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from a region of high to a region of low osmotic pressure; oxygen and nitrogen, with other elements of course, are withdrawn from the arterial blood stream for the purpose of the secretion, and carbon dioxide and other substances are given off to the venous blood and lymph.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 Amœba or Paramœcium 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:—
(2) | (1) | |||||||||
| : | a + b | : | a + b | : | a + b | : | a + b | : | a + b | : |
| : |
| : |
| : |
| : |
| : |
| : |
| : | c + d | : | c + d | : | c + d | : | c + d | : | c + d | : |
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 am + bn = cp + dr—the suffixes m, n, p, r, denoting the concentrations of a, b, c, and d—but after the stimulus the phase may be am1 + bn1 = cp1 + dr1. Now the element of the nerve substance (1) forms a system with the element (2). The condition in (2) is am + bn = cp + dr, and that of (1) am1 + bn1 = cp1 + dr1, 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.