The Mechanism of Life

We are indeed completely ignorant of the mode of trans- formation of chemical into kinetic energy in the living organism ; we know only that muscular contraction is accom- panied by a change of form ; at the moment of transformation the combustion of the muscle is increased, and during con- traction the stretched muscular fibre tends to acquire a spherical shape. It is this shortening of the muscular fibre which produces the mechanical movement. The step which we do not as yet fully understand is the physical phenomenon which intervenes between the disengagement of chemical energy and the occurrence of muscular contraction. Professor (TArsonval supposes that this missing step is a variation in the surface tension of the liquid in the muscular fibre. The surface tension of a liquid is due to the unbalanced forces of cohesion acting on the surface layer of molecules. Under the attraction of cohesion the molecules within the liquid are in a state of equilibrium, being equally attracted in all direc- tions, but those at the surface of the liquid are drawn towards the centre. The resultant of these attractive forces is a pressure normal to the surface, which is mechanically equiva- lent to an elastic tension tending to diminish the surface. In consequence of this surface tension the liquid has a tendency to assume the form in which its surface area is a minimum, i.e. the spherical form. If such a sphere is stretched into a cylinder or fibre by mechanical tension, it will shorten itself when released ; and if by any means we increase the surface tension of such a liquid fibre it will tend to assume a spherical form and contract just as a muscular fibre does. The surface tension of a liquid varies with its chemical composition ; the slightest chemical modification of a liquid alters the force of

this tension. We may therefore explain the mechanism of muscular contraction by supposing that a nervous impulse alters in some way the rate of combustion in a muscular fibre, that this alteration produces a momentary change in the chemical composition of the muscular cell, and that this change of chemical composition increases the surface tension of the cell sufficiently to provoke its contraction into a more spherical form. Ostwald has introduced a very useful conception for the study of this question of surface energy. A liquid surface contains a quantity of energy equal to its surface tension multiplied by its area, hence any variation either of area or of tension corresponds to a variation of its energy. This novel conception constitutes a valuable addition to the experimental study of the physiology of muscular action, since it gives us some idea of the mechanism by which chemical energy may be transformed into muscular contraction.

Whatever the mechanism of transformation in the animal machine, we have to consider the same quantities as in other motor machines. These are : (1) the efficiency ; (2) the potential energy ; (tf) the power ; (4) the energy given up to the medium under the form of heat ; (5) the temperature. Muscles, then, are merely transformers which change chemical energy into mechanical work, the diminution of stored-up energy in a muscle being expressed by the sensation of fatigue. A muscle may be studied in four different phases : (1) in repose ; () in a state of tension ; (3) when doing positive work ; (4) when work is being done on it.

When a muscle is in a state of tension, as when a weight is sustained by the outstretched arm, the muscle is producing no external work. The entire work done is converted into heat; just as it is in a dynamo or steam engine which is prevented from turning by a brake. Muscular contraction produces fatigue even when it does no external work. It is impossible for the muscle to support even the weight of the outstretched arm itself for any considerable time.

A muscle is doing positive work when it is raising a weight or moving a body from one point to another. The fourth state of muscular contraction is when th( muscle is doing negative work, i.e. when work is being done on it, as for instance when we go downstairs, or when a descending weight forces down the opposing arm which attempts to support it. In this case the muscles receive & portion of the energy lost by the descending weight, and thi? energy shows itself in the muscle in the form of heat. Trm increase of heat in a muscle doing negative work has been clearly demonstrated by the calorimetric experiments of Him and the thennometric experiments of Beclard. Hirifs ob- servations on muscular calorimetry show a production of heat corresponding to 150 calories per hour when in repose, 248 calories per hour during positive work, and 287 during negative work. BeclaixTs thennometric measurements alsc show that the temperature of a muscle rises each time that it contracts, and that the rise of temperature is greatest when the muscle is doing negative work, least during positive work, and intermediate when in a state of tension.

It is of the greatest importance in medical practice to distinguish between these different forms of muscular activity. There is a vast physiological difference between muscular contraction with the production of positive work, and muscular contraction without the production of work, or with negative work. To climb a flight of stairs is to contract the muscles with the production of work equal to the weight of the body multiplied by the height of the stairs. To descend the stairs is to contract the same muscles, but with the production oi negative work, and consequently a maximum of heat. To walk on level ground is to contract the muscles with the production of little or no external work ; as in a machine turning without friction in a vacuum.

We have seen that a fall of potential and a current of energy are the necessary conditions for the production of any natural phenomenon. Hence we may assume that the phenomenon of sensation is also accompanied by a fall of potential and a current of energy. When we touch a hot body, there is a flow of energy from the hot body to the hand. When we touch a cold body, there is a current of energy in the opposite direction. from the hand to the body. It was formerly held, and is still held by some physiologists, that the chief characteristic of life is the disproportion between an excitation and the response which it invokes from the organism. Such a doctrine can only be held by one who believes, at least implicitly, that the phenomena of life are supernatural, or at all events different in their nature from all other phenomena ; for the dispropor- tion between an excitation and the response it evokes is by no means confined to living things. This disproportion is universal in nature, and quite in conformity with the physical laws which govern the transformation of energy. The energy of living things is potential energy a fact which has been too little recognized. In the case of reflex actions it is self-evident, because the response is immediate, and always the same for the same stimulus. As in all other transformations, the stimulus consists in the intervention of a minimal quantity of external energy.

Long before the discovery of the laws of energy, Lamarck had recogni/ed and formulated this fact. He writes : " What would vegetable life be without excitations from without, what would be the life even of the lower animals without this cause?" In another passage, seeking for a power capable of exciting the action of the organism, he says : " The lower animal forms, without nervous system, live only by the aid of excitations which they receive from without. In the lowest forms of life this exciting force is borrowed directly from the environment, while in the higher forms the external exciting force is transferred to the interior of the living being and placed at the disposal of the individual."

This remark, that the movements of living things are not communicated but excited, that the external excitation only sets free latent or potential energy in the organism, shows that Lamarck had penetrated more deeply than many of the modern physiologists into the secrets of biological energy. We seek in vain in the text- books of physiology for any conception of potential energy in living beings, or the notion of an exciting force as the cause of sensation. All action of a living organism is reflex action. Every action has a cause, and

the cause of an organic action is an exciting energy from without, either immediate, or stored up in the nervous system from an external impression made at some previous epoch. Actions which are not evidently reHex are merely delayed reflexes; we have acquired the power of inhibiting, delaying, or modifying the response to an external stimulus, so that the same excitation may determine responses of very different kinds according to the mood produced by previous impressions. When carefully investigated, no action of ours is automatic ; every movement is determined by impressions derived from without. An action without a motive, that is without an external determining cause, would be an action without reason. In conclusion, we may formulate this general principle : The energy of a living being is potential energy ; sensations represent the intervention of an external exciting energy which provokes the response, i.e. the transformation of the potential energy already stored in the organism into the actual energy of motion and vital activity.

THE course of development of every branch of natural science has been the same. It begins by the observation and classifi- cation of the objects and phenomena of nature. The next step is to decompose the more complex phenomena in order to determine the physical mechanism underlying them the science has become analytical. Finally, when the mechanism of a phenomenon is understood, it becomes possible to repro- duce it, to repeat it by directing the physical forces which are its cause the science has now become synthetical.

Modern biology admits that the phenomena of life are physico-chemical in their nature. Although we have not as yet been able to define the exact nature of the physical and chemical processes which underlie all vital phenomena, yet every further discovery confirms our belief that the physical laws of life are identical with those of the mineral world, and modern research tends more and more to prove that life is produced by the same forces and is subject to the same laws that regulate inanimate matter.

The evolution of biology has been the same as that of the other sciences ; it has been successively descriptive, analytical, and synthetic. Just as synthetic chemistry began with the artificial formation of the simplest organic products, so bio- logical synthesis must content itself at first with the fabrication of forms resembling those of the lowest organisms. Like other sciences, synthetic biology must proceed from the simpler to the more complex, beginning with the reproduction of the more elementary vital phenomena. Later on we may hope to

unite and associate these, and to observe their development under various external influences. The synthesis of life, should it ever occur, will not be the sensational discovery which we usually associate with the idea. If we accept the theory of evolution, then the first dawn of the synthesis of life must consist in the production of forms inter- mediate between the inorganic and the organic world forms which possess only some of the rudimentary attributes of life, to which other attributes will be slowly added in the course of development by the evolutionary action of the environment.

Long ago, the penetrating genius of Lamarck seized on the idea that a knowledge of life could only be obtained by the comparison of organic with inorganic phenomena. He writes : " If we would acquire a real knowledge of what constitutes life, of what it consists, what are the causes and the laws which give rise to this wonderful phenomenon of nature, and how life can be the source of the multitude of forms presented to us by living organisms, we must before all consider with great attention the differences which exist between inorganic and living bodies ; and for this purpose we must compare side by side the essential characters of these two classes of bodies."

Synthetic biology includes morphogeny, physiogeny, and synthetic organic chemistry, which is also a branch of synthetic biology, since it deals with the composition of the constituents of living organisms. Synthetic organic chemistry is already a well-organized science, important by reason of the triumphs which it has already gained. The other two branches of biological synthesis, morphogeny, the synthesis of living forms and structures, and physiogeny, the synthesis of functions, can hardly as yet be said to exist as sciences. They are, however, no less legitimate and no less important than the sister science of synthetic chemistry.

Although morphogeny and physiogeny do not exist as well-organized and recognized sciences, there are already a number of works on the subject by enthusiastic pioneers independent seekers, who have not feared to abandon the 'paths of official science to wander in new and hitherto unexplored domains. The first experiment in physiogeny was the discovery of osmosis by the Abbe Nollet in 1748. He filled a pig's bladder with alcohol, and plunged it into water. He noticed that the bladder gradually increased in volume and became distended, the water penetrating into the interior of the bladder more quickly than the alcohol could escape. This was the first recorded experiment in the physics of nutrition and growth.

In 1866, Moritz Traube of Breslau discovered the osmotic properties of certain chemical precipitates. As I pointed out in the Revue Scientifique of March 1906, Traube made the first artificial cell, and studied the osmotic properties of membranes and their mode of production. This remarkable research should have been the starting - point of synthetic biology. The only result, however, was to give rise to numberless objections, and it soon fell into complete oblivion. " There are," says Traube, " a number of persons quite blind to all progress, who in the presence of a new discovery think only of the objections which may be brought against it." The works of Traube have been collected and published by his son (Gemmmelte Abhandlungen von Moritz Traube^

In 1867 there appeared in England a paper by Dr. E. Montgomery, of St. Thomas's Hospital, On the Formation of so-called Cells in Animal Bodies. This paper, published by Churchill & Sons, is a most interesting contribution and one of great originality. The author says : " There can be no compromise between the tenets of the cell theory and the conclusions arrived at in this paper ; the distinction is thorough. Either the units of which an organism is composed owe their origin to some kind or other of procreation, a mysterious act of that mysterious entity life, by which, in addition to their material properties, they become endowed with those peculiar metaphysical powers constituting vitality. Or, on the other hand, the organic units, like the crystalline units of inorganic bodies, form the organism by dint of similar inherent qualities, form in fact a living being possessed of all its inherent properties, as soon as certain chemical compounds are placed under certain physical conditions. If the former opinion be

true, then we must clearly understand that there exists naturally a break in the sequence of evolution, a chasm between the organic and the inorganic world never to be bridged over. If, on the contrary, the latter view be correct, then it strongly argues for a continuity of development, a gradual chemical elaboration, which culminates in those high compounds which, under surrounding influences, manifest those complex changes called vital. "Surely it is not a matter of indifference or of mere words, if the extreme aim of physiology avowedly be the detection ot the different functions dependent on the vital exertions of a variety of ultimate organisms, and the discovery of the specific stimulants which naturally incite these functions into play. Or, on the other hand, if it be understood to consist rather in the careful investigation of the succession of chemical differentiations and their accompanying physical changes, which give rise to the formation of a variety of tissues that are found to possess certain specific properties, to display certain definite actions due to a further flow of chemical and physical modifications. 1 '

In 1871 there appeared a memoir by the Dutch savant Harting entitled Recherche de Morphologic synthetique sur la production artificielk de quelqucs formations calcaires organiques. This memoir, says Professor R. Dubois, had cost Harting more than thirty years of work. " Synthetic morphology is yet only in its infancy, let us hope that in a time equal to that which has already expired since the first artificial production of urea, it will have made a progress equal to that of its older sister, synthetic chemistry."

In the Comptes Rendues of 1882 is the following note by D. Monnier and Karl Vogt : " 1. Figured forms presenting all the characteristics of organic growth, cells, porous canals, tubes with partition walls, and heterogeneous granules, may be produced artificially in appropriate liquids by the mutual action of two salts which form one or more insoluble salts by double decomposition. One of the component salts should be in solution, while the other salt must be introduced in the solid form.

44 52. Such forms of organic elements, cells, tubes, etc., may be produced either in an organic liquid or a semi-organic liquid such as sucrate of lime, or in an absolutely inorganic liquid such as silicate of soda. Thus there can no longer be any question of distinctive forms as characterizing organic bodies in contradistinction to inorganic bodies. "3. The figured elements of these pseudo-organic forms depend on the nature, the viscosity, and the concentration of the liquids in which they are produced. Certain viscous liquids such as solutions of gum arabic or chloride of zinc do not produce these forms.

" 4. The form of these artificial pseudo-organic products is constant, as constant as that of the crystalline forms of mineral salts. This form is so characteristic that it may often serve for the recognition of a minimal proportion of a substance in a mixture. The observation of these forms is a means of analysis as sensitive as that of the spectrum. We may, for example, differentiate in this way the alkaline bicarbonates from the sesqui-carbonates or the carbonates.

44 5. The form of these artificial pseudo-organic elements depends principally on the nature of the acid radical of the solid salt. Thus the sulphates and the phosphates generally produce tubes, while the carbonates form cells. 44 6. As a rule these pseudo-organic forms are engendered only by substances which are found in the living organism. Thus sucrate of calcium will engender organic forms, whereas sucrate of strontium or barium does not do so. There are, however, some exceptions to this rule, such as the sulphates of copper, cadmium, zinc, and nickel.

u 7. These artificial pseudo-organic elements are surrounded by veritable membranes, dializing membranes which allow only liquids to pass through them. These artificial cells have heterogeneous cell-contents, and produce in their interior granulations which are disposed in a regular order. Thus they are both in constitution and in form absolutely similar to the cellular elements which constitute living organisms. 44 8. It is probable that the inorganic elements which are present in the natural protoplasm may play an important part

in determining the form which is assumed by the figured elements of the organism." In 1902, Professor Quinke of Heidelberg, who has conse- crated his life with such distinction to the physics of liquids, writes thus of the organogenic power of liquids in a paper published in the Annalen der Physlk under the title " Unsichtbare Fliissigkeitschichtcn " : " In 1837, Gustav Rose obtained organic forms by precipitation from inorganic solutions. By precipitating chloride of calcium with the carbonates of ammonium and other alkaline carbonates, he obtained small spheres which grew and were transformed into calcic rhombohedra. He also obtained a flocculent precipitate which later became granular and showed under the microscope forms like the starfish, and discs with undulated borders. At Freiberg, in certain stalactites, Rose also discovered forms consisting of six pyramidal cells around a spherical nucleus.

"In 1889, Link obtained spherical granulations by the precipitation of calcic or plumbic solutions by potash, soda, or carbonic acid. These spherical granulations united after a time to form crystals. Sulphate of iron, ammoniated sulphate of zinc, sulphate of copper precipitated by sulphuretted hydrogen, and saline solutions precipitated by ferrocyanide of potash, all give granular precipitates or discs, of which the granular origin is quite perceptible.

"Runge in 1855 was the first to describe the formation of periodic chemical precipitates. He used blotting paper as the medium in which various chemical substances met by diffusion. In this way he studied the mutual reactions of solutions of ferrocyanide of potash, chloride of iron, and the sulphates of copper, iron, manganese, and zinc. The coloured precipitates appeared at different positions in the paper, and disappeared periodically at greater or longer intervals. The designs formed by these coloured precipitates change with the concentration of the saline solutions, or on the addition of oxalic acid, salts of potash or ammonia, and other substances. These designs are shown in a number of beautiful illustrations which accompany the work. In this

case the capillarity of the paper necessarily exerts a certain influence on the formation of the figures, but in addition to this, Runge admits the intervention of another force hitherto unknown, which he calls ' Bildungstrieb, 1 the formative impulse, which he considers to be the elementary vital force in the formation of plants and animals. " In 1867, R. Bottger obtained arborescent forms and ramifications of metallic vegetation by sowing fragments the size of a pea of crystals of the iron chlorides, chloride of cobalt, sulphate of manganese, nitrate and chloride of copper, etc., in an aqueous solution of silicate of sodium of specific gravity 1'18. These forms are due, as I shall show later on, to the surface tension of the oily precipitate ; Bottger gives no explanation of the phenomenon.