THE MECHANISM OF LIFE

THE

MECHANISM OF LIFE

BY

Dr. Stéphane LEDUC

PROFESSEUR À L'ÉCOLE DE MÉDECINE DE NANTES

TRANSLATED BY

W. DEANE BUTCHER

FORMERLY PRESIDENT OF THE RÖNTGEN SOCIETY, AND OF THE
ELECTRO-THERAPEUTICAL SECTION OF THE ROYAL SOCIETY OF MEDICINE

"La nature a formé, et forme tous

les jours les êtres les plus simples par

génération spontanée." Lamarck.

NEW YORK

R E B M A N C O M P A N Y

Herald Square Building
141-145, West 36th Street

First Impression March 1911

Second Impression January 1914

Printed in England

TRANSLATOR'S PREFACE

Professor Leduc's Théorie Physico-chimique de la Vie et Générations Spontanées has excited a good deal of attention, and not a little opposition, on the Continent. As recently as 1907 the Académie des Sciences excluded from its Comptes Rendus the report of these experimental researches on diffusion and osmosis, because it touched too closely on the burning question of spontaneous generation.

As the author points out, Lamarck's early evolutionary hypothesis was killed by opposition and neglect, and had to be reborn in England before it obtained universal acceptance as the Darwinian Theory. Not unnaturally, therefore, he turns for an appreciation of his work to the free air and wide horizon of the English-speaking countries.

He has entitled his book "The Mechanism of Life," since however little we may know of the origin of life, we may yet hope to get a glimpse of the machinery, and perhaps even hear the whirr of the wheels in Nature's workshop. The subject is of entrancing interest to the biologist and the physician, quite apart from its bearing on the question of spontaneous generation. Whatever view may be entertained by the different schools of thought as to the nature and significance of life, all alike will welcome this new and important contribution to our knowledge of the mechanism by which Nature constructs the bewildering variety of her forms.

There is, I think, no more wonderful and illuminating spectacle than that of an osmotic growth,—a crude lump of brute inanimate matter germinating before our very eyes, putting forth bud and stem and root and branch and leaf and fruit, with no stimulus from germ or seed, without even

the presence of organic matter. For these mineral growths are not mere crystallizations as many suppose; they increase by intussusception and not by accretion. They exhibit the phenomena of circulation and respiration, and a crude sort of reproduction by budding; they have a period of vigorous youthful growth, of old age, of death and of decay. They imitate the forms, the colour, the texture, and even the microscopical structure of organic growth so closely as to deceive the very elect. When we find, moreover, that the processes of nutrition are carried on in these osmotic productions just as in living beings, that an injury to an osmotic growth is repaired by the coagulation of its internal sap, and that it is able to perform periodic movements just as an animal or a plant, we are at a loss to define any line of separation between these mineral forms and those of organic life.

In the present volume the author has collected all the data necessary for a complete survey of the mechanism of life, which consists essentially of those phenomena which are exhibited at the contact of solutions of different degrees of concentration. Whatever may be the verdict as to the author's case for spontaneous generation, all will agree that the book is a most brilliant and stimulating study, founded on the personal investigation of a born experimenter.

The present volume is a translation of Dr. Leduc's French edition, but it is more than this, the work has been translated, revised and corrected, and in many places re-written, by the author's own hand. I am responsible only for the English form of the treatise, and can but regret that I have been able to reproduce so imperfectly the charm of the original.

W. DEANE BUTCHER.

Ealing.

PREFACE TO THE ENGLISH EDITION

C'est par l'initiative du Dr. Deane Butcher que cette ouvrage est presenté aux lecteurs anglais, à la race qui a doté l'humanité de tant de découvertes originales, geniales et d'une portée très générale.

Comme un être vivant, une idée exige pour naître et se développer le germe et le milieu de développement. Il est indéniable que le peuple anglo-américain constitue un milieu particulièrement favorable à la naissance et au développement des idées nouvelles.

Pendant notre collaboration le Dr. Deane Butcher a été un critique judicieux et éclairé, tous les changements dans l'édition anglaise sont dus à ses observations. Il s'est assimilé l'ouvrage pour le traduire, et dans beaucoup de parties, il a mis plus de clarté et de concision qu'il n'y en avait dans le texte original.

STÉPHANE LEDUC.

Nantes, 1911.

TABLE OF CONTENTS

INTRODUCTION

Life was formerly regarded as a phenomenon entirely separated from the other phenomena of Nature, and even up to the present time Science has proved wholly unable to give a definition of Life; evolution, nutrition, sensibility, growth, organization, none of these, not even the faculty of reproduction, is the exclusive appanage of life.

Living things are made of the same chemical elements as minerals; a living being is the arena of the same physical forces as those which affect the inorganic world.

Life is difficult to define because it differs from one living being to another; the life of a man is not that of a polyp or of a plant, and if we find it impossible to discover the line which separates life from the other phenomena of Nature, it is in fact because no such line of demarcation exists—the passage from animate to inanimate is gradual and insensible. The step between a stalagmite and a polyp is less than that between a polyp and a man, and even the trained biologist is often at a loss to determine whether a given borderland form is the result of life, or of the inanimate forces of the mineral world.

A living being is a transformer of matter and energy—both matter and energy being uncreateable and indestructible, i.e. invariable in quantity. A living being is only a current of matter and of energy, both of which change from moment to moment while passing through the organism.

That which constitutes a living being is its form; for a living thing is born, develops, and dies with the form and structure of its organism. This ephemeral nature of the living being, which perishes with the destruction of its form, is in

marked contrast to the perennial character of the matter and the energy which circulate within it.

The elementary phenomenon of life is the contact between an alimentary liquid and a cell. For the essential phenomenon of life is nutrition, and in order to be assimilated all the elements of an organism must be brought into a state of solution. Hence the study of life may be best begun by the study of those physico-chemical phenomena which result from the contact of two different liquids. Biology is thus but a branch of the physico-chemistry of liquids; it includes the study of electrolytic and colloidal solutions, and of the molecular forces brought into play by solution, osmosis, diffusion, cohesion, and crystallization.

In this volume I have endeavoured to give as much of the science of energetics as can be treated without the use of mathematical formulæ; the conception of entropy and Carnot's law of thermodynamics are also discussed.

The phenomena of catalysis and of diastatic fermentation have for the first time been brought under the general laws of energetics. This I have done by showing that catalysis is only one instance of the general law of the transformation of potential into kinetic energy, viz. by the intervention of a foreign exciting and stimulating energy which may be infinitely smaller than the energy it transforms. This conception brings life into line with other catalytic actions, and shows us a living being as a store of potential energy, to be set free by an external stimulus which may also excite sensation.

In a subsequent chapter I have dealt with the rise of Synthetic Biology, whose history and methods I have described. It is only of late that the progress of physico-chemical science has enabled us to enter into this field of research, the final one in the evolution of biological science.

The present work contains some of the earliest results of this synthetic biology. We shall see how it is possible by the mere diffusion of liquids to obtain forms which imitate with the greatest accuracy not only the ordinary cellular tissues, but the more complicated striated structures, such as muscle and mother-of-pearl. We shall also see how it is

possible by simple liquid diffusion to reproduce in ordered and regular succession complicated movements like those observed in the karyokinesis of the living cell.

The essential character of the living being is its Form. This is the only characteristic which it retains during the whole of its existence, with which it is born, which causes its development, and disappears with its death. The task of synthetic biology is the recognition of those physico-chemical forces and conditions which can produce forms and structures analogous to those of living beings. This is the subject of the chapter on Morphogenesis.

The last chapter deals with the doctrine of Evolution. The chain of life is of necessity a continuous one, from the mineral at one end to the most complicated organism at the other. We cannot allow that it is broken at any point, or that there is a link missing between animate and inanimate nature. Hence the theory of evolution necessarily admits the physico-chemical nature of life and the fact of spontaneous generation. Only thus can the evolutionary theory become a rational one, a stimulating and fertile inspirer of research. We seek for the physico-chemical forces which produce forms and structures analogous to those of living beings, and phenomena analogous to those of life. We study the alterations in environment which modify these forms, and we seek in the past history of our planet for those natural phenomena which have brought these physico-chemical forces into play. In this way we may find the road which will, we hope, lead some day to the discovery of the origin and the evolution of life upon the earth.

THE MECHANISM OF LIFE

CHAPTER I

LIFE AND LIVING BEINGS

Primitive man distinguished but two kinds of bodies in nature, those which were motionless and those which were animated. Movement was for him the expression of life. The stream, the wind, the waves, all were alive, and each was endowed with all the attributes of life—will, sentiment, and passion. Ancient Greek mythology is but the poetic expression of this primitive conception.

In the evolution of the intelligence, as in that of the body, the development of the individual is but a repetition of the development of the race. Even now children attribute life to everything that moves. For them a little bird still lives in the inside of a watch, and produces the tick-tick of the wheels. In modern times, however, we have learnt that everything in nature moves, so that motion of itself cannot be considered as the characteristic of life.

Heraclitus aptly compares life to a flame. Aristotle says, "Life is nutrition, growth, and decay,—having for its cause a principle which has its end in itself, namely ἐντελέχεια." This principle is itself in need of definition, and Aristotle only substitutes one unknown epithet for another.

Bichat defined life as the ensemble of the functions which resist death. This is to define life in terms of death,—but death is but the end of life, and cannot be defined without first defining life. Claude Bernard rejects all definition of life as insufficient, and incompatible with experimental science.

Some modern physiologists regard sensibility, others irritability, as the characteristic of life, and define life as the faculty of responding, by some sort of change, to an external stimulus. As in the case of movement, we have found by more attentive observation that this faculty also is universal in nature. There is no action without reaction; an elastic body repels the body that strikes it. Every object in nature dilates with heat, contracts with cold, and is modified by the light which it absorbs. Everything in nature responds to exterior action by a change, and hence this faculty cannot be the characteristic of life.

A distinguished professor of physiology was accustomed to teach that the disproportion between action and reaction was the characteristic of life. "Allow a gramme weight to fall on a nerve, and the muscle will raise a weight of ten grammes. This disproportion is the characteristic of life." But there is a much greater disproportion between action and reaction when the friction of a match blows up a powder factory, or the turning of a switch lights the lamps and animates the tramways and the motors of a great city. The disproportion between action and reaction is therefore no characteristic of life.

The essential characteristic of life is often said to be nutrition—the phenomenon by which a living organism absorbs matter from its environment, subjects it to chemical metamorphosis, assimilates it, and finally ejects the destructive products of metamorphosis into the surrounding medium. But this characteristic is also common to a great number of ordinary chemical reactions, so that we cannot call it peculiar to life. Consider, for instance, a fragment of calcium chloride immersed in a solution of sodium carbonate. It absorbs the carbonic ion, incorporates it into a molecule of calcium carbonate, and ejects the chlorine ion into the surrounding medium.

It may be argued that this is merely a chemical process, since the substance which determines the reaction is also modified, the chloride of calcium changing into carbonate of calcium. But every living thing is also changing its chemical

constitution during every moment of its existence,—it is this change which constitutes the process of senile involution. The substance of the child is other than that of the ovum, and the substance of the adult is not that of the child. Hence we cannot regard nutrition as the exclusive characteristic of life.

Other authorities regard growth and organization as the essentials of life. But crystals also grow. It was said that the growth of a crystal differed from that of a living thing, in that the former grew by the addition of material from without—the juxtaposition of bricks, as it were—while the latter grew by intussusception, an introduction of fresh material into the substance of the organism. A crystal, moreover, was homogeneous, while the tissues of a living being were differentiated—such differentiation constituting the organization. At the present time, however, we recognize the existence of a great variety of purely physical productions, the so-called "osmotic growths," which increase by a process of intussusception, and develop therefrom a marvellous complexity of organization and of form. Hence growth and organization cannot be considered as the essential characteristics of life.

Since, then, we are totally unable to define the exact boundary which separates life from the physical phenomena of nature, we may fairly conclude that no such separation exists. This is in conformity with the "law of continuity,"—the principle which asserts that all the phenomena of nature are continuous in time and space. Classes, divisions, and separations are all artificial, made not by nature but by man. All the forms and phenomena of nature are united by insensible transition; it is impossible to separate them, and in the distinction between living and non-living things we must content ourselves with relative definitions, which are far from being precise.

Life can only be defined as the sum of all phenomena exhibited by living beings, and its definition thus becomes a mere corollary to the definition of a living being.

The true definition of a living being is that it is a transformer of energy, receiving from its environment the energy

which it returns to that environment under another form. All living organisms are transformers of energy.

A living organism is also a transformer of matter. It absorbs matter from its environment, transforms it, and returns it to its environment in a different chemical condition. Living things are chemical transformers of matter.

Living beings are also transformers of form. They commence as a very simple form, which gradually develops and becomes more complicated.

The matter of which a living organism is constituted consists essentially of certain solutions of crystalloids and colloids. To this we may add an osmotic membrane to contain the liquids, and a solid skeleton to support and protect them. Finally, it would seem that a colloid of one of the albuminoid groups is a necessary constituent of every living being.

We may say, then, that a living being is a transformer of energy and of matter, containing certain albuminoid substances, with an evolutionary form, the constitution of which is essentially liquid.

A living being has but a limited duration. It is born, develops, becomes organized, declines and dies. Through all the metamorphoses of form, of substance, and of energy, informing the whole course of its existence, there is a certain co-ordination, a certain harmony, which is necessary for the conservation of the individual. This harmony we call Life. Discord is disease,—the total cessation of the harmony is Death. When the form is profoundly altered and the substance changed, the transformation of energy no longer follows its regular course, the organism is dead.

After death the colloids which have constituted the form of the living thing pass from their liquid state as "sols" into their coagulated state as "gels." The metamorphoses of form, substance, and energy still continue, but no longer harmoniously for the conservation of the individual, but in dis-harmony for its dissolution. Finally, the form of the individual disappears, the substance and the energy of the living being is resolved and dispersed into other bodies and other phenomena.

The results hitherto obtained from the study of life seem but inconsiderable when compared with the time and labour devoted to the question. Max Verworn exclaims, "Are we on a false track? Do we ask our questions of Nature amiss, or do we not read her answers aright?"

Each branch of science at its commencement employs only the simpler methods of observation. It is purely descriptive. The next step is to separate the different parts of the object studied—to dissect and to analyse. The science has now become analytical. The final stage is to reproduce the substances, the forms, and the phenomena which have been the subject of investigation. The science has at last become synthetical.

Up to the present time, biology has made use only of the first two methods, the descriptive and the analytical. The analytical method is at a grave disadvantage in all biological investigations, since it is impossible to separate and analyse the elementary phenomena of life. The function of an organ ceases when it is isolated from the organism of which it forms a part. This is the chief cause of our lack of progress in the analysis of life.

It is only recently that we have been able to apply the synthetic method to the study of the phenomena of life. Now that we know that a living organism is but the arena for the transformation of energy, we may hope to reproduce the elementary phenomena of life, by calling into play a similar transformation of energy in a suitable medium.

Organic chemistry has already obtained numerous victories in the same direction, and the rapid advance in the production of organic bodies by chemical synthesis may be considered the first-fruits of synthetic biology.

A phenomenon is determined by a number of circumstances which we call its causes, and of which it is the result. Every phenomenon, moreover, contributes to the production of other phenomena which are called its consequences. In order therefore to understand any phenomenon in its entirety, we must determine all its causes both qualitatively and quantitatively.

Phenomena succeed one another in time as consequences

one of another, and thus form an uninterrupted chain from the infinite of the past into the infinite of the future. A living being gathers from its entourage a supply of matter and of energy, which it transforms and returns. It is part and parcel of the medium in which it lives, which acts upon it, and upon which it acts. The living being and the medium in which it exists are mutually interdependent. This medium is in its turn dependent on its entourage,—and so on from medium to medium throughout the regions of infinite space.

One of the great laws of the universe is the law of continuity in time and space. We must not lose sight of this law when we attempt to follow the metamorphoses of matter, of energy and of form in living beings. Evolution is but the expression of this law of continuity, this succession of phenomena following one another like the links of a chain, without discontinuity through the vast extent of time and space.

The other great universal law, that of conservation, applies with equal force to living and to inanimate things. This law asserts the uncreateability and the indestructibility of matter and of energy. A given quantity of matter and of energy remains absolutely invariable through all the transformations through which it may pass.

We need not here discuss the question of the possible transformation of matter into ether, or of ether into ponderable matter. Such a transformation, if it exists, would have but little bearing on the phenomena of life. Moreover, it also will probably be found to conform to the law of conservation of energy.

In marked contrast to the permanence of matter and of energy is the ephemeral nature of form, as exhibited by living beings. Function, since it is but the resultant of form, is also ephemeral. All the faculties of life are bound up with its form,—a living being is born, exists, and dies with its form.

The phenomena of life may in certain cases slow down from their normal rapidity and intensity, as in hibernating

animals, or be entirely suspended, as in seeds. This state of suspension of life, of latent life as it were, reminds us of a machine that has been stopped, but which retains its form and substance unaltered, and may be started again whenever the obstacle to its progress is removed.

During the whole course of its life a living being is intimately dependent on its entourage. For example, the phenomena of life are circumscribed within very narrow limits of temperature. A living organism, consisting as it does essentially of liquid solutions, can only exist at temperatures at which such solutions remain liquid, i.e. between 0° C. and 100° C. Certain organisms, it is true, may be frozen, but their life remains in a state of suspension so long as their substance remains solid. Since the albuminoid substances which are a necessary component of the living organism become coagulated at 44° C., the manifestations of life diminish rapidly above this temperature. The intensity of life may be said to augment gradually as the temperature rises from 0° to 40°, and then to diminish rapidly as the temperature rises above that point, becoming nearly extinct at 60° C.

Another condition indispensable to life is the presence of oxygen. Life, compared by Heraclitus to a flame, is a combustion, an oxydation, for which the presence of oxygen at a certain pressure is indispensable. There are, it is true, certain anærobic micro-organisms which apparently exist without oxygen, but these in reality obtain their oxygen from the medium in which they grow.

Life is also influenced by light, by mechanical pressure, by the chemical composition of its entourage, and by other conditions which we do not as yet understand. In each case the conditions which are favourable or noxious vary with the nature of the organism, some living in air, some in fresh water, and others in the sea.

Formerly it was supposed that the substance of a living being was essentially different from that of the mineral world, so much so that two distinct chemistries were in existence—organic chemistry, the study of substances derived from bodies which had once possessed life, and inorganic chemistry, dealing

with minerals, metalloids, and metals. We now know that a living organism is composed of exactly the same elements as those which constitute the mineral world. These are carbon, oxygen, hydrogen, nitrogen, phosphorus, calcium, iron, sulphur, chlorine, sodium, potassium, and one or two other elements in smaller quantity. It was formerly supposed that the organic combinations of these elements were found only in living organisms and could be fashioned only by vital forces. In more recent times, however, an ever increasing number of organic substances have been produced in the laboratory.

Organic bodies may be divided into four principal groups. (1) Carbohydrates, including the sugars and the starches, all of which may be considered as formed of carbon and water. (2) Fats, which may be considered chemically as the ethers of glycerine, combinations of one molecule of glycerine and three molecules of a fatty acid, with elimination of water. (3) Albuminoids, substances whose molecules are complex, containing nitrogen and sulphur in addition to carbon, oxygen, and hydrogen. The albuminoid of the cell nucleus also contains phosphorus, and the hæmoglobin of the blood contains iron. (4) Minerals or inorganic elements, such as chloride of sodium, phosphate of calcium, and carbonic acid. This group also includes water, which is the most important constituent, since it forms more than a moiety of the substance of all living creatures.

Wöhler in 1828 accomplished the first synthesis of an organic substance, urea, one of the products of the decomposition of albumin. Since then a large number of organic substances have been prepared by the synthesis of their inorganic elements. The most recent advance in this direction is that of Emile Fischer, who has produced polypeptides having the same reactions as the peptones, by combining a number of molecules of the amides of the fatty acids.

In the further synthesis of organic compounds the problems we have before us are of the same order as those already solved. There is no essential difference between organic and inorganic chemistry; living organisms are formed of the

same elements as the mineral world, and the organic combinations of these elements may be realized in our laboratories, just as in the laboratory of the living organism.

Not only so, but a living being only borrows for a short time those mineral elements which, after having passed through the living organism, are returned once again to the mineral kingdom from which they came.

All matter has life in itself—or, at any rate, all matter susceptible of incorporation in a living cell. This life is potential while the element is in the mineral state, and actual while the element is passing through a living organism.

Mineral matter is changed into organic matter in its passage through a vegetable organism. The carbonic acid produced by combustion and respiration is absorbed by the chlorophyll of the leaves under the stimulus of light—the oxygen of the carbonic acid being returned to the air, while the carbon is utilized by the plant for the formation of sugar, starch, cellulose, and fats.

Thus plants are fed in great part by their leaves, taking an important part of their nourishment from the air, while by their roots they draw from the earth the water, the phosphates, the mineral salts, and the nitrates required for the formation of their albuminoid constituents. A vegetable is a laboratory in which is carried out the process of organic synthesis by which mineral materials are changed into organic matter. The first synthetic reaction is the formation of a molecule of formic aldehyde, CH₂O, by the combination of a molecule of water with an atom of carbon.

From this formic aldehyde, or formol, we may obtain all the various carbohydrates by simple polymerization, i.e. by the association of several molecules, with or without elimination of water. Thus two molecules of formol form one molecule of acetic acid, 2CH₂O = C₂H₄O₂. Three molecules of formol form a molecule of lactic acid, 3CH₂O = C₃H₆O₃. Six molecules of formol represent glucose and levulose, 6CH₂O = C₆H₁₂O₆. Twelve molecules of formol minus one molecule of water form saccharose, lactose, cane sugar, and sugar of milk, 12CH₂O = C₁₂H₂₂O₁₁ + H₂O; n times six

molecules of formol minus one molecule of water, n(C₆H₁₀O₅), form starch and cellulose.

Animals derive their nourishment from vegetables either directly, or indirectly through the flesh of herbivorous animals. The mineral matter, rendered organic in its passage through a vegetable growth, is finally returned by the agency of animal organisms to the mineral world again, in the form of carbonic acid, water, urea, and nitrates. Thus vegetables may be regarded as synthetic agents, and animals and microbes as agents of decomposition. Here also the difference is only relative, for in certain cases vegetables produce carbonic acid, while some animal organisms effect synthetic combinations. Moreover, there are intermediary forms, such as fungi, which possessing no chlorophyll are nourished like animals by organic matter, and yet like vegetables are able to manufacture organic matter from mineral salts.

The work of combustion begun by the animal organism is finished by the action of micro-organisms, who complete the oxydation—the re-mineralization of the chemical substances drawn originally from the inorganic world by the agency of plant life.

To sum up. Vegetables obtain their nourishment from mineral substances, which they reduce, de-oxydize, and charge with solar energy. Animal organisms on the contrary oxydize, and micro-organisms complete the oxydation of these substances, returning them to the mineral world as water, carbonates, nitrates, and sulphates.

Thus matter circulates eternally from the mineral to the vegetable, from the vegetable to the animal world, and back again. The matter which forms our structure, which is to-day part and parcel of ourselves, has formed the structure of an infinite number of living beings, and will continue to pursue its endless reincarnation after our decease.

This endless cycle of life is also an endless cycle of energy. The combination of carbon with water carried out by the agency of chlorophyll can only take place with absorption of energy. This energy comes directly from the sun, the red and orange light radiations being absorbed by the chlorophyll.

The arrest of vegetation during the winter months is due not so much to the lowering of temperature as to the diminution of the radiant energy received from the sun. In the same way shade is harmful to vegetation, since the radiant energy required for growth is prevented from reaching the plant.

The energy radiated by the sun is accumulated and stored in the plant tissues. Later on, animals feed on the plants and utilize this energy, excreting the products of decomposition, i.e. the constituents of their food minus the energy contained in it. Thus the whole of the energy which animates living beings, the whole of the energy which constitutes life, comes from the sun. To the sun also we owe all artificial heat, the energy stored up in wood and coal. We are all of us children of the sun.

The radiant energy of the sun is transformed by plants into chemical energy. It is this chemical energy which feeds the vital activity of animals, who return it to the external world under the form of heat, mechanical work, and muscular contraction, light in the glow-worm, electricity in the electric eel.

There is a marked difference between the forms affected by organic and inorganic substances. The forms of the mineral world are those of crystals—geometrical forms, bounded by straight lines, planes, and regular angles. Living organisms, on the contrary, affect forms which are less regular—curved surfaces and rounded angles. The physical reason for this difference in form lies in a difference of consistency, crystals being solid, whereas living organisms are liquids or semi-liquids. The liquids of nature, streams and clouds and dewdrops, affect the same rounded forms as those of living organisms.

Living beings for the most part present a remarkable degree of symmetry. Some, like radiolarians and star-fish, have a stellate form. In plants the various organs often radiate from an axis, in such a manner that on turning the plant about this axis the various forms are superposed thrice, four, or more often five times in one complete revolution. It is remarkable how often this number five recurs in the

divisions and parts of a living organism. In other cases the similar parts are disposed symmetrically on either side of a median line or plane, giving a series of homologous parts which are not superposable.

The most important characteristic of a living being is its form. This is implicitly admitted by naturalists, who classify animals and plants in genera and species according to the differences and analogies of their form.

All living beings are composed of elementary organizations called cells. In its complete state, a cell consists of a membrane or envelope containing a mass of protoplasm, in the centre of which is a nucleus of differentiated protoplasm. This nucleus may in its turn contain a nucleolus. In some cases the cell is merely a protoplasmic mass without a visible envelope, so that a cell may be defined as essentially a mass of protoplasm provided with a nucleus.

A living organism may consist merely of a single cell, which is able alone to accomplish all the functions of life. Most living beings, however, consist of a collection of innumerable cells forming a cellular association or community. When a number of cells are thus united to constitute a single living being, the various functions of life are divided among different cellular groups. Certain cells become specialized for the accomplishment of a single function, and to each function corresponds a different form of cell. It is thus easy to recognize by their form the nerve cells, the muscle cells which perform the function of movement, and the glandular cells which perform the function of secretion. The cells of a living being are microscopic in size, and it is remarkable that they never attain to any considerable dimensions.

In order that life may be maintained in a living organism, it is necessary that a continual supply of aliment should be brought to it, and that certain other substances, the waste-products of combustion, should be eliminated. In order to be absorbed and assimilated, the alimentary substances must be presented to the living organism in a liquid or gaseous state. Thus the essential condition necessary for the

maintenance of life is the contact of a living cell with a current of liquid. The elementary physical phenomenon of life is the contact of two different liquids. This is the necessary condition which renders possible the chemical exchanges and the transformations of energy which constitute life. It is in the study of the phenomena of liquid contact and diffusion that we may best hope to pierce the secrets of life. The physics of vital action are the physics of the phenomena which occur in liquids, and the study of the physics of a liquid must be the preface and the basis of all inquiry into the nature and origin of life.

CHAPTER II

SOLUTIONS

We have seen that living beings are transformers of energy and of matter, evolutionary in form and liquid in consistency; that they are solutions of colloids and crystalloids separated by osmotic membranes to form microscopic cells, or consisting merely of a gelatinous mass of protoplasm, with a nucleus of slightly differentiated material. The elementary phenomenon of life is the contact of two different solutions. This is the initial physical phenomenon from which proceed all the other phenomena of life in accordance with the ordinary chemical and physical laws. Thus the basis of biological science is the study of solution and of the phenomena which occur between two different solutions, either in immediate contact or when separated by a membrane.

A solution is a homogeneous mixture of one or more solutes in a liquid solvent. Before solution the solute or dissolved substance may be solid, liquid, or gaseous.

Solutes, or substances capable of solution, may be divided into two classes—substances which are capable of crystallization, or crystalloids; and those which are incapable of crystallization, the colloids. Crystalloids may be divided again into two classes, those whose solutions are ionizable and therefore conduct electricity, chiefly salts, acids, and bases; and those whose solutions are non-ionizable and are therefore non-conductors. These latter are for the most part crystallizable substances of organic origin, such as sugars, urea, etc.

Avogadro's law asserts that under similar conditions of temperature and pressure, equal volumes of various gases

contain an equal number of molecules. Under similar conditions, the molecular weights of different substances have therefore the same ratio as the weights of equal volumes of their vapours. Hence if we fix arbitrarily the molecular weight of any one substance, the molecular weight of all other substances is thereby determined. The molecular weight of hydrogen has been arbitrarily fixed as two, and hence the molecular weight of any substance will be double its gaseous density when compared with that of hydrogen.

Gramme-Molecule.—A gramme-molecule is the molecular weight of a body expressed in grammes. Occasionally for brevity a gramme-molecule is spoken of as a "molecule." Thus we may say that the molecular weight of oxygen is 16 grammes, meaning thereby that there are the same number of molecules in 16 grammes of oxygen as there are atoms in 1 gramme of hydrogen.

Concentration.—The concentration of a solution is the ratio between the quantity of the solute and the quantity of the solvent. The concentration of a solution is expressed in various ways. (a) The weight of solute dissolved in 100 grammes of the solvent. (b) The weight of solute present in 100 grammes of the solution. (c) The weight of solute dissolved in a litre of the solvent. (d) The weight of solute in a litre of the solution. The most usual method is to give the concentration as the weight of solute dissolved in 100 grammes or in one litre of the solvent.

Molecular Concentration.—Many of the physical and biological properties of a solution are proportional, not to its mass or weight concentration, but to its molecular concentration, i.e. to the number of gramme-molecules of the solute contained in a litre of the solution. Many physical properties are quite independent of the nature of the solute, depending only on its degree of molecular concentration.

Normal Solution.—A normal solution is one which contains one gramme-molecule of the solute per litre. A decinormal solution contains one-tenth of a gramme-molecule of the solute per litre, and a centinormal solution one-hundredth of a gramme-molecule. A normal solution of urea, for example,

contains 60 grammes of urea per litre, while a normal solution of sugar contains 342 grammes of sugar per litre.

The Dissolved Substance is a Gas.—Van t' Hoff, using the data obtained by the botanist Pfeffer, showed that the dissolved matter in a solution behaved exactly as if it were a gas. The analogy is complete in every respect. Like the gaseous molecules, the molecules of a solute are mobile with respect to one another. Like those of a gas, the molecules of a solute tend to spread themselves equally, and to fill the whole space at their disposal, i.e. the whole volume of the solution. The surface of the solution represents the vessel containing the gas, which confines it within definite limits and prevents further expansion.

Osmotic Pressure.—Like the molecules of a gas, the molecules of a solute exercise pressure on the boundaries of the space containing it. This osmotic pressure follows exactly the same laws as gaseous pressure. It has the same constants, and all the notions acquired by the study of gaseous pressure are applicable to osmotic pressure. Osmotic pressure is in fact the gaseous pressure of the molecules of the solute.

When a gas dilates and increases in volume, its temperature falls, and cold is produced. Similarly, when a soluble substance is dissolved, it increases in volume, and the temperature of the liquid falls. This phenomenon is well known as a means of producing cold by a refrigerating mixture.

The phenomena of life are governed by the laws of gaseous pressure, since all these phenomena take place in solutions. The fundamental laws of biology are those of the distribution of substances in solution, which is regulated by the laws of gaseous pressure, since all these laws are applicable also to osmotic pressure.

Boyle's Law.—When a gas is compressed its volume is diminished. If the pressure is doubled, the volume is reduced to one-half. The quantity V × P, that is the volume multiplied by the pressure, is constant.

Gay-Lussac's Law.—For a difference of temperature of a degree Centigrade all gases dilate or contract by 1 / 273 of their volume at 0° Centigrade.

Dalton's Law.—In a gaseous mixture, the total pressure is equal to the sum of the pressures which each gas would exert if it alone filled the whole of the receptacle.

Pressure proportional to Molecular Concentration.—The above laws are completely independent of the chemical nature of the gas, they depend only on the number of gaseous molecules in a given space, i.e. on the molecular concentration. If we double the mass of the gas in a given space, we double the number of molecules, and we also double the pressure, whatever the nature of the molecules. We may also double the pressure by compressing the molecules of a gas, or of several gases, into a space half the original size. The molecular concentration of a gas, or of a mixture of gases, is the ratio of the number of molecules to the volume they occupy. The pressure of a gas or of a mixture of gases is proportional to its molecular concentration. This is a better and a shorter way of expressing both Boyle's law and Dalton's law.

One gramme-molecule of a gas, whatever its nature, condensed into the volume of 1 litre, has a pressure of 22.35 atmospheres. Similarly one gramme-molecule of a solute, whatever its nature, when dissolved in a litre of water, has the same pressure, viz. 22.35 atmospheres.

Absolute Zero.—According to Gay-Lussac's law, the volume of a gas diminishes by 1 / 273 of its volume at 0° C. for each degree fall of temperature. Thus if the contraction is the same for all temperatures, the volume would be reduced to zero at -273° C. This is the absolute zero of temperature. Temperatures measured from this point are called absolute temperatures, and are designated by the symbol T. If t° indicates the Centigrade temperature above the freezing point of water, then the absolute temperature is equal to t° + 273°.

The Gaseous Constant.—Consider a mass of gas at 0° C. under a pressure P_o, with volume V_o. At the absolute temperature T, if the pressure be unaltered, the volume of this gas will be V_oT / 273. Therefore the constant PV, the product of the pressure by the volume, will be represented by P_oV_oT / 273.

At the same temperature, but under another pressure P′ the gas will have a different volume V′. Since, according to Boyle's law, PV is constant (P′V′ = P_oV_o), it will still equal P_oV_oT / 273. Therefore P_oV_o / 273 is also constant. This quantity is called "the gaseous constant," and if we represent it by the symbol R, we obtain the general formula PV = RT for all gases, or PV / T = R.

Suppose, for instance, we have a gramme-molecule of a gas at 0° C. in a space of 1 litre. It has a pressure of 22.35 atmospheres at 0° C., or 273° absolute temperature. Since PV = RT, R = PV / T = 1 × 22.35 / 273 = .0819. This number .0819 is the numerical value of the constant R for all gases, volume being measured in litres and pressure in atmospheres.

Substances in solution behave exactly like gases, they follow the same laws and have the same constants. All the conceptions which have been acquired by the study of gases are applicable to solutions, and therefore to the phenomena of life. The osmotic pressure of a solution is the force with which the molecules of the solute, like gaseous molecules, strive to diffuse into space, and press on the limits which confine them, the containing vessel being represented by the surfaces of the solution. Osmotic pressure is measured in exactly the same way as gaseous pressure. To measure steam pressure we insert a manometer in the walls of the boiler. In the same way we may use a manometer to measure osmotic pressure. We attach the tube to the walls of the porous vessel, allow the solvent to increase in volume under the pressure of the solute, and measure the rise of the liquid in the manometer tube.

Pfeffer's Apparatus.—Pfeffer has designed an apparatus for the measurement of osmotic pressure. It consists of a vessel of porous porcelain, the pores of which are filled with a colloidal solution of ferrocyanide of copper. This forms a semi-permeable membrane which permits the passage of water into the vessel, but prevents the passage of sugar or of any

colloid. The stopper which hermetically closes the vessel is pierced for the reception of a mercury manometer. The vessel is filled with a solution of sugar and plunged in a bath of water. The volume of the solution in the interior of the vessel can vary, since water passes easily in either direction through the pores of the vessel. The boundary of the solvent has become extensible, and its volume can increase or diminish in accordance with the osmotic pressure of the solute. Under the pressure of the sugar water is sucked into the vessel like air into a bellows, the solution passes into the tube of the manometer, and raises the column of mercury until its pressure balances the osmotic pressure of the sugar molecules.

Osmotic Pressure follows the Laws of Gaseous Pressure.—This osmotic pressure is in fact gaseous pressure, and may be measured in millimetres of mercury in just the same way. We may thus show that osmotic pressure follows the laws of gaseous pressure as defined by Boyle, Dalton, and Gay-Lussac. The coefficient of pressure variation for change of temperature is the same for a solute as for a gas. The formula PV = RT is applicable to both. The numerical value of the constant R is also the same for a solute as for a gas. being .0819 for one gramme-molecule of either, when the volume is expressed in litres and the pressure in atmospheres. The formula PV = RT shows that for a given mass, with the same volume, the pressure increases in proportion to the absolute temperature.

Osmotic Pressure of Sugar.—A normal solution of sugar, containing 342 grammes of sugar per litre, has a pressure of 22.35 atmospheres, and it may well be asked why such an enormous pressure is not more evident. The reason will be found in the immense frictional resistance to diffusion. Frictional resistance is proportional to the area of the surfaces in contact, and this area increases rapidly with each division of the substance. When a solute is resolved into its component molecules, its surface is enormously increased, and therefore the friction between the molecules of the solute and those of the solvent.

Isotonic Solutions.—Two solutions which have the same

osmotic pressure are said to be iso-osmotic or isotonic. When comparing two solutions of different concentration, the solution with the higher osmotic pressure is said to be hypertonic, and that with the lower osmotic pressure hypotonic.

Lowering of the Freezing Point.—Pure water freezes at 0° C. Raoult showed that the introduction of a non-ionizable substance, such as sugar or alcohol, lowers the freezing point of a solution in proportion to the molecular concentration of the solute. One gramme-molecule of the solute introduced into one litre of the solution lowers its temperature of congelation by 1.85° C. Thus a normal solution of any non-ionizable substance in water freezes at -1.85° C. The measurement of this lowering of the freezing point is called Cryoscopy, a method which is becoming of great utility in medicine.

Cryoscopy of Blood.—In order to determine the osmotic pressure of the blood at 37° C., i.e. 98.6° F., the normal temperature, we proceed as follows. On freezing the blood, we find that it congeals at -.56°. Its molecular concentration is therefore .56 / 1.85 = .30, or about one-third of a gramme-molecule per litre. Its osmotic pressure at 0° C. is therefore .3 × 22.35 = 6.7 atmospheres. The increase of pressure with temperature is the same as for a gas, viz. 1/273, or .00367 of its pressure at 0° for every degree rise of temperature. The increase of pressure at 37° is therefore .00367 × 37 × 6.7 = .9 atmospheres. The total osmotic pressure at 37° is therefore 6.7 + .9 = 7.6 atmospheres.

Rise of Boiling Point.—Water under atmospheric pressure boils at a temperature of 100° C. The addition of a solute whose solution does not conduct electricity, such as sugar, causes a rise in the boiling point proportional to the molecular concentration of that solute.

Lowering of the Vapour Tension.—The vapour tension of a liquid is lowered by the addition of a solute. A liquid boils at the temperature at which its vapour tension equals that of the atmosphere. Since an aqueous solution of sugar at atmospheric pressure does not begin to boil at 100° C., it is manifest that its vapour tension is then less than that of the

atmosphere. The addition of a solute such as sugar, whose solution is not ionizable, and therefore does not conduct electricity, lowers the vapour tension of the solution in proportion to the molecular concentration of the solute.

Corresponding Values.—We have thus found five properties of a solution which vary proportionally, so that from the measurement of any one of them we can determine the corresponding values of all the others. These are—

1. The Molecular Concentration.

2. The Osmotic Pressure.

3. The Diminution of Vapour Tension.

4. The Raising of the Boiling Point.

5. The Lowering of the Freezing Point.

Cryoscopy.—The usual method employed for the determination of the molecular concentration and osmotic pressure of a solution is by cryoscopy—the measurement of its temperature of congelation. A very sensitive thermometer is used, the scale of which extends over only 5° and is divided into hundredths of a degree. The liquid under examination is placed in a test tube, in which the bulb of the thermometer is plunged, and this is supported in a second tube with an air space all round it. The whole is then suspended to the under side of the cover of the refrigerating vessel, which may be cooled either by filling it with a freezing mixture, or by the evaporation of ether. During the whole of the operation the liquid is agitated by a mechanical stirrer. The first step is to determine the freezing point of distilled water. As the water cools the mercury gradually descends in the stem of the thermometer till it reaches a point below the zero mark at 0° C. As soon as ice begins to form the mercury rises, at first rapidly and then more slowly, reaches a maximum, and finally descends again. This maximum reading is the true point of congelation. The inner tube is then emptied, care being taken to leave a few small ice crystals to serve as centres of congelation for the subsequent experiment, thus avoiding supercooling of the solution. The process is then repeated with the solution under examination. The difference between

the two freezing points is the required "lowering of the freezing point."

Cryoscopy is the method most used in biological research to determine molecular concentration. It has, however, some grave defects. It necessitates several cubic centimetres of the liquid under examination. It gives us the constants of the solution at the temperature of freezing, which is far below that of life. Organic liquids are easily altered and are extremely sensible to minute differences of temperature, cryoscopy therefore gives us no information as to the constitution of solutions under normal conditions. It is desirable to have some other method of determining molecular concentration and the other interdependent constants at the normal temperature of life. A much better method, were it possible, would be the direct determination of the vapour tension of the solutions under normal conditions of temperature and pressure.

Molecular Lowering of the Freezing Point.—For every substance whose solution is not ionized and therefore does not conduct electricity, the lowering of the freezing point is the same, viz. 1.85° C. for each gramme-molecule of the solute per litre of the solution.

Determination of the Molecular Concentration.—In order to obtain the molecular concentration of a non-ionizable substance, we have only to determine the lowering of the freezing point. Let A be the lowering of the freezing point of any solution. On dividing it by 1.85 (the lowering of the freezing point for a normal solution), we obtain the number of gramme-molecules in a litre of the solution. If n be the number of gramme-molecules per litre, then n = A / 1.85.

Determination of the Osmotic Pressure.—The osmotic pressure P of a solution may be obtained by multiplying its molecular concentration n by 22.35 atmospheres. P = n × 22.35 = A / 1.85 × 22.35.

Determination of Molecular Weight.—The lowering of the freezing point also enables us to calculate the molecular

weight of any non-ionizable solute. Thus Bouchard has been able to determine by means of cryoscopy the mean molecular weight of the substances eliminated by the urine. A weight x of the substance is dissolved in a litre of water, and the lowering of the freezing point is observed. The value thus found divided by 1.85 gives us n, the number of gramme-molecules per litre. The molecular weight M may be determined by dividing the original weight x by n.

The study of osmotic pressure was begun by the Abbé Nollet; and one of his disciples, Parrot, at an early date thus described its importance: "It is a force analogous in all respects to the mechanical forces, a force able to set matter in motion, or to act as a static force in producing pressure. It is this force which causes the circulation of heterogeneous matter in the liquids which serve as its vehicle. It is this force which produces those actions which escape our notice by their minuteness and bewilder us by their results. It is for the infinitely small particles of matter what gravitation is for heavy masses. It can displace matter in solution upwards against gravity as easily as downwards or in a horizontal direction."

Thus the recognition of the fact that a substance in solution is really a gas, has at a single stroke put us in possession of the laws of osmotic pressure—laws slowly and laboriously discovered by the long series of investigations on the pressure of gases.

Osmotic pressure plays a most important rôle in the arena of life. It is found at work in all the phenomena of life. When osmotic pressure fails, life itself ceases.

CHAPTER III

ELECTROLYTIC SOLUTIONS

Solutions which conduct Electricity.—The laws of solution which we have studied in the previous chapter apply only to those solutions, chiefly of organic origin, which do not conduct electricity. Solutions of electrolytes such as the ordinary salts, acids, and bases, which are ionized on solution, give values for the various constants of solution which do not accord with those required by theory. If, for instance, we take a gramme-molecule of an electrolyte such as chloride of sodium, and dissolve it in a litre of water, we find that the lowering of the freezing point is nearly double the theoretical value of 1.85°. The same holds good for the osmotic pressure, and for all the constants which are proportional to the molecular concentration of the solute. The solution behaves, in each case, as if it contained more than one gramme-molecule of sodium chloride per litre. It behaves, in fact, as if it contained i times the number of molecules of solute originally introduced into it. If n be the original number of molecules, then it will apparently contain n′ = in molecules. This law is universal for all electrolytic solutions; the theoretical value for their concentration, osmotic pressure, and all the proportional physical constants must be multiplied by this quantity, i = n′/n, which is the ratio of the apparent number of the molecules present to the number originally introduced.

A similar dissociation of the molecule is observed in the case of many gases. The vapour of chloride of ammonium, for instance, is decomposed by heat, and it may be shown experimentally that the increase of pressure on heating above

that which theory demands, is due to an increase in the number of the gaseous molecules present. Some of the vapour particles are dissociated into two or more fragments, each of which plays the part of a single molecule.

Arrhenius, in 1885, advanced the hypothesis that the apparent increase in the number of molecules of an electrolytic solution was also due to dissociation. This interpretation at once threw a flood of light on a number of phenomena hitherto obscure.

Coefficient of Dissociation.—We have seen that in order to obtain values which accord with experiment we have to multiply the number of gramme-molecules of the solute by the coefficient i, which is called the Coefficient of Dissociation.

This coefficient of dissociation, i, may be found by observing the lowering of the freezing point of a normal solution, and dividing it by 1.85. i = t/1.85.

The coefficient of dissociation varies with the degree of concentration of the solution, rising to a maximum when the solution is sufficiently diluted.

If we know i, the coefficient of dissociation for a given solute, contained in a solution of a definite concentration, we can find n′, the number of particles present in a solution containing n gramme-molecules of the solute per litre, since n′ = in. On the other hand, if from a consideration of its freezing point and other constants we find that an electrolytic solution appears to contain n′ gramme-molecules per litre, the real number of chemical gramme-molecules in one litre of the solution will be only n′ / i = n.

Very concentrated solutions do not conform to these laws. In this they resemble gases, which as they approach their point of condensation tend less and less to conform to the laws of gaseous pressure.

Electrolysis.—If we take a solution of an acid, a salt, or a base, and dip into it two metallic rods, one connected to the positive and the other to the negative pole of a battery, we

find that the metals or metallic radicals of the solution are liberated at the negative pole, while the acid radicals of the salts and acids and the hydroxyl of the bases are liberated at the positive pole. The liberated substances may either be discharged unchanged, or they may enter into new combinations, causing a series of secondary reactions.

Electrolytes.—Solutions which conduct electricity are called Electrolytes, and the conducting metallic rods dipping into the solution are the Electrodes. Faraday gave the names of Ions to the atoms or atom-groups liberated at either electrode. The ions liberated at the positive electrode are the Anions, and those at the negative electrode are the Cations. The only solutions which possess any notable degree of electrical conductivity are the aqueous solutions of the various salts, acids, and bases, and in these solutions only do we meet with those phenomena of dissociation which are evidenced by anomalies of osmotic pressure, freezing point and the like,—anomalies which show that the solution contains a greater number of molecules than that indicated by its molecular concentration. These anomalies are due to dissociation, the division of some of the molecules into fragments, each of which plays the part of a separate molecule, contributing its quota to the osmotic tension and vapour pressure of the solution, in fact to all the phenomena which are dependent on the degree of molecular concentration. The electrical conductivity of a solution is therefore proved to be dependent on its molecular dissociation.

Arrhenius' Theory of Electrolysis.—In 1885, Arrhenius brought forward his theory of the transport of electricity by an electrolyte. According to this hypothesis, the electric current is carried by the ions, the positive charges by the cations, and the negative charges by the anions. In virtue of the attraction between charges of different sign, and repulsion between charges of like sign, the cations are repelled by the positive charge on the anode, and attracted by the negative charge on the cathode. Similarly the anions are repelled by the cathode and attracted by the anode.

An electrolytic solution contains three varieties of particles, positive ions or cations, negative ions or anions, and undissociated neutral molecules. The molecular concentration of such a solution, with the corresponding constants, depends on the total number of these particles, i.e. the sum of the ions and the undissociated neutral molecules. We may indicate an ion by placing above it the sign of its electrical charge, one sign for each valency. Thus Na⁺ and Cl^- indicate the two ions of a salt solution; Cu⁺⁺ and SO₄^-- the two ions of a solution of sulphate of copper. A point is sometimes substituted for the + sign, and a comma for the - sign. Thus Na^. and Cl^,; Cu^.. and SO₄^,,.

My friend Dr. Lewis Jones has given a very vivid picture of the processes which go on in an electrolytic solution when an electric current is passing. He compares an electrolytic cell to a ballroom, in which are gyrating a number of dancing couples, representing the neutral molecules, and a number of isolated ladies and gentlemen representing the anions and cations respectively. If we suppose a mirror at one end of the ballroom and a buffet at the other, the ladies will gradually accumulate around the mirror, and the gentlemen around the buffet. Moreover, the dancing couples will gradually be dissociated in order to follow this movement.

Degree of Dissociation.—The degree of dissociation is the fraction of the molecules in the solution which have undergone dissociation. Let n be the total number of molecules of the solute, and n″ the number of dissociated molecules. Then n″ / n = a will represent the degree of dissociation. Let k be the number of ions into which each molecule is split. Then a = n″k / nk, i.e. the degree of dissociation is the ratio of the number of ions actually present in a solution to the number which would be present if all the molecules of the solute were dissociated.

Let n′ be the total number of particles present in a solution

containing n molecules, each of which is composed of k ions. Then if a is the degree of dissociation,

n′ = n - an + ank,

n′ = n[1 + a (k - 1)],

n′ / n = 1 + a (k - 1) = i.

We thus obtain i the coefficient of dissociation, in terms of the degree of dissociation a and the number of ions in each molecule k.

If there is no dissociation, i.e. if a = 0, then n′ = n, and i = 1. If all the molecules are dissociated, a = 1, and i = k.

Faraday's Law.—Faraday found that the quantity of electricity required to liberate one gramme-molecule of any radical is 96.537 coulombs for each valency of the radical.

Electrochemical Equivalent.—The electrochemical equivalent of a radical is the weight liberated by one coulomb of electricity. It is equal to the molecular weight of the ion, divided by 96.537 times its valency.

Electrolytic Conductivity.—The conductivity of an electrolyte is the inverse of its resistance. C = 1/R.

For a given difference of potential the conductivity of an electrolyte is proportional to the number of ions in unit volume, the electrical charge on each ion, and the velocity of the ions.

The specific conductivity Δ of an electrolyte is the conductivity of a cube of the solution, each face of which is one square centimetre in area. The molecular conductivity of an electrolyte is the conductivity of a solution containing one gramme-molecule of the substance placed between two parallel conducting plates, one centimetre apart. The molecular conductivity is independent of the volume occupied by the gramme-molecule of the solute, depending only on the degree of dissociation. The molecular conductivity U is equal to the product of V, the volume of the molecule, by Δ, its specific conductivity. U = VΔ. Whence Δ = U / V, i.e. the specific

conductivity equals the molecular conductivity divided by the volume.

The conductivity of an electrolyte is proportional to the number of ions in a volume of the solution containing one gramme-molecule. Let M_∞ be the conductivity for complete dissociation and M_v the molecular conductivity at the volume V. Then

M_v / M_∞ = n″k / nk = n″ / n = a,

the degree of dissociation. This is Ostwald's law, which says that the degree of dissociation is equal to the ratio of conductivity when the gramme-molecule occupies a volume V, to its conductivity when the solution is so dilute that dissociation is complete. Hence the degree of dissociation may also be determined by comparing the electrical conductivities of two solutions of different degrees of concentration.

Velocity of the Ions.—If the electrolytic cell is divided into two segments by means of a porous diaphragm, we shall find after a time an unequal distribution of the solute on the two sides. For instance, with a solution of sulphate of copper, after the current has passed for some time there will be a diminution of concentration in the liquid on both sides of the diaphragm, but the loss will be very unequally divided. Two-thirds of the loss of concentration will be on the side of the negative electrode and only one-third on the positive side. In 1853, Hittorf gave the following ingenious explanation of this phenomenon:—

Fig. 1 represents an electrolytic vessel containing a solution of sulphate of copper, the vertical line indicating a porous partition separating the vessel into two parts. Fig. 2 shows the same vessel after the passage of the current. The acid radical has travelled twice as fast as the metal. For each copper ion which has passed through the porous plate towards the cathode two acid radicals have passed through it towards the anode. Three ions have been liberated at either electrode, but in consequence of the difference of velocity with which the positive and the negative ions have travelled, the negative side of the vessel contains only one molecule of copper sulphate and has lost two-thirds of its molecular concentration, while the positive side contains two molecules of copper sulphate and has only lost one-third of its concentration. This proves clearly that the ions move in different directions with different velocities. Let u be the velocity of the anions, and v the velocity of the cations. Let n be the loss of concentration at the cathode, and 1 - n the loss of concentration at the anode. Then

u / v = n / (1 - n),

i.e. the loss of concentration at the cathode is to the loss of concentration at the anode as the velocity of the anions is to that of the cations. Hence by measuring the loss of concentration at the two electrodes, we have an easy means of determining the comparative velocity of different ions.

In 1876, Kohlrausch compared the conductivity of the chlorides, bromides, and iodides of potassium, sodium, and ammonium respectively. He found that altering the cation did not affect the differences of conductivity between the three salts, thus showing that these differences of conductivity were dependent on the nature of the anion only, and not on the particular base with which it was combined. The difference of conductivity between an iodide and a bromide, for example, is the same whether potassium, sodium, or ammonium salts are compared. A similar experiment has been made with a series of cations combined with various anions. The difference of conductivity of the salts in the series is the same whichever anion is used, i.e. the difference of conductivity between potassium chloride and sodium chloride is the same as that between

potassium bromide and sodium bromide. Hence we may conclude that the conductivity of any salt is an ionic property.

Kohlrausch's law may be expressed by the formula c = d(u + v), where c is the conductivity of the salt, d the degree of dissociation, i.e. the fraction of the electrolyte broken up into ions, and u and v the velocity of the anions and cations respectively. When all the molecules of the electrolyte are dissociated, d = 1, and the formula becomes c_∞ = u + v.

As we have already seen, a salt is formed by the union of a metal M with an acid radical R. Potassium sulphate, K₂SO₄, consists of the metal K₂ and the acid radical SO₄. Ammonium chloride, NH₄Cl, consists of the basic radical NH₄ and the acid radical Cl. The various acids may be considered as salts of the metal hydrogen. Thus sulphuric acid, H₂SO₄, is the sulphate of hydrogen. Bases may be considered as salts with the hydroxyl group, OH, replacing the acid radical. Thus potash, KOH, is the hydroxyl of potassium. The various electrolytic combinations may be represented by the following symbols:—

Salts = MR.

Acids = HR.

Bases = MOH.

The various chemical reactions of an electrolyte are all ionic reactions, the chemical activity of an electrolytic solution being proportional to its electric conductivity, i.e. the degree of dissociation of its ions. The acidity of an electrolytic solution is due to the presence of the dissociated ion H⁺, and its strength is determined by the concentration of these free hydrogen ions. Hence the greater the degree of dissociation the stronger the acid.

The basic character of a solution is determined by the presence of the hydroxyl radical OH^-. The greater the concentration of the hydroxyl ions, i.e. the greater the dissociation, the stronger is the base.

The ions H⁺ and OH^- are of special importance, since they are the ions of water, H₂O = H⁺ + OH^-. The degree of

dissociation of pure water is but small. Water is, however, the most important of all the various agents in the chemical reactions of life, since a large number of organic substances are decomposed by water by a process of hydrolysis, and a vast number of organic substances are but combinations of carbon with the ions H⁺ and OH^-, their diversity being due to variations in the relative proportions and grouping.

The Chemical, Therapeutic, and Toxic Actions of Ions.—The chemical, therapeutic, antiseptic, and toxic actions of electrolytic solutions are almost exclusively due to ionization. Take, for instance, a solution of nitrate of silver in which the addition of chlorine produces a white precipitate of chloride of silver. This precipitate occurs only when the solution added is one such as NaCl, where the chlorine is present as the free ion Cl^-. No such precipitate is produced in a solution of chlorate of potassium or chloracetic acid, where the chlorine is entangled in the complex ion ClO₃ or C₂H₃ClO₂.

Since, then, the toxic and pharmacological properties of an electrolyte depend entirely on the ionic grouping, it behoves the physician and the biologist to study the structure and grouping of the ions in a molecule, rather than that of the atoms. Consider for a moment the totally different properties of the phosphides and the phosphates. The former are extremely toxic, while the latter are perfectly harmless. There is not the slightest analogy between their actions on the living organism. On the other hand, all the phosphides produce the same toxic and therapeutic effects, whatever the cation with which they are united. Their toxic properties are derived from the presence of the free phosphorus ion P^---. The phosphates contain phosphorus in the same proportion as the phosphides, but this phosphorus is harmlessly entangled in the complex ion PO₄^---, whose properties are absolutely different from those of the ion P^---.

The above considerations apply equally to the chlorides and chlorates, the iodides and iodates, the sulphides and sulphates, and in general to all chemical salts.

The question has an intimate bearing on practical pharmacology. When we prescribe a cacodylate or an amylarsinate, we are not prescribing an arsenical treatment whose effects can be compared with those of an arsenide, an arsenite, or an arsenate. This fact is sufficiently indicated by the difference in the toxic doses of the different salts. Each variety of arsenical ion has its own special physiological and therapeutic properties. We do not expect to obtain the results of a ferruginous treatment from the administration of a ferrocyanide or a ferricyanide. Both contain iron, it is true, but neither possess the properties of the cation Fe⁺⁺⁺, but rather those of the complex anion of which they form a part.

We have already said that most of the therapeutic, toxic, and caustic actions of an electrolyte are due to ionic action, and the substances can therefore have no toxic action unless they are dissociated. Many of the solvents employed in medicine, such as alcohol, glycerine, vaseline, and chloroform dissolve the electrolytes but do not dissociate them into ions, and these solutions therefore do not conduct electricity. Such solutions have no therapeutic action. With the absence of dissociation all the ionic toxic and caustic effects also disappear entirely, and only re-appear as the water of the tissue is able slowly to effect the necessary dissociation.

Carbolic acid dissolved in glycerine is hardly caustic and but very slightly toxic. We have met with several instances in which a tablespoonful of carbolized glycerine, in equal parts, has been swallowed without any ill effect, either caustic or toxic, whereas the same dose dissolved in water would have been fatal. This absence of dissociation has enabled the surgeon Mencière to inject carbolic and glycerine in equal proportions into the larger joints, the part being subsequently washed out with pure alcohol. Thus by employing vaseline, oil, or glycerine as a solvent, and avoiding the access of water, we are able to use electrolytic antiseptics in very concentrated form. Their action is brought out very slowly, as the water of the organism effects the necessary dissociation of the electrolyte.

Since all chemical, toxic, and therapeutic actions are ionic, they are proportional to the degree of ionic concentration, i.e. to the number of ions in a given volume. The only point of importance, that which determines their activity, whether chemical or therapeutic, is the degree of ionization or dissociation. For example, all acids have the same cation H⁺. They have all identical properties, but they differ widely in the intensity of their action. There are weak acids such as acetic acid, and strong acids like sulphuric acid. The stronger acids are those which are more thoroughly dissociated, and in which the ion H⁺ is very concentrated; whereas the feeble acids are but slightly dissociated, so that the ion H⁺ is less concentrated.

Paul and Krönig have shown that the bactericidal action of different salts also varies with their degree of dissociation, i.e. with the concentration of the active ions. They made a series of observations on the bactericidal action of various salts of mercury, the bichloride, the bibromide, and the bicyanide, on the spores of Bacillus anthracis. The following results were obtained from a comparison of solutions containing 1 gramme-molecule of the salt in 64 litres of water. With the bichloride solution, after exposure to the solution for twenty minutes, only 7 colonies of the bacillus were developed. After exposure to a similar solution of the bibromide the number of colonies was 34. The antiseptic action of the bichloride was therefore five times as great as that of the bibromide. The bicyanide of mercury, however, even when four times as concentrated, permitted the growth of an enormous number of colonies, showing that it had no appreciable antiseptic action whatever. Nevertheless, the proportion of Hg is the same in all the solutions, and if there were any difference one would naturally expect that the ion Cy^- would be more toxic than Cl^- or Br^-. The real condition which varies in these solutions and determines their activity is the degree of dissociation. The whole of the antiseptic property resides in the ion Hg⁺⁺. This ion is very

concentrated in the highly dissociated solution HgCl₂, less concentrated in the less ionized solution HgBr₂, and exceedingly dilute in the HgCy₂, which is hardly ionized at all.

What is true of the bactericidal action of the salts of mercury is equally true of their therapeutic effect. It is a great mistake to estimate the medicinal activity of a solution of a salt of mercury, or indeed of any electrolytic solution, simply by its degree of molecular concentration. The important point is the degree of dissociation, which is the only true measure of its activity. In the intramuscular injection of mercury salts it is by no means a matter of indifference what salt we employ. A salt should be used such as the bichloride or the biniodide, which is easily dissociated. Other salts are often employed because they occasion less pain at the site of injection; but the pain is a sign of the degree of activity of the preparation. The pain, it is true, may be avoided by using a salt which is less easily dissociated, or in which the mercury is bound up in a complex ion, but by so doing we diminish the efficacy of the remedy. It is moreover quite easy to diminish, or even entirely to suppress, the pain, by using a very dilute solution of an active ionized salt. A one-half per cent. or even one-quarter per cent. solution of the bichloride or biniodide of mercury may be injected very slowly in sufficient quantity without producing the slightest discomfort. Local action depends entirely on ionic concentration. One drop of pure sulphuric acid will destroy the skin, whereas the same amount if diluted in a tumblerful of water will furnish a refreshing drink.

CHAPTER IV

COLLOIDS

As we have already seen, living organisms are formed essentially of liquids. These liquids are solutions of crystallizable substances or crystalloids, and non-crystallizable substances or colloids—a classification which we owe to Graham.

The liquids are the most important constituents of a living organism, since they are the seat of all the chemical and physical phenomena of life. The junction of two liquids of different concentration is the arena in which takes place both the chemical transformation of matter and the correlative transformation of energy. In a former chapter we have passed in review the class of crystalloids, we will now turn our attention to the characteristic properties of colloids.

Colloids.—Colloids differ from crystalloids in that they do not form crystals from solution, being completely amorphous when in the solid state. The solution of a colloid solidifies in the same form which it possessed in the liquid state, the solvent being enclosed in the meshes of a sort of network formed by the solute. This form is approximately retained even after the water has evaporated by drying, the passage from the liquid state of solution to the solid state being effected through a series of intermediary states, such as a clot, coagulum, or jelly. This passage from the state of solution into a state of jelly is called coagulation. Some colloids, such as gelatine, coagulate with cold; while others, such as egg-albumin, coagulate with heat. Some, like the caseine of milk, require the addition of certain chemical substances to set up coagulation; while still others, such as the fibrin of blood, appear to coagulate spontaneously. The physical phenomena of

coagulation are still but little understood. In some cases it is a reversible phenomenon, thus gelatine coagulated by cold is redissolved by heat; whereas with other colloids the process is irreversible, albumin coagulated by heat is not redissolved on cooling.

Colloids in a state of coagulation have a vacuolar or sponge-like structure. The solvent is imprisoned in the vacuoles of the clot, and is expelled little by little by its retraction. Colloids diffused in water are usually called colloidal solutions, but they are not true solutions. Such a pseudo-solution of a colloid is called a "sol," while a colloid in a state of coagulation is called a "gel." Colloidal solutions spread but little, diffuse very slowly in the liquids of the body, and cannot penetrate organic membranes.

Colloidal solutions diffuse light, unlike crystalloid solutions, which are transparent. We all know how the trajectory of a beam of sunlight through a darkened room is rendered visible by the particles of dust. In the same way if a colloidal solution is illuminated by a transverse ray of light, the light is diffused by the molecules of the colloid in semi-solution, and the liquid appears faintly illuminated on a dark background. The light diffused by a colloidal solution is polarized, which shows that it is reflected light,

Siedentopf and Sigmondy have applied this principle of lateral illumination on a dark background to the construction of the ultra-microscope. With the aid of this instrument we may not only see, but count the particles in a colloidal solution, which is in reality merely a pseudo-solution or suspension, in contradistinction to the true solution of a crystalloid.

Colloidal solutions possess only a very feeble osmotic pressure. The lowering of the freezing point and the other corresponding constants are also quite insignificant. This arises from the fact that the molecules of a colloid are extremely large when compared with those of a crystalloid. For example let us take colloidal substance whose molecular weight is 2000. A solution containing 40 grammes per litre would have an osmotic pressure only one-fiftieth of that of a

solution of similar strength of a crystalloid whose molecular weight was 40.

Not only so, but on measuring the molecular concentration, the osmotic pressure, and the other constants of a colloidal solution, we find values even lower than those which we should expect from a consideration of its molecular weight. This is probably due to the tendency of a colloid to polymerization, i.e. to form groups or associations of molecules. Suppose, for instance, that the molecules of a colloidal solution are aggregated into groups of ten. Since each group plays the part of a simple molecule, the osmotic pressure will be ten times less than that corresponding to the quantity of the solute present. Such a group of molecules is called by Naegeli a "micella."

Similar phenomena of aggregation may be observed in the molecules of many inorganic substances. The molecule of iodine, for example, is monatomic at 1200° C., but becomes diatomic at the ordinary temperature. Sulphur at 860° C. is a gas with a vapour density of 2.2, while at 500° C. its vapour density rises to 6.6. In both of these cases two or more molecules of the element have been condensed into one as a result of the fall of temperature.

We frequently find that two successive cryoscopic observations on the freezing point of the same colloidal solution will vary. This is due to the extreme sensitiveness of the micellæ, which absorb or abandon their extra molecules under the slightest influence. This mobility in the constitution of the micellæ appears to be one of the principal causes of the peculiar properties of colloidal solutions.

The phenomenon of polymerization appears to be reversible. The micellæ are formed under certain conditions, and are disintegrated when these conditions are removed. The osmotic pressure varies in the same manner, diminishing with polymerization and augmenting with the disintegration of the micellæ. One may easily understand what an important rôle is played by this alternate polymerization and disintegration in the phenomena of life.

Most colloidal substances are precipitated from their solutions by the addition of very small quantities of electrolytic

solutions. Non-electrolytic solutions do not appear to provoke this precipitation. This is not a chemical action, for an exceedingly small quantity of an electrolyte is able to precipitate an indefinite quantity of the colloid. The precipitation is probably due to the electric charges carried by the dissociated ions of the electrolytes.

When an electric current is passed through a colloid solution, the course of the molecules of the colloid is sometimes towards the cathode and sometimes towards the anode, according to the nature of the colloid and of the solvent. This displacement would appear to indicate a difference of electric potential between the molecules of the colloid and those of the solvent. Hardy has shown that in an alkaline solution the molecules of albumin travel towards the anode, while in an acid solution they travel towards the cathode.

Metallic Colloids.—Carey Lea and afterwards Credé succeeded in obtaining silver in colloidal solution by ordinary chemical means. Professor Bredig has introduced a more general method of obtaining a number of metals in colloidal solutions in a state of great purity. He causes an electric arc to pass between two rods of the metal immersed in distilled water. The cathode is thus pulverized into a very fine powder which rests in suspension in the liquid, constituting a colloidal solution. Bredig has in this way prepared sols of platinum, palladium, iridium, silver, and cadmium.

Catalytic Properties of Colloids.—Catalysis is the property possessed by certain bodies of initiating chemical reaction. The mass of the catalyzing body has no definite proportion to that of the substances entering into the reaction, and the appearance of the catalyzer is in no way altered by the reaction.

Ostwald has shown that catalysis consists essentially in the acceleration or retardation of chemical reactions which would take place without the action of the catalyzer, but more slowly.

Catalytic reactions are very numerous in chemistry. The inversion of sugar by acids, the etherization of alcohol by sulphuric acid, the decomposition of hydrogen peroxide by

platinum black are all instances of catalysis. Fermentation by means of a soluble ferment or diastase, a phenomenon which may almost be called vital, is also a catalytic action. The action of pepsin, of the pancreatic ferment, of zymase, and of other similar ferments has a great analogy with the purely physical phenomenon of catalysis. The diastases are all colloids, and so are many other catalyzers.

A catalyzer is a stimulus which excites a transformation of energy. The catalyzer plays the same rôle in a chemical transformation as does the minimal exciting force which sets free the accumulation of potential energy previous to its transformation into kinetic energy. A catalyzer is the friction of the match which sets free the chemical energy of the powder magazine.

Bredig has studied the catalytic decomposition of hydrogen peroxide by metallic colloids prepared by his electric method. He found that 1 atom-gramme of colloidal platinum gives a sensible catalytic effect when diluted with 70 million litres of water. Caustic soda and other chemical substances inhibit the catalytic action of colloidal platinum in the same way as they inhibit the fermenting action of diastase. The curve of decomposition of hydrogen peroxide by colloidal platinum may be compared with the curve of fermentation by emulsin. Both are equally affected by the addition of an alkali. Many other chemical and physical agents have a similar inhibitory action on the catalysis of colloidal metals and on diastasic fermentation. Thus a mere trace of sulphuretted hydrogen or hydrocyanic acid will paralyse the action of a colloidal metal, just as it does that of a ferment. This is what Bredig calls the poisoning of metallic ferments.

We may hope that the further study of catalysis, a purely physico-chemical phenomenon, may throw more light on the mechanism of diastasic fermentation, which is essentially a vital reaction.

It must not be forgotten that all classification is artificial and arbitrary, and only to be used as long as it facilitates study. This observation is particularly applicable to the classification of substances into crystalloids and colloids.

There is no sharp line between the two groups, the passage is gradual, and it is impossible to say where one group ends and the other begins. Many colloids such as hæmoglobin are crystallizable, and many crystallizable substances are coagulable. Many substances appear at one time in the crystalloid state and at another time in the colloidal state, so that instead of dividing substances into colloids and crystalloids, we should rather consider these expressions as denoting different phases assumed by the same substance.

In order to define clearly our various classes and divisions, we are apt to exaggerate slight differences of properties or composition. We say that colloids have no osmotic pressure, whereas in fact the osmotic pressure of the colloids though feeble plays a very important part in the phenomena of life.

So in other departments of science—a factor which is almost infinitesimal may yet exercise a vast influence on the results. It is by infinitesimal variations of pressure, a thousandth of a millimetre or less, that we obtain the various degrees of penetration in the Röntgen rays.

The division into solutions and pseudo-solutions or suspensions is also an arbitrary one. A true solution is also a suspension of the molecules of the solute. There is no essential difference between a solution and a suspension, but only a difference in the size of the molecules, or agglomerations of molecules, in one case so small as to be transparent, and in the other case just big enough to diffuse light. There are moreover many properties common to colloidal solutions and suspensions of fine powders, such as kaolin, mastic, charcoal, or Indian ink. These particles in suspension are precipitated by solutions of electrolytes in a manner similar to the coagulation of colloids.

The surface of every liquid is covered by a very thin layer, a sort of membrane slightly differentiated from the rest of the liquid. This membrane may be a chemical one, a pellicular precipitate like that which is formed by the contact of two membranogenous liquids. On the other hand, the membrane may not differ from the subjacent liquid in chemical composition, but only in physical properties. If we

consider the molecules in the middle of a liquid, each molecule is subjected to the cohesive attraction of molecules on every side, attractions which neutralize one another. At the surface of the liquid, however, there are quite other conditions of equilibrium. There each molecule is drawn downwards towards the centre of the liquid, and there is no compensating attraction in an opposite direction. The resultant pressure is normal to the surface of the liquid, and is mechanically equivalent to an elastic membrane which tends to diminish the surface, and hence the volume of the liquid. We may therefore regard this surface tension as acting the part of a veritable physical membrane.

There is a still further differentiation of the surface of a liquid. When the liquid is not a simple one, but complex as in a solution, we find that the concentration of the solute is greater at the surface than in the interior. This is the so-called phenomenon of "adsorption," which is another cause for the production of a physical membrane covering the surface of a liquid.

Substances in a colloidal state have a great tendency to form these chemical or physical membranes at the point of contact between the colloidal solute and the solvent. This is probably the reason why the coagulum of a colloidal liquid usually presents a vacuolar or spongy structure.

CHAPTER V

DIFFUSION AND OSMOSIS