The Project Gutenberg eBook, The Organism as a Whole, by Jacques Loeb

“He was one of those simple, disinterested, and intellectually sterling workers to whom their own personality is as nothing in the presence of the vast subjects that engage the thoughts of their lives.”
John Morley.
(Article Diderot, Encyclopædia Britannica.)

PREFACE

It is generally admitted that the individual physio­logical processes, such as diges­tion, metabolism, the produc­tion of heat or of electricity, are of a purely physico­chemical character; and it is also conceded that the func­tions of individual organs, such as the eye or the ear, are to be analysed from the viewpoint of the physicist. When, however, the biologist is confronted with the fact that in the organism the parts are so adapted to each other as to give rise to a harmonious whole; and that the organisms are endowed with structures and instincts calculated to prolong their life and perpetuate their race, doubts as to the adequacy of a purely physico­chemical viewpoint in biology may arise. The difficulties besetting the biologist in this problem have been rather increased than diminished by the discovery of Mendelian heredity, according to which each character is transmitted independently of any other character. Since the number of Mendelian characters in each organism is large, the possibility must be faced that the organism is merely a mosaic of independent hereditary characters. If this be the case the ques­tion arises: What moulds these independent characters into a harmonious whole?

The vitalist settles this ques­tion by assuming the existence of a pre-established design for each organism and of a guiding “force” or “principle” which directs the working out of this design. Such assump­tions remove the problem of accounting for the harmonious character of the organism from the field of physics or chemistry. The theory of natural selec­tion invokes neither design nor purpose, but it is incomplete since it disregards the physico­chemical constitu­tion of living matter about which little was known until recently.

In this book an attempt is made to show that the unity of the organism is due to the fact that the egg (or rather its cytoplasm) is the future embryo upon which the Mendelian factors in the chromo­somes can impress only individual characteristics, probably by giving rise to special hormones and enzymes. We can cause an egg to develop into an organism without a spermato­zoön, but apparently we cannot make a spermato­zoön develop into an organism without the cytoplasm of an egg, although sperm and egg nucleus transmit equally the Mendelian characters. The concep­tion that the cytoplasm of the egg is already the embryo in the rough may be of importance also for the problem of evolu­tion since it suggests the possibility that the genus- and species-heredity are determined by the cytoplasm of the egg, while the Mendelian hereditary characters cannot contribute at all or only to a limited extent to the forma­tion of new species. Such an idea is supported by the work on immunity, which shows that genus- and probably species-specificity are due to specific proteins, while the Mendelian characters may be determined by hormones which need neither be proteins nor specific or by enzymes which also need not be specific for the species or genus. Such a concep­tion would remove the difficulties which the work on Mendelian heredity has seemingly created not only for the problem of evolu­tion but also for the problem of the harmonious character of the organism as a whole.

Since the book is intended as a companion volume to the writer’s former treatise on The Comparative Physiology of the Brain a discussion of the func­tions of the central nervous system is omitted.

Completeness in regard to quota­tion of literature was out of the ques­tion, but the writer notices with regret, that he has failed to refer in the text to so important a contribu­tion to the subject as Sir E. A. Schäfer’s masterly presidential address on “Life” or the addresses of Correns and Goldschmidt on the determina­tion of sex. Credit should also have been given to Professor Raymond Pearl for the discrimina­tion between species and individual inheritance.

The writer wishes to acknowledge his indebtedness to his friends Professor E. G. Conklin of Princeton, Professor Richard Goldschmidt of the Kaiser Wilhelm Institut of Berlin, Dr. P. A. Levene of the Rockefeller Institute, Professor T. H. Morgan of Columbia University, and Professor Hardolph Wasteneys of the University of California who kindly read one or more chapters of the book and offered valuable sugges­tions; and he wishes especially to thank his wife for suggesting many correc­tions in the manuscript and the proof.

The book is dedicated to that group of freethinkers, including d’Alembert, Diderot, Holbach, and Voltaire, who first dared to follow the consequences of a mechanistic science—incomplete as it then was—to the rules of human conduct and who thereby laid the founda­tion of that spirit of tolerance, justice, and gentleness which was the hope of our civiliza­tion until it was buried under the wave of homicidal emo­tion which has swept through the world. Diderot was singled out, since to him the words of Lord Morley are devoted, which, however, are more or less characteristic of the whole group.

J. L.

The Rockefeller Institute
for Medical Research,
August, 1916

CONTENTS

The Organism as a Whole

CHAPTER I

INTRODUCTORY REMARKS

1. The physical researches of the last ten years have put the atomistic theory of matter and electricity on a definite and in all probability permanent basis. We know the exact number of molecules in a given mass of any substance whose molecular weight is known to us, and we know the exact charge of a single electron. This permits us to state as the ultimate aim of the physical sciences the visualiza­tion of all phenomena in terms of groupings and displacements of ultimate particles, and since there is no discontinuity between the matter constituting the living and non-living world the goal of biology can be expressed in the same way.

This idea has more or less consciously prevailed for some time in the explana­tion of the single processes occurring in the animal body or in the explana­tion of the func­tions of the individual organs. Nobody, not even a scientific vitalist, would think of treating the process of diges­tion, metabolism, produc­tion of heat, and electricity or even secre­tion or muscular contrac­tion in any other than a purely chemical or physico­chemical way; nor would anybody think of explaining the func­tions of the eye or the ear from any other standpoint than that of physics.

When the actions of the organism as a whole are concerned, we find a totally different situa­tion. The same physiologists who in the explana­tion of the individual processes would follow the strictly physico­chemical viewpoint and method would consider the reac­tions of the organism as a whole as the expression of non-physical agencies. Thus Claude Bernard,1 who in the investiga­tion of the individual life processes was a strict mechanist, declares that the making of a harmonious organism from the egg cannot be explained on a mechanistic basis but only on the assump­tion of a “directive force.” Bernard assumes, as Bichat and others had done before him, that there are two opposite processes going on in the living organism: (1) the phenomena of vital crea­tion or organizing synthesis; (2) the phenomena of death or organic destruc­tion. It is only the destructive processes which give rise to the physical manifesta­tions by which we judge life, such as respira­tion and circula­tion or the activity of glands, and so on. The work of crea­tion takes place unseen by us in the egg when the embryo or organism is formed. This vital crea­tion occurs always according to a definite plan, and in the opinion of Bernard it is impossible to account for this plan on a purely physico­chemical basis.

In other words, Bernard thinks it his task to account for individual life phenomena on a purely physico­chemical basis—but the harmonious character of the organism as a whole is in his opinion not produced by the same forces and he considers it impossible and hopeless to investigate the “design.” This attitude of Bernard would be incomprehensible were it not for the fact that, when he made these statements, the phenomena of specificity, the physi­ology of development and regenera­tion, the Mendelian laws of heredity, the animal tropisms and their bearing on the theory of adapta­tion were unknown.

This explanation of Bernard’s attitude is apparently contradicted by the fact that Driesch2 and v. Uexküll,3 both brilliant biologists, occupy today a standpoint not very different from that of Claude Bernard. Driesch assumes that there is an Aristotelian “entelechy” acting as directing guide in each organism; and v. Uexküll suggests a kind of Platonic “idea” as a peculiar characteristic of life which accounts for the purposeful character of the organism.

v. Uexküll supposes as did Claude Bernard and as does Driesch that in an organism or an egg the ultimate processes are purely physico­chemical. In an egg these processes are guided into definite parts of the future embryo by the Mendelian factors of heredity—the so-called genes. These genes he compares to the foremen for the different types of work to be done in a building. But there must be something that makes of the work of the single genes a harmonious whole, and for this purpose he assumes the existence of “supergenes.”4 v. Uexküll’s ideas concerning the nature of a Mendelian factor and of the “supergenes” are expressed in metaphorical terms and the assump­tion of the “supergenes” begs the ques­tion. The writer is under the impression that this author was led to his views by the belief that the egg is entirely undifferentiated. But the unfertilized egg is not homogeneous, on the contrary, it has a simple but definite physico­chemical structure which suffices to determine the first steps in the differentia­tion of the organism. Of course, if we suppose as do v. Uexküll and Driesch that the egg has no structure, the development of structure becomes a difficult problem—but this is not the real situa­tion.

2. Claude Bernard does not mention the possibility of explaining the harmony or apparent design in the organism on the basis of the theory of evolu­tion, he simply considers the problem as outside of biology. It was probably clear to him as it must be to everyone with an adequate training in physics that natural selec­tion does not explain the origin of varia­tion. Driesch and v. Uexküll consider the Darwinian theory a failure. We may admit that the theory of a forma­tion of new species by the cumulative effect of aimless fluctuating varia­tions is not tenable because fluctuating varia­tion is not hereditary; but this would only demand a slight change in the theory; namely a replacement of the influence of fluctuating varia­tion by that of equally aimless muta­tions. With this slight modifica­tion which is proposed by de Vries,5 Darwin’s theory still serves the purpose of explaining how without any pre-established plan only purposeful and harmonious organisms should have survived. It must be said, however, that any theory of life phenomena must be based on our knowledge of the physico­chemical constitu­tion of living matter, and neither Darwin nor Lamarck was concerned with this. Moreover, we cannot consider any theory of evolu­tion as proved unless it permits us to trans­form at desire one species into another, and this has not yet been accomplished.

It may be of some interest to point out that we do not need to make any definite assump­tion concerning the mechanism of evolu­tion and that we may yet be able to account for the fact that the surviving organisms are to all appearances harmonious. The writer pointed out that of all the 100,000,000 conceivable crosses of teleost fish (many of which are possible) not many more than 10,000, i. e., about one-hundredth of one per cent., are able to live and propagate. Those that live and develop are free from the grosser type of disharmonies, the rest are doomed on account of a gross lack of harmony of the parts. These latter we never see and this gives us the erroneous concep­tion that harmony or “design” is a general character of living matter. If anybody wishes to call the non-viability of 9999/100 per cent. of possible teleosts a process of weeding out by “natural selec­tion” we shall raise no objec­tion, but only wish to point out that our way of explaining the lack of design in living nature would be valid even if there were no theory of evolu­tion or if there had never been any evolu­tion.

3. v. Uexküll is perfectly right in connecting the problem of design in an organism with Mendelian heredity. The work on Mendelian heredity has shown that an extremely large number of independently transmissible Mendelian factors help to shape the individual. It is not yet proven that the organism is nothing but a mosaic of Mendelian factors, but no writer can be blamed for considering such a possibility. If we assume that the organism is nothing but a mosaic of Mendelian characters it is difficult indeed to understand how they can force each other into a harmonious whole6; even if we make ample allowance for the law of chance and the corresponding wastefulness in the world of the living. But it is doubtful whether this idea of the rôle of Mendelian factors is correct. The facts of experi­mental embryology strongly indicate the possibility that the cytoplasm of the egg is the future embryo (in the rough) and that the Mendelian factors only impress the individual (and variety) characters upon this rough block. This idea is supported by the fact that the first development—in the sea urchin to the gastrula stage inclusive—is independent of the nucleus, which is the bearer of the Mendelian factors. Not before the skeleton or mesenchyme is formed in the sea urchin egg is the influence of the nucleus noticeable. This has been shown in the experi­ments of Boveri in which an enucleated fragment of an egg was fertilized with a spermato­zoön of a foreign species. If this is generally true, it is conceivable that the generic and possibly also the species characters of organisms are determined by the cytoplasm of the egg and not by the Mendelian factors.

In any case, we can state today that the cytoplasm contains the rough preforma­tion of the future embryo. This would show then that the idea of the organism being a mosaic of Mendelian characters which have to be put into place by “supergenes” is unnecessary. If the egg is already the embryo in the rough we can imagine the Mendelian factors as giving rise to specific substances which go into the circula­tion and start or accelerate different chemical reac­tions in different parts of the embryo, and thereby call forth the finer details characteristic of the variety and the individual. The idea that the egg is the future embryo is supported by the fact that we can call forth a normal organism from an unfertilized egg by artificial means; while it is apparently impossible to cause the spermato­zoön to develop into an organism outside the egg.

4. The influence of the whole on the parts is nowhere shown more strikingly than in the field of regenera­tion. It is known that pieces cut from the plant or animal may give rise to new growth which in many cases will restore somewhat the original organism. Instead of asking what is the cause of this so-called regenera­tion we may ask, why the same pieces do not regenerate as long as they are parts of the whole. In this form the mysterious influence of the whole over its parts is put into the foreground. We shall see that growth takes place in certain cells when certain substances in the circula­tion can collect there. The mysterious influence of the whole on these parts consists often merely of the fact that the circulating specific or non-specific substances—we cannot yet decide which—will in the whole be attracted by certain spots and that this will prevent them from acting on other parts of the organism. If such parts are isolated the substances can no longer flow away from these parts and the parts will begin to grow. It thus becomes utterly unnecessary to endow such organisms with a “directing force” which has to elaborate the isolated parts into a whole.

5. The same difficulty which we have discussed in regard to morphogenesis exists also in connec­tion with those instincts which preserve the life of the organism and of the race. The reader need only be reminded of all the complicated instincts of mating by which sperm and eggs are brought together; or those by which the young are prevented from starva­tion to realize the apparently desperate problems in store for a mechanist, to whom the assump­tion of design is meaningless. And yet we are better off in regard to our knowledge of the instincts than we are in regard to morphogenesis, as in the former we can show that the apparent instincts in some cases obey simple physico­chemical laws with almost mathematical accuracy. Since the validity of the law of gravita­tion has been proved for the solar system the idea of design in the motion of the planets has lost its usefulness, and this fact must serve us as a guide wherever we attempt to put science beyond the possibility of mysticism. As soon as we can show that a life phenomenon obeys a simple physical law there is no longer any need for assuming the action of non-physical agencies. We shall see that this has been accomplished for one group of animal instincts; namely those which determine the rela­tion of animals to light, since these are being gradually reduced to the law of Bunsen and Roscoe. This law states that the chemical effect of light equals the product of intensity into dura­tion of illumina­tion. Some authors object to the tendency toward reducing everything in biology to mathematical laws or figures; but where would the theory of heredity be without figures? Figures have been responsible for showing that the laws of chance and not of design rule in heredity. Biology will be scientific only to the extent that it succeeds in reducing life phenomena to quantitative laws.

Those familiar with the theories of evolution know the extensive rôle ascribed to the adapta­tions of organisms. The writer in 1889 called atten­tion to the fact that reac­tions to light—e. g., positive helio­tropism—are found in organisms that never by any chance make use of them; and later that a great many organisms show definite instinctive reac­tions towards a galvanic current—galvano­tropism—although no organism has ever had or ever will have a chance to be exposed to such a current except in laboratory experi­ments. This throws a different light upon the seemingly purposeful character of animal reac­tions. Heliotropism depends primarily upon the presence of photo­sensitive substances in the eye or the epidermis of the organism, and these substances are inherited regardless of whether they are useful or not. It is only a metaphor to call reac­tions resulting from the presence of photo­sensitive substances “adapta­tion.” In this book other examples are given which show that authors have too often spoken of adapta­tion to environ­ment where the environ­ment was not responsible for the phenomena. The blindness of cave animals and the resistance of certain marine animals to higher concentra­tions of sea water are such cases. Cuénot speaks of “preadapta­tion” to express this rela­tion. The fact is that the “adapta­tions” often existed before the animal was exposed to surroundings where they were of use. This relieves us also of the necessity of postulating the existence of the inheritance of acquired characters, although it is quite possible that the future may furnish proof that such a mode of inheritance exists.

6. We have mentioned that according to Claude Bernard two groups of phenomena occur in the living organism: (1) the phenomena of vital crea­tion or organizing synthesis (especially in the egg and during development); (2) the phenomena of death or organic destruc­tion. These two processes are briefly discussed in the first and last chapters.

These introductory remarks may perhaps make it easier for the reader to retain the thread of the main ideas in the details of experi­ments and tables given in this book.

CHAPTER II

THE SPECIFIC DIFFERENCE BETWEEN LIVING AND DEAD MATTER AND THE QUESTION OF THE ORIGIN OF LIFE

1. Each organism is characterized by a definite form and we shall see in the next chapter that this form is determined by definite chemical substances. The same is true for crystals, where substance and form are definitely connected and there are further analogies between organisms and crystals. Crystals can grow in a proper solu­tion, and can regenerate their form in such a solu­tion when broken or injured; it is even possible to prevent or retard the forma­tion of crystals in a supersaturated solu­tion by preventing “germs” in the air from getting into the solu­tion, an observa­tion which was later utilized by Schroeder and Pasteur in their experi­ments on spontaneous genera­tion. However, the analogies between a living organism and a crystal are merely superficial and it is by pointing out the fundamental differences between the behaviour of crystals and that of living organisms that we can best understand the specific difference between non-living and living matter. It is true that a crystal can grow, but it will do so only in a supersaturated solu­tion of its own substance. Just the reverse is true for living organisms. In order to make bacteria or the cells of our body grow, solu­tions of the split products of the substances composing them and not the substances themselves must be available to the cells; second, these solu­tions must not be supersaturated, on the contrary, they must be dilute; and third, growth leads in living organisms to cell division as soon as the mass of the cell reaches a certain limit. This process of cell division cannot be claimed even metaphorically to exist in a crystal. A correct apprecia­tion of these facts will give us an insight into the specific difference between non-living and living matter. The forma­tion of living matter consists in the synthesis of the proteins, nucleins, fats, and carbohydrates of the cells, from the split products. To give an historical example, Pasteur showed that yeast cells and other fungi could be raised on the following sterilized solu­tion: water, 100 gm., crystallized sugar, 10 gm., ammonium tartrate, 0.2 gm. to 0.5 gm., and fused ash from yeast, 0.1 gm.7 He undertook this experi­ment to disprove the idea that protein or organic matter in a state of decomposi­tion was needed for the origin of new organisms as the defenders of the idea of spontaneous genera­tion had maintained.

2. That such a solu­tion can serve for the synthesis of all the compounds of living yeast cells is due to the fact that it contains the sugars. From the sugars organic acids can be formed and these with ammonia (which was offered in the form of ammonium tartrate) may give rise to the forma­tion of amino acids, the “building stones” of the proteins. It is thus obvious that the synthesis of living matter centres around the sugar molecule. The phosphates are required for the forma­tion of the nucleins, and the work of Harden and Young suggests that they play also a rôle in the alcoholic fermenta­tion of sugar.

Chlorophyll, under the influence of the red rays of light, manufactures the sugars from the CO₂ of the air. This makes it appear as though life on our planet should have been preceded by the existence of chlorophyll, a fact difficult to understand since it seems more natural to conceive of chlorophyll as a part or a product of living organisms rather than the reverse. Where then should the sugar come from, which is a constituent of the majority of culture media and which seems a prerequisite for the synthesis of proteins in living organisms?

The investiga­tions of Winogradsky on nitrifying,8 sulphur and perhaps also on iron bacteria have to all appearances pointed a way out of this difficulty. It seemed probable that there were specific micro-organisms which oxidized the ammonia formed in sewage or in the putrefac­tion of living matter, but the attempts to prove this assump­tion by raising such a nitrifying micro-organism on one of the usual culture media, all of which contained organic compounds, failed. Led by the results of his observa­tions on sulphur bacteria it occurred to Winogradsky that the presence of organic compounds stood in the way of raising these bacteria, and this idea proved correct. The bacteria oxidizing ammonia to nitrites were grown on the following medium; 1 gm. ammonium sulphate, 1 gm. potassium phosphate, 1 gm. magnesium carbonate, to 1 litre of water. From this medium, which is free from sugar and contains only constituents which could exist on the planet before the appearance of life, the nitrifying bacteria were able to form sugars, fatty acids, proteins, and the other specific constituents of living matter. Winogradsky proved, by quantitative determina­tion, that with the nitrifica­tion an increase in the amount of carbon compounds takes place. “Since this bound carbon in the cultures can have no other source than the CO₂ and since the process itself can have no other cause than the activity of the nitrifying organism, no other alternative was left but to ascribe to it the power of assimilating CO₂.”9 “Since the oxida­tion of NH₃ is the only source of chemical energy which the nitrifying organism can use it was clear a priori that the yield in assimila­tion must correspond to the quantity of oxidized nitrogen. It turned out that an approximately constant ratio exists between the values of assimilated carbon and those of oxidized nitrogen.” This is illustrated by the results of various experi­ments as shown in Table I.

TABLE I

It is obvious that 1 part of assimilated carbon corresponds to about 35.4 parts oxidized nitrogen or 96 parts of nitrous acid.

These results of Winogradsky were confirmed in very careful experi­ments by E. Godlewski, Sr.10

The nitrites are further oxidized by another kind of micro-organisms into nitrates and they also can be raised without organic material.

Winogradsky had already previously discovered that the hydrogen sulphide which is formed as a reduc­tion product from CaSO₄ or in putrefac­tion by the activity of certain bacteria can be oxidized by certain groups of bacteria, the sulphur bacteria. Such bacteria, e. g., Beggiatoa, are also commonly found at the outlet of sulphur springs. They utilize the hydrogen sulphide which they oxidize to sulphur and afterwards to sulphates, according to the scheme:

The sulphuric acid is at once neutralized by carbonates.

Winogradsky assumes that the oxida­tion of H₂S by the sulphur bacteria is the source of energy which plays the same rôle as the oxida­tion of NH₃ plays in the nitrifying bacteria, or the oxida­tion of carbon compounds—sugar and others—in the case of the other lower and higher organisms. Winogradsky has made it very probable that sulphur bacteria do not need any organic compounds and that their nutri­tion may be accomplished with a purely mineral culture medium, like that of the nitrite bacteria. On the basis of this assump­tion they should also be able to form sugars from the CO₂ of the air.

Nathanson11 discovered in the sea water the existence of bacteria which oxidize thiosulphate to sulphuric acid. They will develop if some Na₂S₂O₃, is added to sea water. These bacteria can only develop if CO₂ from the air is admitted or when carbonates are present. For these organisms the CO₂ cannot be replaced by glucose, urea, or other organic substances. Such bacteria must therefore possess the power of producing sugar and starch from CO₂ without the aid of chlorophyll. Similar observa­tions were made by Beijerinck on a species of fresh-water bacteria.12

Finally the case of iron bacteria may briefly be mentioned though Winogradsky’s views are not accepted by Molisch.

We may, therefore, consider it an established fact that there are a number of organisms which could have lived on this planet at a time when only mineral constituents, such as phosphates, K, Mg, SO₄, CO₂, and O₂ besides NH₃, or SH₂, existed. This would lead us to consider it possible that the first organisms on this planet may have belonged to that world of micro-organisms which was discovered by Winogradsky.

If we can conceive of this group of organisms as producing sugar, which in fact they do, they could have served as a basis for the development of other forms which require organic material for their development.

In 1883 the small island of Krakatau was destroyed by the most violent volcanic erup­tion on record. A visit to the islands two months after the erup­tion showed that “the three islands were covered with pumice and layers of ash reaching on an average a thickness of thirty metres and frequently sixty metres.”13 Of course all life on the islands was extinct. When Treub in 1886 first visited the island, he found that blue-green algæ were the first colonists on the pumice and on the exposed blocks of rock in the ravines on the mountain slopes. Investiga­tions made during subsequent expedi­tions demonstrated the associa­tion of diatoms and bacteria. All of these were probably carried by the wind. The algæ referred to were according to Euler of the nostoc type. Nostoc does not require sugar, since it can produce that compound from the CO₂ of the air by the activity of its chlorophyll. This organism possesses also the power of assimilating the free nitrogen of the air. From these observa­tions and because the Nostocaceæ generally appear as the first settlers on sand the conclusion has been drawn that they or the group of Schizophyceæ to which they belong formed the first settlers of our planet.14 This conclusion is not quite safe since in the settlement of Krakatau as well as in the first colonizing of sand areas the nature of the first settler is determined chiefly by the carrying power of wind (or waves and birds).

We may now return from this digression to the real object of our discussion, namely that the nutritive solu­tions of organisms must be very dilute and consist of the split products of the complicated compounds of which the organisms consist. The examples given sufficiently illustrate this statement.

The nutritive medium of our body cells is the blood, and while we take up as food the complicated compounds of plants or animals, these substances undergo a diges­tion, i. e., a splitting up into small constituents before they can diffuse from the intestine into the blood. Thus the proteins are digested down to the amino acids and these diffuse into the blood as demonstrated by Folin and by Van Slyke. From here the cells take them up. The different proteins differ in regard to the different types of amino acids which they contain. While the bacteria and fungi and apparently the higher plants can build up all their different amino acids from ammonia, this power is no longer found in the mammals which can form only certain amino acids in their body and must receive the others through their food. As a consequence it is usually necessary to feed young animals on more than one protein in order to make them grow, since one protein, as a rule, does not contain all the amino acids needed for the manufacture of all the proteins required for the forma­tion of the material of a growing animal.15

3. The essential difference between living and non-living matter consists then in this: the living cell synthetizes its own complicated specific material from indifferent or non-specific simple compounds of the surrounding medium, while the crystal simply adds the molecules found in its supersaturated solu­tion. This synthetic power of trans­forming small “building stones” into the complicated compounds specific for each organism is the “secret of life” or rather one of the secrets of life.

What clew have we in regard to the nature of this synthetic power? We know that the comparatively great velocity of chemical reac­tions in a living organism is due to the presence of enzymes (ferments) or to catalytic agencies in general. Some of these catalytic agencies are specific in the sense that a given catalyzer can accelerate the reac­tion of only one step in a complicated chemical reac­tion. While these enzymes are formed by the action of the body they can be separated from the body without losing their catalytic efficiency. It was a long time before scientists succeeded in isolating the enzyme of the yeast cell which causes the alcoholic fermenta­tion of sugar; and this gave rise to the premature statement that it was not possible to isolate this enzyme since it was bound up with the life of the yeast cell. Such a statement was even made by a man like Pasteur, who was usually a model of restraint in his utterances, and yet the work of Buchner proved him to be wrong.

The general mechanism of the action of the hydrolyzing enzymes is known. The old idea of de la Rive, that a molecule of enzyme combines transitorily with a molecule of substrate; the further idea, which may possibly go back to Engler, that the molecule of substrate is disrupted in the “strain” of the new combina­tion and that the broken fragments fall off or are easily knocked off by collision from the ferment molecule which is now ready to repeat the process, seems to be correct. On the assump­tion that the velocity of enzyme reac­tion is propor­tional to the mass of the enzyme and that de la Rive’s idea was correct, Van Slyke and Cullen were able to calculate the coefficients of the velocity of enzyme reac­tions for the fermenta­tion of urea and other substances, and the agreement between calculated and observed values was remarkable.16

While the hydrolytic action of enzymes is thus clear the synthesis in the cell is still a riddle. An interesting sugges­tion was made by van’t Hoff, who in 1898 expressed the idea that the hydrolytic enzymes should also act in the opposite direc­tion, namely synthetically. Thus it should not only be possible to digest proteins with pepsin but also to synthetize them from the products of diges­tion with the aid of the same enzyme. This expecta­tion was based on the idea that the enzyme did not alter the equilibrium between the hydrolyzed and non-hydrolyzed part of the substrate but only accelerated the rate with which the equilibrium was reached. Van’t Hoff’s idea omitted, however, the possibility that in the transitory combina­tion between enzyme molecule and substrate a change in the molecular configura­tion of the substrate or in the distribu­tion of intramolecular strain may take place. The first apparently complete confirma­tion of van’t Hoff’s sugges­tion appeared in the form of the synthesis of maltose from grape sugar by the enzyme maltase, which decomposes maltose into grape sugar. By adding the enzyme maltase from yeast to a forty per cent. solu­tion of glucose Croft Hill17 obtained a good yield of maltose. It turned out, however, that what he took for maltose was not this compound but an isomer, namely isomaltose, which has a different molecular configura­tion and cannot be hydrolyzed by the enzyme maltase.

Lactose is hydrolyzed from kephyr by an enzyme lactase into galactose and glucose; by adding this enzyme to galactose and glucose a synthesis was obtained not of lactose but of isolactose; the latter, however, is not decomposed by the enzyme lactase.

E. F. Armstrong has worked out a theory which tries to account for this striking phenomenon by assuming “that the enzyme has a specific influence in promoting the forma­tion of the biose which it cannot hydrolyze.”18 The theory is very ingenious and seems supported by fact. This then would lead to the result that certain hydrolytic enzymes may have a synthetic action but not in the manner suggested by van’t Hoff.

The principle enunciated by Armstrong, that in the synthetic action of hydrolytic enzymes not the original compound but an isomer is formed which can not be hydrolyzed by the enzyme, may possibly be of great importance in the understanding of life phenomena. It shows us how the cell can grow in the presence of hydrolytic enzymes and why in hunger the disintegra­tion of the cell material is so slow. It was at first thought that the forma­tion of isomers contradicted the idea of the reversible action of enzymes, but this is not the case; on the contrary, it supports it but makes an addi­tion which may solve the riddle of what Claude Bernard called the creative action of living matter. We shall come back to this problem in the last chapter.

Kastle and Loevenhart demonstrated the synthesis of a trace of ethylbutyrate by lipase if the latter enzyme was added to the products of the hydrolysis of ethylbutyrate, ethyl alcohol, and butyric acid by the same enzyme.19 Taylor20 obtained the synthesis of a slight amount of triolein