Nobel Lecture, December 12, 1923

The Mechanism of Muscular Contraction

In investigating the mechanism involved in the activity of striated muscle two points must be borne in mind, firstly, that the mechanism, whatever it be, exists separately inside each individual fibre, and secondly, that this fibre is in principle an isothermal machine, i.e. working practically at a constant temperature. There are several ways of studying this machine – the mechanical, the thermodynamic, the chemical, and the electrical, and of course any combination of these. In the case of nerve, much information has been acquired from a study of its electrical properties especially recently in the hands of Keith Lucas, Adrian, and Erlanger and Gasser. In the muscle fibre, however, as distinguished from muscular tissue in general, comparatively little has been discovered by studying the electric change. The apparent exception of the heart is not a real one, since here the electric change has been used to analyse, not so much the behaviour of the individual fibre – that is, of the ultimate mechanism itself – as the distribution and interconnection of the fibres to form the complete working organ. We will not therefore consider the electrical phenomena further in our discussion of the mechanism of the muscle fibre.

Much investigation has been devoted in the past to the mechanical response and characteristics of muscles, and it might have appeared that this subject is to some degree worked out and unlikely to yield further results of value. Actually, however, in combination with thermodynamical observations and considerations, much information has been derived recently from a study of the mechanical output and behaviour of muscles. Indeed, in the last two or three years the investigation of the connection between the rate of shortening, the work done and the heat production has pointed to new, hitherto unsuspected, mechanisms in muscle which are of considerable theoretical interest and practical importance.

The chief advances, however, during recent years have come from a study of the thermal and the chemical changes which occur in excised muscle. These two sides of the investigation are the ones which Professor Meyerhof and I will discuss today.

One of the fundamental characteristics of striated muscle, and the one involving the greatest difficulty in investigation, is the great rapidity with which changes take place in it. There is no doubt that ultimately the muscle is a chemical mechanism, in the same way for example as a Daniell’s cell or an accumulator is a chemical mechanism. If we were aware of all the chemical events, we should know all that was necessary about the machine which we are studying. Unfortunately, the investigation of chemical events is a slow and laborious process. Undoubtedly lactic acid, as Fletcher and Hopkins showed some fifteen years ago, is an essential part of the machinery, but it is impossible to measure the production and removal of lactic acid instantly and contemporaneously during and after a single unit of muscular response. It is necessary to evoke a long series of responses and finally to study the gross changes of accumulation or removal of the acid. Attempts have been made to follow the chemical processes involved in muscular activity by studying the changes of hydrogenion concentration by physical instruments. This would appear to be more hopeful than the possibility of quickening up the study of the reactions by ordinary chemical means, but unfortunately – so far – it has been completely unsuccessful. The instantaneous and contemporary study of the events occurring inside the muscle fibre appears to be possible only in two ways, the mechanical and thermal. As regards the mechanical, the technique is obvious, namely, connecting the muscle to suitable recorders, ergometers and levers. The mechanical changes occurring in muscle are, however, only the end-products of activity, and if we wish to get inside the mechanism, it is necessary to study some inter-mediate process, something occurring between the stimulus and the response itself, something associated with the chemical events which evoke contraction. This is provided by the investigation of the heat production. It is obvious of course that the picture provided by thermodynamics is only a partial one; the certainty, however, with which the principle of the conservation of energy may be applied, gives us firm ground on which to start our investigations, and there would seem to be no doubt that the outline provided by thermodynamics, once established, must remain, and must finally have the complete chemical picture painted into it. The advantage of the study of the thermodynamics of muscle is that heat may be measured in absolute units, rapidly and at once, and the time-course of its evolution analysed by suitable means.

In the study of the thermal changes the most consistent and valuable results have been obtained by utilizing the isometric contraction of the sartorius muscle of the frog. The sartorius muscle is a very suitable medium for this investigation, insofar as it is practically of uniform cross-section and consists of straight fibres running along its length. The isometric contraction has the advantage, firstly, that energy is not liberated in it in any other form than heat, so that no complications arise by having to sum the thermal changes with the mechanical work, and secondly, that in it movements of the instruments are prohibited, which on the small scale of temperature with which we are dealing is of value in avoiding errors due to temperature differences along the muscle.

The fundamental difficulty in myothermic observations is the smallness of the changes involved and their rapidity. In the muscle twitch of a frog’s sartorius at 20°C the rise of temperature is not more than 0.003°, and the time occupied in the earlier phases (as distinguished from the recovery process) is only a few hundredths of a second. The first requisite therefore is a very sensitive thermometric apparatus and great freedom from temperature changes, the second is extreme rapidity and lightness in the recording instruments. Neglecting for obvious reasons the use of ordinary mercury thermometers, there are two possible methods available, those of the resistance thermometer and the thermopile respectively. The resistance thermometer has not been employed successfully in myothermic observations. Calculation with the requisite physical constants shows the existence of a certain fundamental difficulty, which is confirmed by actual experiment. Were it possible to use the resistance thermometer, it would be exceedingly advantageous, as such an instrument may be made very small and light, so that it will respond with great quickness to the temperature changes in its neighbour-hood. Moreover, unlimited sensitivity may be obtained by increasing the current in the resistance wire. The fundamental difficulty is that heat is thereby produced in that wire, which is conducted into the muscle and warms it up, causing serious disturbances of the zero, and enormous negative deflections when the smallest movement of the muscle occurs. I have attempted recently to use a resistance thermometer for myothermic observations and found it completely impossible, owing to the errors produced by the heat production in the resistance thermometer itself. There remains, there-fore, only one method, that of the thermopile, which we will now discuss.

It is possible to make a small light thermopile, suitable for myothermic observations, containing one hundred couples, each providing 50 micro-volts for a difference of temperature of 1°C. With a suitable sensitive galvanometer this gives us a scale of temperature in which 1°C is about one kilometre in length. Ample sensitivity, therefore, is available. Such thermopiles are laborious to make by the ordinary method of soldering the wires together, though practically all the work hitherto recorded has been done with instruments thus constructed. Recently, however, an ingenious device has been published by Hamilton Wilson, by which a continuous piece of constantan wire is coated with silver in successive sections by electroplating, and each pair of junctions between a silver-plated and an unplated portion acts as a silver-constantan couple. By this device very small, light thermopiles may be constructed with great ease, and recently Drs. Fenn and Azuma have used such thermopiles in their work with me.

The developments of the technique appear to lie in refining and lightening hermopiles, in improving their sensitivity, and in the use of more sensitive and rapidly moving galvanometers. It may conceivably be possible to amplify the electromotive force produced by such thermopiles, and so to use a galvanometer of short period in order to quicken the recording. The possibilities already available of myothermic investigation are mainly due to improvements in galvanometers and thermopiles.

It is not practicable to register the changes of temperature in a muscle as they occur, without lag or loss : the recording instruments are too slow, they possess too great a heat capacity, the flow of heat is not rapid enough and the galvanometer – which must be sensitive – has too long a period. It is necessary to carry out an analysis of the results obtained, preferably after photographic recording of the galvanometer deflection. The possibility of analysing the time-course of the evolution of heat in a muscle contraction depends upon certain fortunate physical properties of the system employed. The conduction of heat, the relation between e.m.f. and temperature, the movements of the galvanometer, its dynamics, the control on it for small movements, and its damping, indeed, all the factors connected with the deflection of the galvanometer resulting from the change of temperature of an object in contact with the thermopile, are governed by linear differential equations with constant coefficients. It is not necessary to know what these coefficients are, as I shall show shortly – they can be eliminated by a control experiment – it is essential only that the system employed should possess this general property. Its consequence may be expressed in a very simple form. If there be two productions of heat recorded separately, then the deflections produced, if summed together, are the same as the single deflection which would have been produced if the two heat productions had been summed together. If the damping had been proportional to the square of the angular velocity of the magnet system, or if the conduction of heat had been proportional to the square of the temperature difference, this fact would not have been true. Expressing the matter mathematically: if y = f (t) be the equation relating the deflection y to the time t for a certain heat distribution* H, and y’ = f’ (t) be the equation for another heat distribution H’, then for a combined distribution of heat, H + H’, the deflection will be Y = y + y’ = f (t) +f ‘ (t). This property of the system seems to be a very exact one, and it makes possible an analysis of the evolution of heat which would otherwise have been very difficult.

Owing to the heat capacity of the recording instruments and the lag in the conduction of heat and in the galvanometer deflection, the readings actually obtained with myothermic apparatus are considerably smaller than those calculated from the physical data of thermoelectromotive force, number of junctions, and galvanometer sensitivity. Indeed the calculation of heat production directly from such data gives results very far from the truth, and it is impossible without some direct method of calibration to compare work expressed in mechanical units with heat expressed in galvanometer deflections. Fortunately it is possible to make a direct calibration of the instruments by liberating in the same muscle, in the identical position on the thermopile at the close of an experiment, a known amount of heat. A muscle must first be killed by chloroform, and then an alternating current of known strength must be passed for a known time through the measured resistance of the muscle, so that a definite amount of heat may be liberated, and the resulting deflection of the galvanometer read. A comparison of the two gives h the value in absolute units (calories or ergs) of one scale division of the galvanometer. There are various technical difficulties in this calibration which need not be discussed now, but in one modification or another it serves as the basis of all experiments relating heat to work. To some of these I will refer later. I wish to speak at present rather of the analysis of the time-course of the evolution of heat in muscle when stimulated. An amount of heat liberated suddenly at a given time leads to a certain deflection of the galvanometer, y = f(t), which rises to a maximum and falls slowly to zero again owing to conduction away of the heat, etc. A live muscle would give the same shape of deflection, if the heat produced in it were liberated at, or immediately after, the moment of stimulus. In point of fact the “live” deflection differs largely from the “control” one, a fact which can be explained only by supposing that the heat production in the live muscle is not instantaneous at the beginning, but distributed in time, there being production or absorption of heat later on. I may say at once that neither I nor any of my colleagues have ever found an absorption of heat at any stage in the process, so that apparently nothing but production of heat need be taken account of. One of my earliest observations on the subject was that the galvanometer deflection persists much longer in a live muscle than in a control experiment: it remains away from its zero for periods up to ten minutes, whereas, if the production of heat were instantaneous at the beginning, it would be back to its zero in two or three minutes. This phenomenon can be due only to a delayed production of heat, and I found that this “recovery” heat, as we called it, is appreciable only in oxygen, being abolished by keeping the muscle in nitrogen, or by previous exercise violent enough to use up the oxygen dissolved in the muscle. My original analysis was rough and revealed little but the facts themselves and their order of quantities. It certainly, however, did establish the existence of a recovery heat production, which it was natural to associate – rightly, as it has proved since – with the oxidative removal of lactic acid discovered by Fletcher and Hopkins. A rough estimate of the magnitude of the recovery heat production made it approximately equal to the total initial heat. This estimate appeared to answer unequivocally a question long debated, on the fate of lactic acid in the recovery process. Fletcher and Hopkins had found that lactic acid is removed in the presence of oxygen, though the same muscle at the end of the recovery process can liberate during exercise or rigor the same amount of lactic acid as before. Was lactic acid removed by oxidation, or by restoration to the precursor from which it came? Previous experiments of my own had shown that the production of one gram of lactic acid in rigor leads to the liberation of about 500 calories. Experiments by Peters had proved that the production of 1 gram of lactic acid in exercise, or in exercise followed by rigor, leads to the liberation of about the same quantity of heat. Hence, if the recovery heat were equal to the initial heat, the oxidative removal of one gram of lactic acid would lead to the production of about 500 calories, which is less than 1/7th of the heat of oxidation of the acid. The conclusion, which was not universally accepted at first, seemed to me to be inevitable – that the lactic acid is not removed by oxidation. This conclusion has been amply confirmed by the later experiments of Meyerhof which he will himself describe.

In a large mass of muscle deprived of its circulation, the rate at which the recovery process can go on, after severe stimulation, depends on the rate at which oxygen can reach the fibres by diffusion. Such are the conditions in calorimetrical experiments. The myothermic method, however, employing small thin muscles subjected only to very light stimulation makes it possible to follow the recovery process under conditions where the rate is quite uninfluenced by any possible lack of oxygen. In such small contractions there is sufficient oxygen already dissolved inside the muscle to account for far more heat than the total amount liberated in recovery. It is possible therefore to follow the chemical dynamics of the recovery process uninterfered with by considerations of oxygen supply. The study of the actual time-course of the recovery heat production has required more elaborate and careful experiments than I made alone in 1913, and since the War, I have had the cooperation in this and other matters of my friend W. Hartree, whose skill in experimental work and calculation has made it possible to reach a degree of certainty in the analysis which I could never have attained alone. By photographic recording and accurate numerical analysis of the deflection for ten minutes after stimulation, it has been possible to describe the whole of the time-course of the heat production in recovery. Its absolute magnitude is 1.5 times the total initial heat; its rate is influenced by temperature in the way usual in biochemical reactions. It starts from a low rate, rises to a maximum, and declines to zero again. It seems to occur with a velocity approximately proportional to the square of the concentration of the bodies whose removal constitutes recovery. Taking Meyerhof’s value for the heat per gram of lactic acid, we find that 1/5 to 1/6 only of the lactic acid is oxidized in recovery.

It is clear that the recovery process is a fundamental part of the whole mechanism of muscle. As we shall see later, oxygen is used only in the recovery process, a fact which has led to a new conception of the nature of the muscular machine.

The analysis of the recovery heat production is comparatively simple because its evolution is slow. It is desirable, however, also to analyse the production of heat in the earlier phases of contraction, a far more difficult matter. After a single shock the muscle shows two phases of contraction, namely, the development and the disappearance of the mechanical response – contraction and relaxation. Tetanus shows three phases, contraction, relaxation, and maintenance. It was desirable to analyse the chemical break-down processes associated with each of these phases. It will be simpler if I describe phenomena actually seen and recorded with the instruments.

A muscle is stimulated, the galvanometer deflects, a curve is recorded on a moving photographic paper. A control curve is made later, after the muscle is dead, for which a known small amount of heat is liberated rapidly, e.g. in 0.1 second, and another deflection is recorded. It is found even in the earliest phases, long before the development of the recovery process, that the two curves differ from one another. The curve for the live muscle rises less steeply and falls less steeply than the control curve, a fact which can be due only to a spreading out of the heat production. The curves do not differ largely from one another because the whole time occupied in the initial phase is so short compared with the time relations of the galvanometer and ther-mopile themselves. The difference, however, is sufficient to make the analysis practicable, and by keeping the muscle at a low temperature it is possible to slow down the events and to attain a greater degree of accuracy in the analysis. The result that appears is that during the development of the contraction there is a large outburst of heat, during the maintenance of the contraction there is a continued production of heat, reaching a constant rate as the contraction is prolonged, and a comparatively large and sudden evolution of heat during relaxation. An excited muscle behaves like an excited electromagnet: energy is required to magnetize the iron and to make it develop its pull; energy is required to cause it to maintain its magnetic condition and to continue its pull; heat is liberated when the magnetic condition, and the energy associated with it, disappear as the current is cut off. In the muscle, energy is required to set up the contraction, and, as we shall see later, more energy is required if work be done. Energy is needed to maintain a contraction, as, indeed, we know in our own bodies when we try to hold a weight for a long time. During relaxation the potential energy of strain possessed by a muscle during contraction has to disappear, and we find it as heat.

The most important point brought out by this analysis of the initial heat production is that relating to the influence, or rather to the absence of influence, of oxygen. The essential conclusion can be drawn without any analysis, merely by comparing the curves of deflection with and without oxygen. The proof that oxygen has no effect whatever on the time-course of the initial heat production complements an observation by my friend Weizsäcker, working with me in 1914, that the presence or absence of oxygen has equally no effect on the magnitude of the initial heat production. No difference whatever can be detected between the curves obtained: (a) from a muscle in pure oxygen, and (b) from one which has been deprived of oxygen in the most rigorous manner for several hours. The conclusion is important and supplements the observations previously described on the recovery heat production. Oxygen is not used in the primary breakdown at all: it is used simply in the recovery process. A muscle is like an accumulator, which can be discharged without any kind of combustion or any kind of provision of energy from without: it requires external energy only when it is being recharged. It has long been known, of course, that muscles can go on working for some time in the absence of oxygen, but it was open to anybody to suppose that the processes in the presence and in the absence of oxygen were different. So they are, to the extent that recovery takes place in the one case but not in the other, but the complete absence of any effect of oxygen on the initial processes of contraction shows that those initial processes are identical in both cases. The analogy of the accumulator is exact.

These conceptions arrived at by studying isolated muscle have an obvious application to man. One knows that after violent exercise one breathes heavily for some time: the more violent the exercise, the longer one’s respiration is laboured. If a man runs a hundred metres as fast as he possibly can, he requires about four litres of oxygen extra, in the succeeding five minutes, to enable him to recover from his effort. In other words 11 seconds of exercise has caused him to use in recovery as much oxygen as he would require for about fifteen minutes at rest, as much oxygen as he could get during one minute of the most laboured respiration. The matter is a simple one to investigate by means of Douglas bags and gas analysis. One takes a reading of the resting oxygen consumption, and during the recovery process one measures the oxygen used in excess of the resting value. By employing a series of bags, and collecting the expired air for various short intervals during recovery, it is possible also to study the time-course of that process. Unlike the case of the isolated muscle on the thermopile the rate at which oxidative recovery occurs in man is determined largely by considerations of oxygen supply and not merely by the actual chemical reactions. At the end of exercise, when the oxygen consumption is at its maximum, it begins immediately to fall, and after moderate exertion reaches its resting value in about five minutes. After severe exercise, however, it remains high for a long time, only reaching its resting value after an hour or two of recovery. This condition of prolonged recovery from severe, or prolonged, exercise is associated with the presence of lactic acid in the blood, as can be shown by direct analysis. The lactic acid produced by the muscles in moderate exercise is oxidized there in recovery before it can diffuse into the blood in appreciable amount. Consequently, recovery is rapid. In severe exercise, however, the lactic acid accumulates in the muscles to a high value, escaping thence into the blood and other tissues of the body, from which it can only slowly be removed, after diffusion back into the muscles, during the process of recovery.

Similar methods may be employed for measuring the maximum intake of oxygen, and recent experiments have shown that a man may use as much as 4.2 litres of oxygen per minute, after his circulation and respiration have been worked up by running fast for three or four minutes. This, you will remember, is about the amount which the body requires in recovery from 11 seconds of severe exertion. Were it not for the fact that the body is able, so to speak, to take its exercise on “credit”, instead of paying for it out of “income”, it would be impossible for a man to take anything but quite moderate exercise. The body is capable of running up an oxygen “debt” which must be repaid during the recovery process. The maximum “debt” which we have found is 15 litres, which is nearly four minutes supply at the maximum rate. We have little doubt that a first-class athlete, in the height of training, could run up a debt considerably greater than this. There is every reason to suppose that this process of “running into debt” for oxygen is associated with the accumulation of lactic acid in the muscle. Lactic acid is found in blood in comparatively large quantities after severe exercise: this acid must have come from the muscles. The respiratory quotient reaches values which are quite impossible on any supposition other than that the CO, is at first driven out from bicarbonate by lactic acid, and later restored to bicarbonate as the lactic acid is removed in recovery. This removal of lactic acid requires oxygen and corresponds to the recovery process which we have found in frog’s muscle. Experiments by my colleagues Long and Lupton have shown that the ratio of lactic acid removed to lactic acid oxidized is about the same as in isolated frog’s muscle, namely about 6 : 1.

This application to human muscular exercise is perhaps a digression, but I feel rather an interesting one. It shows that the purely academic study of the isolated frog’s muscle may be applied to the extremely important practical case of muscular exercise in man: it explains many of the well-known phenomena of athletics. We will return now to the frog and to the myo-thermic experiments made upon it.

If we take the case of the prolonged isometric contraction, heat is liberated in each of the three initial phases of contraction, maintenance, and relaxation. If the contraction be maintained for a long time, there is a steady heat production during the whole of that time, proportional to the tension developed. We may describe the phenomenon mathematically in the formula:

where H is total heat production, T is force developed, l is length of muscle, t is time during which the contraction is maintained, A and B are constants. It is found that A is independent of temperature, having, in the case of the sartorius muscle, always a value of about 1/6; B, which we may regard as the inverse of the “efficiency of maintaining a contraction”, depends on the type of muscle, on temperature, on fatigue, and on many other factors. If we take the important practical case of human movements, so much energy is required to set them up, so much to maintain them for a given time. The amount required to set up a given contraction is constant, the amount required to maintain it is variable, depending on the nature of the muscle and its condition at the time. Anything which slows the single twitch of a muscle makes summation more easy and B smaller: the muscle becomes more efficient for maintaining a contraction. The quickest muscles of all are the least efficient when it comes to exerting a force for a long time. There is an important effect of temperature on the rate at which the total heat production increases as the muscle continues to be tetanized – the rate of heat production is greater at the higher temperature. It would appear as though there were some ready store of energy which is, so to speak, exploded by the first few shocks, and that later a steady stream of energy must be maintained to keep up the contraction. Possibly Embden’s lactacidogen is the explosive substance used in the first few twitches of the summed contraction, the store which has been exploded being reformed continually by chemical reactions, from its precursor glycogen. If so, we should expect the rate at which restoration can go on to have a temperature coefficient of a chemical kind.

We have dealt so far, for several reasons, with the simple case of the isometric contraction : firstly, because it involves us in one less variable, namely, the length of the muscle, and secondly, because myothermic experiments on the isometric contraction are so much simpler and freer from error. Recent developments, however, of the technique have made it possible to study the heat production in a muscle which is allowed to shorten as much as one desires, and provided that stringent precautions be taken, reliable results are obtained. The temperature equilibrium in the muscle chamber must be so good that shortening over the junctions of the thermopile does not bring cooler or warmer parts of the muscle in contact with them. It must be remembered that this constancy of temperature must be to the nearest 1/100,000 of a degree because our scale of temperature is so small. During the last year Dr. W.O. Fenn has studied the effects of shortening and doing work upon the total liberation of energy by a muscle. He has found that when work is done, there is an “excess”. liberation of energy over and above that necessary in an isometric contraction of the same duration. The muscle is excited and allowed to shorten from one length to another, to lift various loads from one level to the other. The work done is proportional to the load, and the “excess” energy is also proportional to the load. If the load be held up at the end of the contraction so that the muscle relaxes unloaded, the excess energy is just about equal to the work done. If the muscle contracts freely and then lowers the load, excess energy is liberated of the same order of size as the work done by the load in falling: the muscle requires energy both to lower and to raise a weight. This is only one of the curious and unexpected results which Fenn has found. If a muscle be caused to lengthen during the development of its contraction, it gives out less energy than in an isometric twitch. If it be held fast and allowed to shorten only during relaxation, then again it will give out less heat. Shortening during contraction, lengthening during relaxation, appear to require excess liberation of energy. Lengthening during contraction, shortening during relaxation, appear to cause an excess “absorption” of energy, i.e. to lead to a total energy liberation less than that of the isometric twitch.

We are studying here the curious power which a muscle possesses of adapting its liberation of energy to the work it has to do. The subject is new and results are only now beginning to appear, but it is certain that we are dealing with a very fundamental property of the muscular machine. I should like shortly to illustrate the new principles which are emerging by some further examples.

Let us stimulate a muscle and allow its tension to develop isometrically until it has reached a maximum. Let us then, by a quick-release mechanism, allow the muscle to shorten suddenly and let us hinder its contraction by opposing it to the inertia of a mass; the mass employed may be either a fly-wheel, or an equilibrated beam, or a weight hanging on a long string and pulled horizontally. The greater the mass which opposes the contraction of the muscle, the more slowly will the muscle contract; the less the mass, the more rapidly will it contract. If a stimulated muscle were an elastic body, as Fick and others sometimes, as I always till recently, supposed, it would do the same work against a small mass as against a large one. It would turn the whole of the potential energy of strain which it possesses into kinetic energy in the mass. In muscle this is not so. The greater the speed of shortening, the less will be the work done. In the case of human-arm muscles the work does not attain anything near the maximum value unless the contraction has been opposed by a mass large enough to make it occupy at least two seconds. Even an unloaded contraction occupies about 0.25 seconds, in which case of course no work is done. Dependence of work on speed of movement I ascribed originally to the viscosity of the muscle substance: the greater the speed, the greater would be the fraction of the potential energy of the muscle which would be wasted in changing the muscle’s own form. The original experiments were made on man, and it was possible that the form of the curve was to be ascribed to the central nervous system, adjusting the innervation of the muscle to the work which it had to perform. This possibility is eliminated by the fact that the same identical phenomenon is found in the frog, as Gasser recently has shown. A frog’s muscle is stimulated and held fast, then suddenly released against the inertia of a mass. The kinetic energy produced is greater if the contraction be slow, and less if the contraction be fast, in a muscle subjected to a maximal tetanus. The phenomenon appears to be a genuine property of muscle. Gasser has found that the time relations of the frog’s muscle in this respect are totally different from those of man. Relatively speaking, the frog’s muscle is ten times quicker than that of man: it can do the same fraction of its maximum work when it contracts in about 1/10th of the time. This fact seems to indicate a curious and interesting application of the theory of dimensions, but I cannot discuss it further now. The difference in the time-scales of the two types of muscle makes one regard it as improbable that physical viscosity alone is the determining factor. One cannot see why viscosity should have ten times the effect in a human muscle than it has in a frog’s, and probably one hundred or one thousand times as much as it has in a fly’s. It would seem that we are dealing here with a fundamental mechanical property of a muscle which is actually shortening after stimulation.

Perhaps the facts we have just discussed are related to Fenn’s work, who found that the greater the work, the greater the excess heat. They suggest an adaptation of the chemical break-down of the muscle to the work performed. There may be some kind of positive physiological machinery in the muscle to regulate the speed of contraction to the requirements of the animal. I have no time now to go into the matter further, but I believe that we are beginning here to see a further striking adaptation of the body to its needs, of the muscle to its load. For those who like mechanical and electrical analogies I will refer to the case of the electric motor. If the motor be unloaded, a certain amount of energy is used: increase the load and the motor automatically takes more current: try to drive the motor from with-out and a back e.m.f. is produced, causing less current to be taken. It is clear, in any case, that the “all-or-none” principle is not completely applicable to the muscle fibre, if we state the principle in the form that the response depends only on the stimulus and on the initial circumstances. The amount of energy which the muscle gives out obviously depends on factors which come in only after the muscle has begun to shorten, on the inertia opposing its contraction, on the load it has to lift. State it in the form that the response cannot be varied by varying the stimulus and it still holds. It is clear also that those of us who supposed that a stimulated muscle is simply a new elastic body were wrong. A muscle may possess some elastic properties, but it requires more energy to do more work, a fact which is fundamentally in opposition to the elastic body theory.

There are many sides of this entrancing subject, on which I have no time to touch: there are many experiments which must still be done. We are dealing here with a genuine physical problem, involving statics, dynamics, thermodynamics, the design and employment of instruments: and it would seem that in the study of the mechanism of muscle we have a better opportunity of exploiting the use of these exact tools than perhaps on any other side of the investigation of living, working material. Our study, however, needs light also from another aspect, it requires the skilled labours of the organic and biochemists. We who have worked on the physical problems provided by the muscles could never have progressed, had Fletcher and Hopkins not put us on the trail: we should have been lost and bewildered had not Meyerhof, in the brilliant researches which he will now describe, ably led us through a part of the forest where our own methods are helpless. To take another analogy, the completion of the drawing will rest with the chemists: we physicists can only provide a sketch; we can indicate the type of machine and its properties, the chemists must describe it in detail.

*H also must be regarded as a function of the time.