Lastly, an example from the group of mammals may be cited. The metabolism of a dog in complete rest is examined for a prolonged length of time and we ascertain the values of the oxygen consumption, the carbon dioxide production, and the nitrogen elimination in the urine. Under the same nutritive conditions the animal is then allowed to work from time to time in a treadmill. During these working periods impulses of excitation are continually conducted to the muscles from the nervous system. It is now found that under the influence of the constantly recurring stimuli the quantity of nitrogen in the urine has only very slightly augmented, whereas the consumption of oxygen and the production of carbon dioxide has markedly increased.
What conclusions can be drawn from these instances of response to stimuli, of which any number could still be quoted? They show us, first of all, that a state or process existing under given conditions, is altered by the influence of the stimulus. This is a fact, however, which could be expected from the beginning and is self-evident, for stimuli are alterations in the vital conditions, and when these are altered the state of the system or the happenings thereof must also alter. The question with which we are here more closely concerned, however, is a somewhat more detailed characterization of the state or process itself, as well as that of alterations produced by the influence of the stimulus. The instances of response to stimuli already cited furnish us with information in both kinds.
In all these examples, the living processes occur with equal constancy and unaltered rapidity, provided a stimulus is not operative. Here, however, the gradual alterations, the result of development, must not be overlooked. An excellent example of this is seen in the eggs of sea urchin, where the development is readily perceptible. In all these instances, however, the condition is immediately changed by the influence of the stimulus. The previous state of constancy in the vital process is disturbed. The rapidity of its course is changed, being either increased or decreased, and the specific vital manifestations concerned are, therefore, augmented or diminished. We will now study the vital process with the methods of chemical investigation and consider the problem from the standpoint of metabolism. It may be noted here, that other methods, such as the transformation of energy or changes of form of the living system, would serve equally well as indicators for this purpose. In every instance there is a uniformity of the processes; the difference, however, is in the nature of the indicators and the terms used. The methods and the terms used in chemical investigation and description reach proportionately much deeper than those employed when the transformation, energy or the variations of form of the organisms are studied, and permit of the finest differentiation of the processes. The atomistic terminology is, for this reason, preëminently fitted for the description of vital processes. When we study the vital process metabolically, we can, as shown in the above-mentioned instance, divide the processes into a metabolism of stimulation in contradistinction to a metabolism of rest.
The comprehension of the metabolism of rest demands a closer consideration. On closer observation we must say that this much-used conception is merely an abstraction nowhere realized in a strict sense. In truth, there is nowhere in nature a metabolism of rest. No cell exists which in a mathematical sense remains for even two successive moments under absolutely the same external conditions. If we imagine a single living cell of the simplest kind living in a fluid nutritive medium, and if we suppose its body and surroundings so magnified that the single molecules and atoms were respectively of the size of cannon and rifle balls, the boundary between cell and medium would represent a battlefield, on which a heavy bombardment is constantly taking place. The rain of shot of food and oxygen molecules penetrating into the cell from the medium, would produce an explosion in the existing ammunition depots, now at one point, now at another, creating great breaches through which new masses of shot would reach the interior. The fragments of these exploding molecules would be flung out here and there into the medium and would stem, now at this, now at that point the besieging masses of shot. In this wild confusion on the whole boundary line between cell and medium there can be no question of rest or even equilibrium at any point. The human mind, superior to the material world as we may deem it, is yet always dependent upon the results of experience, and even in its highest flights cannot become wholly emancipated from the concrete objects. For this reason it is of great purport to conceive processes whose dimensions cannot be observed even microscopically, as enlarged and transformed to that method of expression most familiar to the human mind, namely, in the field of optical presentation. This method is of great help in aiding our understanding, and likewise here, even in the resting state, the cell is constantly exposed to local effects of stimulation, now at one point, now at the other. The conception of the metabolism of rest is, therefore, in a strict sense fiction.
Nevertheless, the conception of the metabolism of rest as an abstraction can be of value provided always that it is strictly and definitely limited. It must, for instance, not be applied to short periods of time. The continued local and temporary responses to stimulation constitute a mean value which, although composed of numberless small sub-threshold responses, we can still call a metabolism of rest. Weak stimuli have, however, as already seen, the property, provided their influence is constant, of effecting an adaptation to the stimulus on the part of the living organism, so that the stimulus becomes a vital condition for this state of the organism. Hence the continued existence of a vital process resulting from the constant action of stimulation is made possible. That which we are in the habit of calling metabolism of rest, would, therefore, be metabolism of stimulation, but one that is characterized by a constantly existing metabolic equilibrium.
This “equilibrium of metabolism” distinguishes the metabolism of rest from that form which is developed in response to temporary stimulation, in that every temporary stimulation has the effect that it disturbs the existing metabolic equilibrium for a longer or shorter time. This disturbance of the equilibrium of metabolism can in contrast to the metabolism of rest be termed “metabolism of stimulation.” In this, but only in this sense, can these two conceptions be placed in opposition and used to characterize the processes in the living organism. The conception of the metabolism of stimulation must always stand in relation to that of an equilibrium of metabolism characterized by a constantly existing metabolism of rest, just as the conception of stimulus can likewise only be defined relatively to that of vital conditions.
Nevertheless, the conception of the equilibrium of metabolism requires a somewhat more accurate definition before we can feel justified in using this term. Definitions are always trite, nevertheless they are the basis of all our thinking and a definite understanding is impossible unless we first clearly fix their contents. The history of theology and philosophy even to the most recent times furnishes a long line of instances in which the most eminent minds, for the want of fixed definitions of the conceptions which they made use of, failed to find a mutual basis for their ideas. Without a sharp definition every conception is a mere word, which each individual, according to his personal experiences and views, endows with a different meaning. To such conceptions we may apply Mephisto’s ironical comment to his pupil:
“Mit Worten lässt sich trefflich streiten,
Mit Worten ein System bereiten.”
The natural sciences, if they are to retain their reputation for exactness and precision, require the strictest and clearest definitions of all conceptions. If we seek to penetrate more deeply into the varied happenings in concrete conditions, we must reconcile ourselves to dry pedantic definitions. In the case of that of the equilibrium of metabolism indeed we have before us one of the most important conceptions in physiology.
The justification to speak of an equilibrium of metabolism arises from investigations of metabolism in mammals. The classical experiments of the previous century, as is well known, have shown that in the adult mammal receiving a necessary quantity of nourishment and in a state of rest, the intake and outgo of the constituent elements are the same. The carbon, hydrogen, nitrogen, oxygen, sulphur, phosphorus, etc., taken in during a lengthened period in the form of food and respired air, appear again in equal quantity, in other combinations, in the products of excretion of the organisms. Calorimetric experiments likewise show an equilibrium of the consumption and elimination of energy. If there thus exists an equilibrium of metabolism for the whole cell community, it is clear that the same must also apply to the individual cell, that is, for all living substance. The quantitative relations of the foodstuffs taken in, and the excreted metabolic products given off, are, however, merely a standard of the metabolism. We know that the former are used to build up new living substance and that the latter represent the result of disintegration of that previously existing living substance; for we find, as in the case of the plant, complicated protein combinations, which are built up from comparatively simple constituents of the food and are again broken down into comparatively simple substances. And so the building up and breaking down processes form the two great processes of metabolism, which with Hering[41] we can briefly call “assimilation” and “dissimilation.” In the terms assimilation and dissimilation are comprised the sum of all processes of construction and disintegration in the living organism. It is apparent that equilibrium of metabolism occurs when assimilation and dissimilation are equal. The formula A : D, that is, the relation of the sum of all assimilation to the sum of that of all dissimilative processes, is a factor of fundamental importance in the study of the course of the vital processes, for upon its value depends individual vital manifestation, and, in fact, the continuation of life. I have, therefore, designated the formula A = D “Biotonus.” The equilibrium of metabolism would then be characterized by the biotonus[42] of a living organism being equal to one. This would be the metabolism of rest of a system, whilst its metabolism of stimulation would consist in an alteration of the biotonus. But is this state of living substance strictly speaking ever realized?