corresponding enzymes have done. Finally some, perhaps most, enzymes are reversible, that is, if they produce a change in a certain substance they can also produce the opposite kind of change: the meaning of this will become clearer a little later on. We have spoken of enzymes as “agents” or “substances,” but it is not at all certain that they are definite chemical compounds. In the preparation of an enzyme what the bio-chemist obtains is a liquid, a glycerine or other extract which possesses catalytic properties. An actual catalytic substance, like platinum black, cannot be obtained from this liquid. A white powder may be obtained, but this usually proves to be proteid in composition; it is not the actual enzyme itself but is the impurity associated with the latter. Now the very great number of enzymes “isolated” by the physiologists has rather destroyed the original simplicity of the idea of enzyme activity and suggests a parallel statement to that made by Ostwald about catalysts: any tissue substance may influence the reactions that may possibly occur in other tissue substances. But while pure chemistry has to deal with definitely known chemical compounds in the phenomena of catalysis, this cannot be said to be the case with physiology in dealing with enzymes. Reasoning by analogy, we may say that it is probable that enzymes are definite proteids, or chemical substances allied to these, but this has not been clearly demonstrated, and it is possible that the phenomena of enzyme activity may belong to some other category of energy-transformations.

However this may be, the conception is a useful one in describing the reactions of the organism, and it may be illustrated by considering the digestion and absorption of fat in the mammalian intestine, a process which appears to be better known than that of proteid digestion. A neutral fat consists of an acid radicle, oleic, palmitic or stearic acids, for instance, united with glycerine. The action of the pancreatic or intestinal enzymes is to dissociate this fatty salt. Let us write the formula of the latter as G F, G being the glycerine base, and F the fatty acid; then

G F G+F

which means that the enzyme can cause the neutral fat to dissociate into glycerine and fatty acid. This action will go on until a state of equilibrium is attained, in which there is a certain quantity of each of the radicles, and a certain quantity of unchanged neutral fat, the ratio of all these to each other depending on various things. When this state of equilibrium is attained the enzyme does indeed go on splitting up more neutral fat, but it is a reversible enzyme, and it also causes the glycerine and fatty acid already split up to recombine, forming neutral fat. A condition is, therefore, reached in which the composition of the mixture remains constant.

Now there is dissociated fat in the intestine after a meal, but there is only neutral fat in the wall of the intestine. The fat itself cannot pass through the cells forming the intestinal wall, but the glycerine and fatty acid into which it is dissociated can so pass, since they are soluble in the liquids of the intestine. We suppose that the cells of the wall of the intestine also contain the fat-splitting ferment; this ferment in the cells acts on the glycerine and fatty acid immediately they enter and recombines these radicles again into neutral fat, the above equation now reading from right to left. But after a time this reaction in the cells will also begin to reverse, for the enzyme will begin to split up the synthesised neutral fat when the state of chemical equilibrium in the new conditions is attained. Fatty acid and glycerine will then diffuse out from the cells into the adjacent lymph stream or blood stream—perhaps neutral fat will also pass from the cells into these liquids, we are not sure. At all events the lymph and blood after a meal containing much fat are crowded with minute fat globules. But why are there no fatty acids or glycerine in the blood, for the latter also contains lipase (the fat-splitting enzyme)? The explanation is, apparently, that either an anti-enzyme is produced, or that the enzyme passes into a zymoid condition. Why also does fat accumulate in the tissues? Here, again, the activity of the enzyme, which from other considerations we may regard as being universally present almost everywhere in the body, must be supposed to be arrested by some means.

The conception of a catalytic agent, such as we can study in pure chemistry, thus carries us a long way in our description of the processes of digestion, absorption, and assimilation. We have applied it to the case of fat-digestion, but very much the same general scheme might also apply to many other processes in the body. Obviously it enables us to describe these processes in terms of physico-chemical reactions, but we cannot fail to see that ultimately we are compelled to assume the existence of reactions which were not included in the original conception—the activation of the enzyme at the proper moment by the kinase, the operation of the anti-enzyme, and the passage of the enzyme into the zymoid. Just why these things happen as they do we do not know, yet the whole problem becomes shifted on to these reactions.

In the same way we apply the purely physical processes of the osmosis and diffusion of liquids to the circulation of substances in the animal body. The nature of these processes will probably be familiar to the reader, nevertheless it may be useful to remind him that by diffusion we understand the passage of a liquid, containing some substance in solution, through a membrane; and by osmosis the passage of a solvent (but not of the substance dissolved in it) through a “semi-permeable membrane.” The molecules of the solvent (water, for instance) pass through the membrane (the wall of a capillary, or lymphatic vessel), but the molecules of the substance (salt, for instance) dissolved in the solvent do not pass. Let us suppose that a strong solution of common salt in water is injected into the blood stream: what happens is that osmosis takes place, the water in the surrounding lymph spaces passing into the blood stream because the concentration of salt there is greater than it is in the lymph. While this is happening, the capillary walls are acting as semi-permeable membranes, allowing the molecules of water to pass through but not the molecules of salt. Very soon, however, the process of osmosis becomes succeeded by one of diffusion, and the salt molecules pass through the capillary wall into the lymph and are excreted.

Undoubtedly the purely physical processes of diffusion and osmosis occur all over the animal body and are the means whereby food-materials, secretory, and excretory substances are transported from blood to lymph, or vice versa, from lymph to cell substance or to glandular cavities, and so on. But it is also the case that in very many processes the activity of the cells themselves plays an important part. It may even be the case that a particular process, after all physical agencies are taken into account, reduces down to this action of the cells. To understand this we must consider the mode of working of some well-known organ, and the best possible example of such an organ, considered as a mechanism, is that of the sub-maxillary salivary gland of the mammal.

What, then, is this mechanism and how does it act? The gland is a compound tubular one, its internal cavity being prolonged into the duct which opens into the mouth. The saliva prepared in the gland issues from this duct. Blood is carried to the gland by twigs of the facial artery, and, after circulating through it, is carried away by factors of the jugular vein. Two nerves supply the gland: one is the chorda tympani, a branch of a cranial nerve, and the other is a sympathetic nerve. Lymph also leaves the gland by a little vessel.

Now suppose we have laid bare all this mechanism in a living animal and make experiments upon it. If we stimulate the chorda tympani there is a copious flow of thin watery saliva, but if we stimulate the sympathetic there is a less copious flow of thick viscid saliva. Why is this? We find on closer analysis that the chorda contains fibres which dilate the small arteries so that there is an increased flow of blood through the gland; but that, on the other hand, the sympathetic contains fibres which constrict the arteries, thus leading to a reduced flow of blood. This accounts for the fact that “chorda-saliva” is abundant and thin, while “sympathetic-saliva” is scarce and thick. It was thought at one time that the chorda contained fibres which stimulated the gland to produce watery saliva, while the sympathetic contained fibres which stimulated it to produce mucid saliva. This, however, is not the case. Both nerves contain the same kind of secretory fibres: their other fibres differ mainly in that they act differently on the arteries.

It might be the case—indeed it was at one time thought that it was the case—that secretion of saliva was simply a matter of blood-flow: an abundant arterial circulation gave rise to abundant saliva, a sparse flow to a sparse saliva. Undoubtedly the secretion depends on blood supply, but not solely. If it did, then the whole process might be conceived to be a very simple mechanical one—filtration or diffusion of the saliva from the blood stream through the thin walls of the blood vessels, and the walls of the tubules into the cavity of the gland. If this were the case, then the liquid in the gland would be the same in composition and concentration as the liquid part of the blood—the plasma. But it is really different in composition and it is not so concentrated. Now osmotic pressure—on the action of which so much is based—cannot help us, for the liquid in the gland is less concentrated than that in the blood vessels, so that water ought to pass from gland to blood instead of from blood into gland. Again, if we tie the duct, so that the saliva cannot escape, secretion still goes on, though the hydrostatic pressure of saliva in the cavity of the gland may be considerably greater than that of the liquid in the blood vessels. Yet again, if we stop the blood flow by tying the artery, secretion of saliva may still go on for a time.

Therefore the only physical agencies we can think of do not explain the secretion. The latter is actually the work of the individual cells, stimulated by the nerves. If the volume of the gland be measured just while it is being stimulated to secrete, it will be found that the organ becomes smaller, yet while it is being stimulated the blood-vessels are being dilated so that the volume of the whole structure ought to become greater. Obviously part of the substance of the gland is being emptied out through its duct as the secretion.

If we examine the cells of the gland in various states we see clearly that granules of some material, different in nature from the substance of the protoplasm itself, are being formed within them. Evidently these granules swell up during secretion and discharge their contents into the ducts. Further changes in the characters of the cell-substance, and in the nucleus, can be observed, and all these indicate that the protoplasm of the cells, as the result of stimulation, elaborates certain substances; that these substances are then washed out, so to speak, into the duct by the withdrawal of water from the cell; and that thereafter the cell absorbs fresh nutritive material from the lymph which exudes from the blood vessels, along with water. The distinctive part of the whole train of processes is, then, this elaboration of material by the cells themselves; while the concomitant changes in the calibre of the blood vessels and in the flow of blood and lymph are subsidiary ones. In the process of secretion of saliva energy is absorbed from the chemical substances of the blood to bring about the passage of water from a region of high to a region of low osmotic pressure; oxygen and nitrogen, with other elements of course, are withdrawn from the arterial blood stream for the purpose of the secretion, and carbon dioxide and other substances are given off to the venous blood and lymph.

The problem thus is pushed back from the mechanical events occurring in the nervous and circulatory processes, to the physico-chemical ones occurring in the cells of the gland tubules; and it thus becomes much more obscure. It is true that we can formulate a hypothesis which describes, in a kind of way, these intra-cellular metabolic changes, in terms of physico-chemical reactions, and, without doubt, reactions of this kind must occur within the cell. But if we could test any such hypothesis as easily as the mechanical ones suggested, should we find it any more self-sufficient?19

Irritability and contractility are general properties of the organism. These properties are illustrated by the irritability of an Amoeba or Paramoecium to stimuli of many kinds; by the movements of the pseudopodia of the former animal, or of the cilia of the latter; by the nervous irritability of the higher animal, and the contraction of its muscles when they are stimulated. They are among the fundamental properties or functions of living protoplasm, and their study is of paramount interest, and carries us to the very centre of the problem of the activities of the organism. Naturally physiologists have never ceased to attempt to describe irritability and contractility in terms of physics, but though we may be quite certain that the things that do occur in these phenomena are controlled physico-chemical reactions, it must be remembered that what we positively know about their precise nature is exceedingly little.

What is the nature of a nervous impulse? When a receptor organ is stimulated, as, for instance, when light impinges on the cone cells of the retina, or when the nerve-endings in a “heat-spot” in the skin are warmed, or when the wires conveying an electric current are laid on a naked nerve, an impulse is set up in the nerve proceeding from the place stimulated, and we must suppose that approximately the same amount of energy moves along the nerve as was communicated to the receptor or the nerve itself by a stimulus of minimal strength. How does it so move? Several facts of capital importance result from the experimental work. (1) The impulse travels with a velocity variable within certain limits, say from 8 to 30 metres per second; (2) it travels faster if the temperature is raised (up to a certain limit); (3) it is difficult to demonstrate that the passage of this impulse is accompanied by definite chemical changes in the nerve substance: it is stated that carbon dioxide is produced, but this is not certainly proved; (4) an electric current is produced in the nerve as the result of stimulation; (5) no heat is produced, or at least the rise of temperature, if it occurs, is less than 0.0002°C.

Thus it is quite certain that physical changes accompany the propagation of the nerve-impulse, for the latter has a certain velocity, which depends on the temperature, and an electric change also occurs in the substance of the nerve. Is this electric change the actual nerve impulse? It is hardly likely, since the velocity of the impulse is very much less than that of the propagation of an electric change through a conductor; besides, the passage of the impulse is not accompanied by a measurable heat evolution, although the flow of electricity along a poor conductor must generate heat and dissipate energy. Is it a chemical change? Then we should be able to observe metabolism in the nerve substance—that is if the energy-change is a thermodynamic one—while it is not at all certain that metabolic changes do occur. Nevertheless it seems probable that a physico-chemical change is actually propagated when we consider the chemical specialisation of the substance of the axis-cylinder of the nerve. Now the velocity of propagation of the nervous impulse is of the same order of magnitude as that of an explosive change in chemical substances (using the term “explosion” to connote chemical disintegrations rather than combustions). If we imagine a long rod of dynamite, or picric acid, or a long strand of loosely-packed gun-cotton to be exploded by percussion at one end, then a transmission of the chemical disintegration of any of these substances will pass along the rod, etc., with a velocity which will certainly vary with the physical condition of the material. It would be a high velocity in a rod of dynamite, or fused picric acid, but a lower velocity in a loosely aggregated strand of gun-cotton, or a trail of picric acid powder. Is this what happens in the nerve when an impulse travels along it? Obviously not, since the substance of the nerve is not altered appreciably, while that of the explosive substance passes into other chemical phases. We might imagine, then, such a change in the nerve fibrils as that of a reversible transformation of some chemical constituent:—

Let us imagine the substance of the fibril to be composed of, or at least to contain, the substances a+b which dissociate reversibly into the substances c+d. At any moment, and in any particular physical state, as much of a and b pass into c and d as c and d pass into a and b. There will be equilibrium. But now let a stimulus alter the physical conditions: prior to the stimulus the phase was a_m+b_n = c_p+d_r—the suffixes m, n, p, r, denoting the concentrations of a, b, c, and d—but after the stimulus the phase may be a_m¹+b_n¹ = c_p¹+d_r¹. Now the element of the nerve substance (1) forms a system with the element (2). The condition in (2) is a_m+b_n = c_p+d_r, and that of (1) a_m¹+b_n¹ = c_p¹+d_r¹, but these two together now fall into a new state of equilibrium and this is transmitted along the whole nerve-fibril with a velocity which belongs to the order of magnitude of that of chemical changes. If the stimulus remains constant (a constant electric current for instance), the new condition of equilibrium will be established throughout the whole length of the fibril and the nervous impulse will be a momentary one (as it is in this case). But if the stimulus is an intermittent one (an interrupted electric current, light-vibration, sound-vibrations), then in the intervals the former condition of equilibrium will become re-established and the nervous impulse will be intermittent (as it is). There would be no work done on the whole in the changes, except that done by the transmission of the changed state of equilibrium to the substance of the effector organ in which the nerve-fibril terminates—the substance of a muscle fibre, or the cell of a secretory gland, for instances. There would, probably, be a certain dissipation of energy as in the case of the propagation of an electric impulse through a poor conductor, but all our knowledge of the chemistry of the nerve fibre points to this amount of dissipation as tending to vanish.

Something analogous to this may be expected to take place in a muscle fibre when it contracts; except that, of course, energy is transformed in this case. What precisely does happen we do not know and at the present time no physico-chemical hypothesis of the nature of muscular contraction exactly describes all that can be observed to take place. Certain positive results have, of course, been obtained by chemical and physical investigation of the contracting muscle: carbon dioxide is given off to the lymph and blood stream, and the amount of this is increased when an increased amount of work is done by the muscle; heat is produced and this too increases with the work performed; glycogen is used up, and lactic acid is produced; finally oxygen is required, and more oxygen is required by an actively contracting muscle than by a quiescent one. Now the obvious hypothesis correlating all these facts is that the muscle substance is oxidised, and that the heat so produced is transformed into mechanical energy. “We must assume,” says a recent book on physiology, “that there is some mechanism in the muscle by means of which the energy liberated during the mechanical change is utilised in causing movement, somewhat in the same way as the heat energy developed in a gas-engine is converted by a mechanism into mechanical movement.”

Now, must we assume anything of the kind? To begin with, life goes on, and mechanical energy is produced in many organisms living in a medium which contains no oxygen. Anaerobic organisms are fairly well known, and we cannot suppose that in them energy is generated by the combustion of tissue substance in the inspired oxygen. A muscle removed from a cold-blooded animal will continue to contract in an atmosphere containing no oxygen, and it will continue to produce carbon dioxide. It is true that the contractions soon cease, even after continued stimulation under conditions excluding the fatigue of the muscle, but do the contractions cease because the oxygen supply is cut off, or because the muscle dies in these conditions? We know that some complex chemical substance is disintegrated during contraction and that mechanical energy and heat are produced and that carbon dioxide is also produced. We know that the carbon contained in the latter gas corresponds roughly with the carbon contained in the muscle substance which undergoes disintegration, but does all this justify us in saying that this substance is oxidised in order that its potential chemical energy may be transformed into mechanical energy? Obviously not, since we might equally well suppose that the complex metabolic substance of the muscle splits down into simpler substances and that in this transformation energy is generated. Suppose that these simpler substances are poisonous and that they must be removed as rapidly as formed. The rÔle of the oxygen may be to oxidise them, thus transforming them into carbon dioxide, an innocuous substance which can be carried away quickly in the blood stream. This line of thought, according to which the rÔle of oxygen is an anti-poisonous one, is held at the present day by some physiologists, and many considerations appear to support it; the existence of “oxidases,” for instance, enzymes which produce oxidations which would not otherwise occur in their absence. Such enzymes exist in very many tissues, and they may, apparently, be present in an inactive form, requiring the agency of a “kinase” before they are able to act.

The usual view among physiologists is that the muscle fibre is a thermodynamic apparatus transforming the heat generated during metabolism into mechanical energy. How is this transformation effected? It cannot be said that we have any one hypothesis more convincing than another. It has been suggested that alterations of surface tension play a part, or that the heat produced by oxidation causes the fibre to imbibe water and shorten. Engelmann has devised an artificial muscle consisting of a catgut string and an electrical current passing through a coil of wire, and by means of this he has reproduced the phenomena of simple contraction and tetanus. But it remains for future investigation to verify any one of these hypotheses.

When Huxley published his Physical Basis of Life, probably few physiologists had any doubt that protoplasm was a definite chemical substance, differing from other organic substances only by its much greater complexity. But in 1880 Reinke and Rodewald published the results of an analysis of the substance of a plant protoplasm and these appear to have demonstrated that the substance was really a mixture of a number of true chemical compounds and was not a single definite one. Now all of these substances might exist apart from protoplasm, and in the lifeless form, and a simple mixture of them could hardly bring forth vital reactions. These results were followed by the morphological study of the cell—the discovery of the architecture of the nucleus, and so on, and so opinion began to turn to the hypothesis that the vital manifestations of protoplasm were the result of its structure. Microscopical examination of the cell appeared to disclose a definite arrangement, the “foam” or “froth” of Butschli, for instance. But, again, it was easily shown that the foam, or alveolar structure of protoplasm was merely the expression of physical differences in the substances composing the cell-stuff—they reduced to phenomena of surface tension and the like. Artificial protoplasm and artificial AmoebÆ were made—at least mixtures of olive oil and various other substances were made which simulated many of the phenomena of protoplasm in much the same way as crystalline products may be made which simulate the growth of a plant stem with its branches. For instance, one has only to shake up a little soapy water in a flask to see what resembles surprisingly the arrangement of certain kinds of connective tissues in the organism. Obviously these artificial phenomena have nothing to do with living substance.

Yet if we grind up a living muscle with some sand in a mortar we do destroy something. The muscle could be made to contract, but after disintegration this power is lost. We have certainly destroyed a structure, or mechanism, of some kind. But, again, the paste of muscle substance and sand still possesses some kind of vital activity, for with certain precautions it can be made to exhibit many of the phenomena of enzyme activity displayed by the intact muscle fibres, or even the entire organism. Mechanical disintegration, therefore, abolishes some of the activities of the organism, but not all of them. If, however, we heat the muscle paste above a certain temperature, the residue of vital phenomena exhibited by it are irreversibly removed, so that heating destroys the mechanism. This we can hardly imagine to be the case (within ordinary limits of temperature at least) with a physical mechanism, but again a mechanism which is partly chemical might be so destroyed. We see, then, that protoplasm possesses a mechanical structure, but that all of its vital activities do not necessarily depend on this structure. The full manifestation of these activities depends on the protoplasmic substance possessing a certain volume or mass, and also on a certain chemical structure.

If living protoplasm has a structure, and is not simply a mixture of chemical compounds, what is it then? Two or three physico-chemical concepts are at the present time very much in evidence in this connection. When the substances known as colloids were fully investigated by the chemists, much attention was paid to them by the physiologists, so that life was called “the chemistry of the colloids,” just as after the investigation of the enzymes it was called the “chemistry of the enzymes,” and when the discovery of the relative abundance of phosphorus in cell-nuclei and in the brain was discovered, it was called the “chemistry of phosphorus.” Colloids (e.g. glue) are substances that do not readily diffuse through certain membranes, in opposition to crystalloids (e.g. solution of common salt) which do readily so diffuse. They form solutions which easily gelatinise reversibly, that is, can become liquid again (glue); or coagulate irreversibly, that is, cannot become liquid again (albumen); which have no definite saturation point; which have a low osmotic pressure (and derived properties), etc.; and the molecules of which are compound ones consisting of combinations of the molecules of the substance with the molecules of the solvent, or with each other, that is, they are molecular aggregates.

Colloids pass insensibly into crystalloids on the one hand and into coarse suspensions (water shaken up with fine mud, for instance) on the other. We may replace the concept of a colloid by those of “suspensoids” and “emulsoids.” A suspensoid is a liquid containing particles in a fine state of division—if the division is that into the separate molecules we have a solution, if into large aggregates of molecules we have a suspension. If the substance in the liquid is itself liquid, the whole is called an emulsoid. On the one hand this approaches to a mixture of oil in soap and water—an emulsion—and on the other hand to such a mixture as chloroform shaken up with water, when the drops of chloroform readily join together so that two layers of liquid (chloroform and water) form. What we see, then, in protoplasm is a viscid substance possessing a structure of some kind, and containing specialised protoplasmic bodies in its mass (nuclei, nucleoli, granules of various kinds, chlorophyll, and other plastids, etc.). It may contain or exhibit suspensoid or emulsoid parts or substances, or it may contain truly crystalloid solutions. These phases of its constituents are not fixed, but pass into each other during its activity. Nothing that we know about it justifies us in speaking about a “living chemical substance.” On analysis we find that it is a mixture of true chemical substances rather than a substance. It is no use saying that in order to analyse it we must kill it, for what we can observe in it without destroying its structure or activities indicates that it is chemically heterogeneous.

This is not a textbook of general physiology, and the examples of physico-chemical reactions in the organism which we have selected have been quoted in order to show to what extent the chemical and physical methods applied by the physiologists have succeeded in resolving the activities of the organism. The question for our consideration is this: do these results of physico-chemical analysis fully describe organic functioning? Dogmatic mechanism says “yes” without equivocation.

Now it is clear, from even the few typical examples that we have quoted, that physiological analysis shows, indeed, a resolution of the activities of the organism into chemical and physical reactions. How could it do otherwise? How could chemical and physical methods of investigation yield anything else than chemical and physical results? The fact that these methods can be applied to the study of the organism with consistent results shows that their application is valid; that we are justified in seeing physico-chemical activities in life. But are these results all that we have reason to expect?

We turn now to Bergson’s fertile comparison of the physiological analysis of the organism with the action of a cinematograph. If we take a series of photographic snapshots of, e.g., a trotting horse and then superpose these pictures upon each other, we produce all the semblance of the co-ordinated motions of the limbs of the animal. Yet all that is contained in the simulated motion is immobility. From a succession of static conditions we appear to produce a flux. Yet if we could contract our duration of, e.g., a week, into that corresponding to five minutes—if we could speed up our perceptual activity—should we not see the cinematographic pictures as they really are—a series of immovable postures and nothing more: truly an illusion? If, again, we reverse the direction of motion of the film, we integrate our snapshots into something which is absolutely different from the reality which they at first represented; and by such devices the illusions and paradoxical effects of the picture-house farces are made possible. Well, then, in the physiological analysis of the activity of the organism do we not do something very analogous to this? The complexity of even the simplest function of the animal is such that we can only attend to one or two aspects of it at once, arbitrarily neglecting all the rest. We find that the hydrostatic pressure of blood, and lymph, and secretion, the osmotic pressure, the diffusibility, vaso-motor actions, and other things must be investigated when considering the question of how the submaxillary gland secretes saliva. One, or as many as possible, of these reactions are investigated at one time, and then the results are pieced together—integrated—in order to reproduce the full activity of the whole indivisible process. But in doing this do we not introduce something new—a direction or order of happening—into the elements of the dissociated activity of the organism? Each elemental process must occur at just the right time.

What right have we to say that the activity of the organism is made up of physico-chemical elements? Just as much as we have in saying that a curve is made up of infinitesimal straight lines. Let us adopt Bergson’s illustration, with a non-essential modification.

The curve 1–8 is a line which we draw freehand with a single indivisible motion of the hand and arm and eye. It is something unique and individualised, in that no other curve ever drawn, in a similar manner, exactly resembles it. Let us investigate it mathematically. We can select very small portions of it—elements we may call them—and each of these elements, if it is small enough does not differ sensibly from a straight line. Let us produce each of these straight lines in both directions, it is then a tangent to the curve, and it does actually coincide with the curve at one mathematical point—the points 1–8 in the figure. The tangent then has something in common with the curve, but would a series of infinitesimally small tangents reproduce the curve? Obviously not, for the equations of the tangents would have the form ax+b, while that of the curve itself would be quite different, containing x as powers of x, or as transcendental functions of x. In this investigation what we succeed in obtaining are the derivatives of the curve, and to reproduce the latter from its elements we have to integrate the derivatives; that is, another operation differing in kind from our analytical one must be performed. Now in this illustration we have doubtless something more than an analogy with our physico-chemical analysis of life. The activities of the organism do reduce to bio-chemical ones (the elemental straight lines on the curve), and each of these reactions has something in common with life (it is tangent to life, touching it at one point). But if we attempt to reconstitute life from its physico-chemical derivatives we must integrate the latter, and in doing so we over-pass the bounds of physics, just as integrating a mathematical function we necessarily introduce the concept of the “infinitely small.”

The physico-chemical reactions into which we dissociate any vital function of the organism have, then, each of them, something in common with the vital function. But their mere sum is not the function. To reproduce the latter we have to effect a co-ordination and give directions to these reactions. In all physiological investigations we proceed a certain length with perfect success; thus the elements, so to speak, of the function of the secretion of saliva are (1) the blood-pressure, (2) the hydrostatic pressure of the secretion in the lumina of the gland tubules, (3) the diffusibility of the substances dissolved in the blood and lymph through the walls of these vessels, (4) the osmotic pressure of the same substances, and (5) the stimulation of the gland cells by “secretory nerve fires.” Now the investigations carried out—and no part of the physiology of the mammal has been so patiently studied as the salivary gland—fail, so far, completely to describe the function in terms of these elements. In the end we have to refer the secretion to intra-cellular processes, and then we begin to invoke again processes of osmotic pressure, diffusibility, and so on with reference to the formation of the drops of secretion which we can see formed in the gland cells. We are forced to the formulation of a logical hypothesis as to the nature of these intra-cellular processes, and since much that goes on in the cell substance is, so far, beyond physico-chemical investigation, our hypothesis will be as difficult to disprove as to verify.

Let us return now to Huxley’s comparison of the activity of the green plant with the chemical reaction which occurs when an electric spark is passed through a mixture of oxygen and hydrogen. The lecture on the “Physical Basis of Life” was published in 1869; in 1852 William Thomson published his paper “On a Universal Tendency of Nature to Dissipation of Energy,” and a year or two before that Clausius had applied Carnot’s law to the kinetic theory of heat: the second principle of energetics had therefore even then been exactly formulated, but its significance for biological speculation had not been recognised by Huxley, any more than it has generally been recognised by most biologists since 1869. What, then, does the comparison of Huxley show? Clearly that the physical changes which occur in the explosion of a mixture of oxygen and hydrogen trend in a different direction from those which occur in the photo-synthesis of starch by a green plant. Generally speaking, chemical activity, that is, the possibility of occurrence of chemical reactions, is a case of the second law of energetics. Energy passes from a state of high to a state of low potential. A chemical reaction will occur if this change of potential is possible.

In all such changes energy is dissipated. What exactly does this mean? It means that, generally speaking, the potential energy of chemical compounds tends to transform into kinetic energy; while differences in the intensity factor of the kinetic energy of the bodies forming a system tend to become minimal. In a mixture of oxygen and hydrogen there is energy of two kinds, (1) potential energy due to the position of the molecules (O and H molecules are separated); and (2) kinetic energy of the molecules (which are moving about in the masses of gas). After the explosion the potential energy acquired in the separation of the molecules of O and H has disappeared (the molecules having combined to form water), but the kinetic energy has greatly increased, since the explosion results in the formation of steam at high temperature. But now this steam radiates off heat to adjacent bodies, or becomes cooled by direct contact with the envelope which contains it. The energy of the explosion is therefore distributed to the adjoining bodies, and the temperature of the latter becomes raised. But these again radiate and conduct heat to other bodies, and in this way the heat generated becomes indefinitely diffused.

The general effect of all physico-chemical changes is therefore the generation of heat, and then this heat tends to distribute itself throughout the whole system of bodies in which the physico-chemical changes occur. The energy passes into the state of kinetic energy, that is, the motion of the molecules of the bodies to which the heat is communicated. This molecular motion is least in solids, greater in liquids, and greatest in gases. If solids, liquids, and gases are in contact, forming complex systems, the kinetic energy of their molecules becomes distributed in definite ways, depending on the constants of the systems. After this redistribution the kinetic energy of these molecules is unavailable for further energy transformations, so that phenomena or change in the system ceases. There is no longer effective physical diversity among the parts of the system.

We find that this conception of dissipation of energy cannot be applied to the organism, at least not with the generality in which it applies to physical systems. Why? Not because the conception is unsound, or because the physico-chemical reactions that occur in material of the organism are of a different order from those that occur in inorganic systems—they are of the same order. The second law of energetics is subject to limitations, and it is because it is applied to organic happenings without regard to these limitations that it does not describe the activities of the organism as well as it describes those of inorganic nature.

What, then, are these limitations? We note in the first place that the laws of thermodynamics apply to bodies of a certain range of size; or at least the possibility of mathematical investigation (on which, of course, all depends) is limited to “differential elements” of mass, energy, and time. We cannot apply mathematical analysis to bodies, or time-intervals of “finite size,” since the methods of the differential and integral calculus would not strictly be applicable. But molecules are so small (1 cubic centimetre of a gas may contain about 5.4×10¹⁹ of them) that even such a minute part of a body, or liquid, or gas as approximates to the infinitesimally small dimensions required by the calculus, contains an enormous number of molecules.

Obviously we cannot investigate the individual molecules. Even if experimental methods could be so applied, such concepts as density, pressure, volume, or temperature would have no meaning. Physics, then, is based on collections of molecules, and the properties of a body are not those of a molecule of the same body. Such concepts as temperature and pressure are statistical ones, and are applied to the mean properties of a large number of molecules.

We can best illustrate this by considering Maxwell’s famous fiction of the “sorting demons.” Let us imagine a mass of gas contained in a vessel the walls of which do not conduct heat. Let there be a partition in this vessel also of non-conducting material, and let there be an aperture in this partition greater in area than a molecule, but smaller than the mean free path of a molecule. Now this mass of gas has a certain temperature which is proportional to the mean velocity of movement of the molecules. The second law says that heat cannot pass from a cold region in a system to a hot region without work being done on the system from outside, nor can an inequality of temperature be produced in a mass of gas or liquid except under a similar condition. But “conceive a being,” says Maxwell, “whose faculties are so sharpened that he can follow every molecule in its course; such a being, whose attributes are still as essentially finite as our own, would be able to do what is at present impossible to us.”20 For the temperature of the gas depends on the velocities of the molecules, and in any part of the gas these velocities are very different. Suppose that the demon saw a molecule approach which was moving at a much greater velocity than the mean: he would then open the door in the aperture and let it pass through from - to +. On the other hand, should a molecule moving at a velocity much less than the mean approach he would let it pass from + to -. In this way he would sort out molecules of high from those of low velocity. But the collisions between the molecules in either division of the vessel would continually produce diversity of individual velocity, and in this way the difference of temperature between + and - would continually be increased. Heat would thus flow from a region of low to a region of high temperature without an equivalent amount of work being expended.

Now we must not introduce demonology into science, so, lest this fiction of Maxwell’s should savour of mysticism, or something equally repugnant, we shall state the idea involved in it in quite unexceptionable terms. The conclusions of physics are founded on the assumption that we cannot control the motions of individual molecules. In a mass of gas, or liquid, or in a solid, the molecules are free to move and do move. Their individual velocities and free paths vary considerably from each other. These motions and paths are un-co-ordinated—“helter-skelter”—if we like so to term them. Physics considers only the statistical mean velocities and free paths. The irreversibility of physical phenomena, the fact that energy tends to dissipate itself, the second law of thermodynamics, depend on the assumption that Maxwell’s demons exist only in imagination. We must appeal to experience now. There is no a priori reason why the phenomena of physics should be directed one way and not the other, for it is possible to conceive a condition of our Universe in which, for instance, solid iron would fuse when exposed to the atmosphere. In such conditions organisms would grow backwards from old age to birth, with conscious knowledge of the future but no recollections of the past. Experience shows, however, that phenomena do tend in one way—but this experience is that of experimental physics, so that for the latter science Maxwell’s demons do not exist. Now physiology has borrowed from physics, not only the experimental methods, but also the fundamental concepts of thermodynamics. The organism, therefore (so physiology must conclude), cannot control the motions of individual molecules, and so vital processes are irreversible. But we have seen that the processes of terrestrial life as a whole are reversible, or tend to reversibility. We must therefore seek for evidence that the organism can control the, otherwise, un-co-ordinated motions of the individual molecules.

The Brownian movement of very small particles of matter is so familiar to the biologist that we need not describe it. It is doubtless due to the impact of the molecules of the liquid in which the particles are suspended. Groups of molecules travelling at velocities above the mean hit the particle now on one side, and again on the other, and so produce the peculiar trembling which Brown thought was life. Now the particle must be below a certain size in order to be so affected. Are there organisms of this size? Undoubtedly there are, for many bacilli show Brownian movements, while we have reasons for believing that ultra-microscopic organisms exist. Also, on the mechanistic hypothesis there are “biophors,” the size of which is of the same order as that of the molecules of the more complex organic compounds. All these must be affected by the molecular impacts of the liquid in which they are suspended. Can they distinguish between the impacts of high-velocity molecules and those of mean-velocity ones, and can they utilise the surplus energy of the former? This has been suggested by the physicists. In Brownian movement, says PoincarÉ, “we can almost see Maxwell’s demons at work.”

The suggestion is not merely a speculative one, for it is well within the region of experiment. To prove it experimentally we should only have to show that the temperature of a heat-insulated culture of prototrophic bacteria falls while the organisms multiply.

Is it not strange that the biologists, to whom the Brownian movement is so familiar, should have failed to see its possibly enormous significance? Is it not strange that the biologists, to whom the distinction between the statistical and individual methods of investigation is so familiar, should have failed to appreciate this distinction when it was made by the physicists? Is it not strange that while we see that most of our human effort is that of directing natural agencies and energies into paths which they would not otherwise take, we should yet have failed to think of primitive organisms, or even of the tissue elements in the bodies of the higher organisms, as possessing also this power of directing physico-chemical processes?