General Physiology: An Outline of the Science of Life

The designation of a single cell-constituent as the specially differentiated bearer of heredity is wholly unjustified, the cell-protoplasm is of exactly the same value in this respect as the nucleus, and we must constantly return to the fact that in all living nature no instance is known in which a complete cell possessing nucleus and protoplasm does not always mediate hereditary transmission. To summarise, the character of every cell is determined by its peculiar metabolism. Hence, if the peculiarities of a cell are to be transmitted, its characteristic metabolism must be transmitted ; this is only conceivable when nuclear substance and protoplasm with their metabolic relations are transferred to the daughter-cells. This is true of the sexual reproduction of the higher animals, as well as of the asexual reproduction of unicellular organisms; in the former, however, the metabolism of one cell, the spermatozoon, is by the process of fertilisation combined with that of another cell, the ovum, into a single resultant, the metabolism of theoffspring that arises from the fertilised ovum ; the offspring hence possesses the characters of the two parents.

3. The Mechanics of the Transformation of Energy ly the Cell The third aspect in which the changes of a body make themselves manifest, besides those of substance and of form, is that of transformation of energy. The three aspects are inseparable and are the expression of all that happens in the physical world. Given one of the three in all its details, the other two would be known. This is true of both living and lifeless bodies, for both are physical systems and must obey the strict laws of all matter.

Unfortunately, as regards the transformation of energy in the living organism, our knowledge at the present time is but fragmentary. The beginning and the end are known, but between the two is the complex series of events in which the energy in its passage through the living substance takes part, and thus far only a few of these events have been discovered. But so much is evident: the changes of energy are just as manifold in their details as are the changes of substance and of form, and every kind of cell is characterised as much by the former as by the latter. It has been seen that the green plant-cell is that form of living substance which in a certain sense is the basis of all life now existing upon the earth's surface, in so far as it is the laboratory in which from inorganic materials organic compounds, which are the necessary vital condition of all other organisms, are manufactured. Hence, in outlining a scheme of the general circulation of energy in living nature, attention must be given to the green plant as the starting-point for the entrance of energy into the living physical world.

That form in which energy is introduced into the green plantcell is pre-eminently the energy of sunlight. Almost no chemical energy is introduced into the plant ; the chemical substances from which the plant constructs its living substance, namely, carbonic acid, water and the salts dissolved in it, are compounds which in this form contain almost no chemical potential. These compounds are transferred to substances possessing chemical potential only by the introduction of light mediated by the activity of chlorophyll in the green plant-cell. The affinities of carbon and oxygen, e.g., can be. made available only by the splittingup of carbonic acid, CO2, into carbon and oxygen. Energy is consumed in this process, and the amount required for it is supplied from the energy introduced by light into the plant-cell. It has, therefore, been said that all life is derived in direct descent from sunlight; and thus in a certain sense an exact scientific background is given to the ancient poetic worship of light and the sun by Asiatic and American races. But sober scientific consideration forces us to modify the above statement. If the idea that the sun's light-rays are the energy from which all the energy of the living world in the last instance is derived, may be expressed at all in this general form, it is true only for the conditions now prevailing upon the earth's surface. If we go back to the times when the living substance first appeared upon the earth, we shall doubtless be obliged to turn to chemical energy as that form of energy that was first introduced into the living substance.

Of course the living substance of the present day, like all substance, is finally derived, together with its energy, from the sun, for the earth is only a part of the sun's mass thrown off; but light can hardly be considered directly as that form of energy which effected upon the cooling earth the construction of those compounds, containing energy in the potential form, that are termed living substance. In. reality, at present it is not the light that directly accomplishes the splitting-up of the carbonic acid and the combination of the atoms of carbon, hydrogen and oxygen into the first product of assimilation, starch. This idea, which perhaps has been suggested by an inexact mode of expression, is wholly incorrect. In reality, it is only the chemical energy of certain compounds of the chlorophyll-bodies in the green plant-cell that does this. The energy of the light-rays alone can never split up carbonic acid, quite apart from the coupling of the atoms of carbon with those of hydrogen and oxygen into starch molecules. Light is indispensable only in so far as it is that form of energy which favours the rearrangement of the atoms in certain compounds of the chlorophyll-bodies, so that these atoms are able to enter into chemical relation with those of carbonic acid and thus decompose the latter. The energy of the light-rays, therefore, is first transformed into chemical energy, and it is the latter in the chlorophyll-bodies that effects the splitting-up of carbonic acid and therewith inaugurates

the endless chain of transformations of energy which characterise the life not only of the plants but also of the animals. The rdle of light is similar to that of the heat that is introduced ; heat is indispensable to life in both the plant and the animal body, and serves to increase the intramolecular vibrations of the atoms, so that the latter become inclined to rearrangements. But it is always chemical energy that effects these rearrangements. In other words, in the plant chemical energy must be already present in the chlorophyll-bodies, and only by the introduction and transformation of photic energy is this so increased that it can accomplish the first cleavage of the molecule of carbonic acid, which has such very important consequences. Where living substance with its chemical energy is not already present, the introduction of light cannot produce life. Thus, the chemical energy introduced into the organic world along with the first living substance in prehistoric times, even now continues to work in all living organisms, without ever having undergone a break in continuity. Life cannot be transferred from one organism to another without the transference of living substance containing chemical energy. It is a tiny quantity of both substance and chemical energy that is transferred in the microscopic egg-cell to the offspring, but it is sufficient to ensure the continuity of both. The chemical energy thus transferred makes reproduction possible, gives the impulse to the continual transformation of constantly greater and greater quantities of energy, in a certain sense by ferment-like action, and finally causes a powerful development of force in the adult organism. It is. the original capital with which the developing organism begins its dealings, and without which its existence would be impossible.

In this sense it can be said : that form of energy from which in the last instance all the work of the organic world is derived is chemical energy. The light and heat introduced act only by making chemical energy available. It is evident that this is equally true of animals and of plants. Out of the original chemical energy available in the plant not only is the manifold external work of the plant supplied, but a considerable quantity is stored up in the form of chemical energy in the organic compounds of the plant-body. These complex organic compounds afford food for the herbivore, while the flesh of the herbivore does the same for the carnivore. Thus, with plant-food energy comes to animals in chemical form and affords potentials for the performances of the animal body, which are distinguished so characteristically from those of the plants by their powerful extrinsic development of force. In fact, the chemical energy introduced into the animal body with the food forms the sole source of the energy of the animal body, with the exception of the small quantity of heat that acts from the outside upon all organisms. The proof of this fact has been afforded in the most

satisfactory manner by the calorimetric investigations of very recent times, especially by the very exact work of Rubner ('94). If upon the basis of calorimetric combustions the chemical energy of food be expressed in terms of heat, the food will yield just as many calories as an animal affords when all its production of energy is expressed in output of heat. The differences between the quantity of heat that is evolved by the combustion of food to substances lacking chemical energy, and the quantity of heat which the animal produces with like food during rest, are so small in the extremely delicate experiments of Rubner, that they fall wholly within the unavoidable technical limits of error. If it were at all necessary at the present time to prove the validity of the law of the conservation of energy for living nature, the best evidence would be given by Rubner's new calorimetric researches. The passage of energy through the organic world ends with the output of heat or mechanical work by the animal body. The animal body gives off to the outside no chemical energy that is capable of being used further, with the exception of that adhering to the egg-cell in reproduction. The substances that leave the animal body, such as water, carbonic acid, etc., are compounds that possess in their existing form no more chemical potential, and the introduction of light into the green plant-cell is necessary to enable the latter to create available chemical energy out of these substances. Thus, the circle of the changes of energy between living and lifeless nature is a closed one. Light makes available chemical energy in the plant-cell. Out of this chemical energy are derived all the chemical, mechanical, and thermal activities of the plant in a complex series.

The herbivore takes into its body with its food the chemical energy that is stored up in the organic compounds of the plant, and with the materials of its own body-substance becomes to the carnivore the indispensable source of chemical energy; from the latter is derived all the thermal, mechanical, and in special cases also the photic and electrical energy which the animal body gives off to the outside as heat, as mechanical energy of muscular movement, and as light and electricity. Out of the substances that leave the animal body, poor in mechanical energy, carbonic acid and water, the plant-cell under the influence of the light-rays creates anew chemical energy, and thus the endless circulation begins again.

I. The Principle of the Transformation of Chemical Energy in the Cell However clear the main outlines of the organic change of energy appear, its details are obscure. This is true partly because of our lack of knowledge of the metabolism of living substance, but largely because of the extremely slight development of the general theory of energy in physics and chemistry. The transformations of energy involved in events the material basis of which is known in fullest detail, are still wholly unknown. Thus, concerning the work performed in many chemical transformations, we do not know at all whether the mechanical energy thus set free is derived directly from the transformation of chemical energy, or after passing through other forms, such as heat, or electricity. The direct transformation of chemical energy into heat and electricity has been investigated exactly and in detail, but that of chemical into mechanical energy has thus far scarcely been studied. This circumstance, indeed, has frequently led to the mistaken belief that chemical energy can pass over into mechanical energy never directly, but only through the mediation of heat, an idea that is wholly without foundation. To make the subject still more difficult to understand there is the added fact that the conceptions of the individual forms of energy are not at all fixed, that, e.g., the expressions, molecular energy, mechanical energy, etc., are employed in very different senses, which results from the fact that the relations obtaining between the various forms are thus far not at all cleared up. Notwithstanding, it must be assumed that such relations, and even very close genetic ones, exist. It is, accordingly, evident that the more special energetics of living substance is at present one of the most obscure fields of physiology, only isolated and disconnected facts being known.

The general fact must be regarded as established, that all the work of the organism is based finally upon chemical energy. So far as is known at present, most of it is directly dependent upon this source at the moment of its occurrence. But the energy of many actions comes in a roundabout way. Pfeffer ('93) has recently made this fact especially clear for plants. Thus, it happens very frequently that in metabolism chemical energy first passes over into potential mechanical energy and is stored up as tension, to be transferred at the proper opportunity into the kinetic energy of mechanical work. Jumping-fruits and seeds of certain plants furnish examples of this. Here the chemical energy of growth first accumulates in the form of mechanical tension, and, when the fruit is touched, this passes over into vital motion, the fruit bursts open and scatters its seeds with great force. Analogous cases of the indirect derivation of work from chemical energy occur frequently among both plants and animals.

The chief forms in which the energy evolved by the cell is expressed, are mechanical energy and heat. The evolution of light and electricity is much more limited. In order to obtain an insight into the energetics of the cell, the chief principle that controls the transformation of energy in chemical changes must be recalled. This was formulated as follows: if in a chemical process affinities become united rather than separated, energy is liberated; if affinities become separated

rather than united, energy is absorbed.1 In the light of this, the fundamental principles of organic transformations of energy follow clearly from the well-known facts of metabolism. There exist in living substance certain compounds possessing strong chemical affinities. Other chemical affinities are introduced from outside into the living cell along with food and oxygen. These relatively simple substances that are introduced are employed for the construction of much more complex compounds, which we have termed living proteids or biogens. In- this process the chemical energy that is introduced passes over into the complex compounds in the form of potential energy, and helps to loosen their structure. E.g., it is known that by the introduction of oxygen the biogen molecule takes on an extraordinarily labile constitution, i.e., its intramolecular heat becomes very great. As a result of this the molecule tends toward decomposition, and explodes, partly spontaneously and partly upon slight external stimulation. This explosive decomposition depends upon a re-arrangement of the atoms, whereby, as in all explosive bodies, within single atomic groups stronger affinities become united than were previously united in the labile molecule. Therefore, as a whole, dissimilatory processes must be associated with a considerable production of energy. The compounds that are derived from this decomposition of the biogens and leave the body, such as carbonic acid, water, etc., contain scarcely perceptible quantities of chemical potential, while the compounds that remain in the body, the residue of the biogens, again possess chemical affinities for food-stuffs and oxygen, and employ them in uniting with the latter. The energy thereby made available is employed again for loosening the biogen molecule, and thus the chain ends.

The principle upon which it is based accordingly appears clear : there is a continual storing up of potential chemical energy and a transference of it into other forms ; the source of it is the food and the oxygen ; the original capital is the chemical energy that every minute droplet of living substance has carried over from its ancestors; and the result is expressed in the work accomplished by the living substance. The relations as regards energy that develop in living substance under the influence of stimuli are comprehensible, in their general outlines, upon the basis of these facts. Those cases are simplest in which the stimulus causes an excitation of dissimilation. As has already been seen,2 this process consists of an augmentation of spontaneous processes. The potential energy that is stored in the labile biogen molecules is to a certain extent spontaneously transformed into actual energy, the atoms being rearranged and combined with one another by stronger affinities, and an explosive decomposition simultaneously occurring. It is easily comprehensible that certain stimuli may increase directly the intramolecular 1 Cf. p. 215. 2 Cf. p. 474.

motion of the atoms in the biogen molecule, and thereby give greater opportunity for rearrangement and explosive decomposition ; the augmentation of the processes under the influence of certain stimuli needs no further explanation. Those cases of reactions where there is a depression of dissimilation also scarcely need further discussion, for all those stimuli that diminish the intramolecular motion of the atoms in the biogen molecule, or hinder the rearrangement and combination of definite atoms in any way, such as cold or narcotics, must evidently diminish the normal work of the cell. But not all the performances of living substance are associated with the dissimilatory phase of metabolism. Many important ones go hand in hand with the assimilatory phase. Hence, stimuli that excite assimilation, such as increased food, will augment such performances, since they afford a greater opportunity for the formation of new biogen masses; and, vice versa, stimuli that depress assimilation will produce the opposite effect. Those vital phenomena that are associated with assimilation and are augmented by stimuli that excite this process, have been greatly neglected by investigators in comparison with the more evident phenomena associated with dissimilation, and they deserve special consideration in the future.

This idea of the action of stimuli does not imply that the energy that is manifested in definite work as the result of a stimulation is always derived directly and solely from the excitation or depression of one or another link in the metabolic chain. According to our idea, the satisfying of the free affinities of the residue of the biogen molecule, i.e., its regeneration, follows directly its explosive decomposition. Hence, under certain circumstances there is contained in the reaction not only the energy set free by the decomposition of the complex compounds, but also the energy that becomes actual in the processes that result directly from the decomposition, and the same is true of other cases of reactions. Thus, all the elements of the energetics of the cell are extraordinarily closely interwoven. This follows necessarily from the facts of metabolism above discussed. The very great difficulty of following in their details the more delicate transformations undergone by the energy in a given work, whether spontaneously or upon stimulation, is evident ; and hence, with the extremely few investigations that have been carried on in this field thus far, it is at present impossible to determine with any certainty the energetics of even the more evident performances of the cell, such as the production of light or electricity and the evolution of mechanical energy in the various kinds of movement. To study in detail the extremely interesting history of the energy in the various internal and external labours of the living cell will be one of the most stimulating tasks of the physiology of the future.

Although thus far but few investigations have been made by physiologists upon the mechanics of the transformation of energy in living substance in general, this is not true of one particular class of these phenomena. This class comprises the movements of contraction and expansion. The mechanics of muscle-contraction especially, in which energy is developed with most remarkable and most astonishing power, has from early times engaged very actively the attention of physiologists, and the number of theories that have been formed regarding the mechanics of muscular movement is only a little smaller than the number of investigators who have studied the problem thoroughly. An interesting chapter in the history of human thought is reflected in these theories from the time of Galen down to the present day, and it is pleasing to one's historic sense to trace these theories from their very naive beginnings. Whoever is interested in this bit of physiological history will find the literature of the older theories down to the preceding century collected by Haller (1762). Hermann ('79) has given the essentials of the later theories in his Handbuch der Physiologic, and the newest views, so far as they possess interest, are collected and critically examined in a work that has recently appeared,1 which considers the old problem from the comparative, cell-physiological side.

Without a doubt, of all the activities of organisms, muscle-work is that in which the greatest transformation of energy takes place in the shortest time. The quantity of energy that is set free in muscle-activity, as is well known, is astonishing. Hence the question presents itself : of the energy introduced into the body what portion affords the energy that is thus set free, in other words, where is the source of muscle energy to be sought ? It is evident that the source must be chemical energy, for the animal-body performs its labours by means of chemical energy exclusively. But which of the food-stuffs introduced into the body afford by their transformation the chemical energy necessary to muscle activity ? Is it the proteids, or is it the carbohydrates and the fats ?

An active contest, which very recently has become augmented, has been carried on over this question. The original and very clear theory of Liebig ('57, 70) that proteid as the chief constituent of muscle must be the source of its work, was attacked during its author's lifetime, and it has since been thought for decades that in place of Liebig's view the correct solution of the problem had been found. The argument that led to this idea, which has prevailed to the present time, is interesting. It was said : if the source of 1 Cf. Verworn ('92, 1).

muscle-energy lies in the decomposition of proteid, the latter must be increased by extensive muscular activity. Since, now, it was believed that an absolute measure of the extent of proteid-decomposition in the body is to be found in the excretion of nitrogen in the urine, the question would appear to be decided by a comparison of the nitrogenous contents of the urine during rest and during extreme muscular activity. If the nitrogen were increased during work, the increase could be derived only from increased proteidtransformation ; if it remained the same, the source of muscleenergy was not to be sought in proteid but in non-nitrogenous food-stuffs. The problem was, therefore, presented in a very clearcut form, and the decision could not be left to itself. Fick in company with Wislicenus ('65) showed upon himself, and Voit ("70, '81) upon the dog, that the excretion of nitrogen in the urine is not markedly increased by intense muscular activity.

The question thus appeared to be answered yery precisely. It was concluded that the decomposition of proteid could not be the sole source of muscle-energy. It was argued that of the non-nitrogenous food-stuffs the carbohydrates especially, and eventually the fats, must come into consideration ; and it was known that with intense muscular activity the glycogen stored in the muscle disappears, and accumulates again during rest. The argument appeared wholly unobjectionable, and the view was generally accepted that muscle-energy is afforded chiefly by the decomposition of carbohydrates.

But the view that proteid does not take the chief part in the extreme activity of the muscle-cell necessarily appeared parodoxical to all who were at all familiar with the general vital characteristics of living substance. Proteid is the substance with the formation and decomposition of which life is inseparably associated, and hence it seemed very remarkable that in augmented vital activity, such as is represented by intense muscular movement, the transformation of proteid was the same as during rest. Pfliiger could not sympathise with this view. In a series of striking researches, supported by experiments free from objection, he recently attacked it, and sought to establish proteid-decomposition as the chief source of the energy of muscle. It was already known to Voit that dogs can maintain themselves upon a meat diet alone. Pfliiger ('91), therefore, fed a dog for many months exclusively with meat, as pure arid free from fat as possible, and made him perform several times every day for weeks very difficult labour. The animal showed continually " very extraordinary strength and elasticity in all his movements." Since the slight traces of carbohydrates and fat contained in the meat need not be considered in nutrition, it was proved that all the energy produced during the hard labour of the dog was derived from the transformation of proteid. But in order to discover whether the proteid served simply as a

compensatory source of muscle-energy while carbohydrates and fats were lacking in the food, Pfliiger ('92) carried on a series of experiments with mixed food. These led to the important result that with a food composed of proteid, carbohydrates, and fats, the quantity of the two latter substances that is destroyed in metabolism depends wholly upon the fact whether much or little proteid is fed. " In general, the quantity of carbohydrate and fat that undergoes destruction is smaller, the greater the income of proteid." The undestroyed carbohydrate and fat are changed into body-fat and accumulate as reserve-material, while, as is well known, the introduced proteid, however much it may be, is destroyed even to an excessively small fraction. It may, therefore, be said : " the need of food is satisfied first by proteid." Proteid is the " primitive food," carbohydrate and fat are simply a " compensatory food " employed during a lack of proteid.

Although in accord with this it is established beyond doubt that muscular work is made possible primarily by the decomposition of proteid, the equally undeniable fact, that the excretion of nitrogen in the urine does not appear to be correspondingly augmented by the most intense muscular activity, must excite surprise. In this connection another experiment of Pfliiger deserves attention. Pfliiger found that with pure proteid food and with an equal quantity of food during rest and during labour the excretion of nitrogen is increased by muscular activity very inconsiderably, and under certain circumstances not at all. Nevertheless, all the working-power must be derived from the decomposition of proteid alone, since no carbohydrate and fat are fed. With an excess of proteid such a remarkable phenomenon would be directly comprehensible, if we were to bear in mind that even during rest all proteid introduced into the body is decomposed ; for if, as has been shown, the energy of muscular work is derived from the proteid decomposed, it might be concluded that an amount of proteid equal to that consumed during activity has been saved elsewhere in the body. This would be supported by the fact that all proteid eaten beyond a certain quantity is a luxus consumption, and is, therefore, available whenever needed. But if it be borne in mind that, as Voit ('60, '66) has shown, in hunger the excretion of nitrogen in the urine of the dog is increased by labour in the treadmill either not at all or only inconsiderably, this conclusion cannot be drawn, and the above explanation of the non-increase of nitrogen excretion does not suffice.

There still remains one possibility, which Pfliiger has only touched upon, namely, that during labour a transformation of proteid takes place in the muscle without the nitrogen of the transformed proteid appearing in the urine. This idea, to which we are forced by the facts, although directly contradicting an old-established physiological dogma, is not so wholly paradoxical as at first sight it appears. The dogma, which has retarded not a little the advance of knowledge of vital processes, and the origin of which is due simply to the fact that investigators devoted themselves so exclusively to the vital phenomena of higher animals, is expressed in the statement that the excretion of nitrogen in the urine is an absolute measure of the proteid-transformation in the body. Such an assumption is quite unproven, at least in this form.1 It may be said with a certain amount of justification that the nitrogen excreted in the urine is derived from the decomposition of proteids. But there is absolutely no justification for maintaining, vice versa, that all the nitrogen of the proteid transformed in the body appears in the urine. The fact that all food-proteid beyond a certain quantity is transformed in the body into groups of atoms, the nitrogen of which is excreted in the urine, cannot be generalised, and especially it cannot be applied to the decomposition of organised proteid, the biogens. As is well known, both non-nitrogenous and nitrogenous groups of atoms are derived from the decomposition of the biogeii molecule. The non-nitrogenous groups such as carbonic acid, water, lactic acid, etc., leave the body at once. But the assumption is not required that all the nitrogenous groups also leave the body at once. It is conceivable that under certain circumstances the nitrogenous residue becomes regenerated into a complete biogen molecule at the expense of the food-stuffs and the oxygen, or in hunger at the expense of the reserve-substances. There would then be a decomposition of biogens which would result in no excretion of nitrogen in the urine.

There is no fact that disputes the view that in muscle-activity the biogeii molecule is decomposed, and that, in general, the nitrogenous residue regenerates the lost non-nitrogenous groups of atoms at the expense of the food. Such economy with the costly nitrogen would be wholly in accord with the methods of the organic household. This idea, which has been here put forward simply as a possibility suggested by the facts, upon more careful consideration seems even probable. Before all else, it is in harmony with our general physiological views upon the nature of the vital process, and it accords with the ideas that must be formed, upon the basis of innumerable facts, regarding the events occurring in living substance. As is well known, the proteids are the chief constituents of living substance, and they are also the sole organic substances by the transformation of which alone the work of the living organism can be maintained. Moreover, as has already been seen,2 of all other substances that occur in the cell some serve for the construction of the proteids and biogens, and some are derived from the transformation of them. In other words, there can be no doubt 1 Cf, p. 175. 2 Q/: pp. 163 and 479.

that life is associated most closely with the construction and destruction of certain highly complex proteids, which for this very reason we have termed biogens. If this be granted, it would be in the highest degree paradoxical, if an increase of the vital process, and so enormous an increase as is expressed in intense muscular activity, should not be necessarily associated with an augmentation of the biogen-transformation in the body. Hence, to the end of his life Liebig, the old master of physiological chemistry, believed indefatigably that we ought to defend the view that the proteids are the substances the decomposition of which constitutes the source of muscle-energy ; and hence also Pfliiger, one of the most far-seeing of the physiologists, combats again to-day the view that muscle-activity is able to take place without the decomposition of proteids. But if, during muscular activity, an increased transformation of biogens takes place, and if, nevertheless, no more nitrogen is then excreted than during rest, the further conclusion is necessary that the nitrogenous residue is again regenerated into the complete biogen molecule. Without such a possibility the simplest and most general vital phenomena cannot be understood. How, for example, can the fact of growth, the fact that living substance is formed from other living substance only, be otherwise conceived than in accordance with the idea that the biogen molecule is capable of uniting to itself definite atoms and groups of atoms, and thus gradually grows into a polymeric molecule ? Polymerisation depends upon the successive introduction of groups of atoms. Further, regeneration rests in principle upon the same processes as growth.

The fact of complete recovery after total fatigue, also, and many other fundamental phenomena of living substance, presuppose unconditionally the regenerating power of the biogen molecule. It is, however, especially important that the idea here developed is in accord with the two apparently irreconcilable views upon the source of muscle-energy. According to this idea, both the proteids and the carbohydrates of the food may serve as the source of this energy. If muscular activity is focussed in the decomposition and reconstruction of the biogen molecule, and if in its decomposition only non-nitrogenous groups of atoms leave it, it is evident that only non-nitrogenous groups of atoms also are employed for its reconstruction. The facts prove that the proteids as well as the carbohydrates of the food can serve for this, although, as Pfliiger has shown, with mixed food and sufficient proteid the proteid is preferred. Thus the incontestable fact that in muscular activity the proteid food can be protected to a certain degree by the carbohydrates, is comprehensible ; and the claims that the carbohydrates on the one hand, and the proteids on the other, are the source of muscle-energy, are equally justified. The two substances can play the same rdle, however, only by placing at the disposal of the

biogen-residue non-nitrogenous groups of atoms. The vital process in muscle is the same, whether it draws its material from the proteid of the food or from the carbohydrate and fat. The general validity of the idea here presented of the source of muscle-energy will be more apparent after the problem of the mechanics of the special changes of energy in contractile movements has been examined in detail. Without considering singly the almost innumerable theories that have been put forward regarding the mechanism of musclecontraction, we can distinguish among the more important views expressed in the later physiology two essentially different groups. There is general unanimity in the belief that muscle-energy has its source in chemical energy, and, if the ideas here expressed upon the vital process be accepted, there can be no doubt about this. But, while according to some physiologists the mechanical energy of musclework comes directly from the transformation of chemical energy, according to others it comes by a roundabout way through heat. The former view is defended by Pfluger (75, 1), Fick ('82, '93, 1) and others,1 the latter especially by Engelmann ('93). A theory by the Gottingen philosopher, Elias Miiller ('91), which derives the one kind of energy from the other indirectly, first through heat and then through pyro-electricity, has not yet appeared in a complete form.

For the starting-point in our consideration we may best choose Engelmann's thermodynamic theory of contraction. Engelmann sees a difficulty in the direct derivation of muscle-work from chemical energy in the following circumstances. If from the amount of energy produced by muscle, upon the assumption that this is afforded by the combustion of carbohydrates, and upon the basis of a combustion heat of 4,000 calories per gram of carbohydrates, the quantity of substance be computed that is necessary to the work performed by the muscle in a single contraction, it is found that this quantity is surprisingly small in proportion to the mass of the muscle. Engelmann finds that approximately only one four-millionth of the whole mass can be considered as yielding the energy afforded in a single contraction. With the great amount of water in the muscle, which he assumes at approximately 70 — 80 per cent., he regards it as incomprehensible how such an enormous, passive mass can be put into motion by the direct effect of the chemical energy of such a small quantity of effective substance working locally. He regards this as possible only when the chemical energy is first transformed into heat, which can be distributed everywhere, and, therefore, is not limited in its effect to 1 Of. Verworn ('92, 1).