The Organism as a Whole, from a Physicochemical Viewpoint

" 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." 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 spermatozoon, but apparently we cannot make a spermatozoon 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 heredi-

tary 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, t 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. Schafer'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, JDr. 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.

I. 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 so.ne 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 nonphysical 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: (i) 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.

1 Bernard C., Lemons sur les Phenombies de la Vie. Paris, 1885, i., 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. There is so to speak a pre-established design of each being and of each organ of such a kind that each phenomenon by itself depends upon the general forces of nature, but when taken in connection with the others it seems directed by some invisible guide on the road it follows and led to the place it occupies. . . .

We admit that the life phenomena are attached to physicochemical manifestations, but it is true that the essential is not explained thereby; for no fortuitous coming together of physicochemical phenomena constructs each organism after a plan and a fixed design (which are foreseen in advance) and arouses the admirable subordination and harmonious agreement of the acts of life. . . . We can only know the material conditions and not the intimate nature of life phenomena. We have therefore only to deal with matter and not with the first causes or the vital force derived therefrom. These causes are inaccessible to us, and if we believe anything else we commit an error and become the dupes of metaphors and take figurative language as real. . . . Determinism can never be but physicochemical determinism. The vital force and life belong to the metaphysical world.

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 Driesch1 and v. Uexkull,2 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. Uexkull suggests a kind of Platonic "idea" as a peculiar characteristic of life which accounts for the purposeful character of the organism.

v. Uexkull 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 1 Driesch, H., The Science and Philosophy of the Organism. 2 vols. The GifFord Lectures, 1907 and 1908.

av. Uexkull, J.f Bausteine zu einer biologischen Weltanschauung. Munchen, 1913. 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."1 v. Uexkull'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. Uexkull 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. Uexkull consider the Darwinian theory a failure. We may admit that the theory of a forma-

tion 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,1 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 nonviability of 99 i% 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. Uexkull 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 whole1; even if we make ample allowance for the law

1 This difficulty is also felt by mechanistic writers like Child, who on page 12 of his recent book on Senescence and Rejuvenescence (Chicago, 1915) makes the following remarks: "These theories of Weismann do not account satisfactorily for the peculiarly constant course and character of development and morphogenesis. If we follow them to their logical conclusion, which their authors have not done, we find ourselves forced to assume the existence of some sort of controlling and

of chance and the corresponding wastefulness in the world of the living. But it is doubtful whether this idea of the r61e 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 spermatozoon 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.

co-ordinating principle outside the units themselves and superior to them. If the units constitute the physicochemical basis of life, as their authors maintain, then this controlling principle, since it is an essential feature of life, must of necessity be something which is not physicochemical in nature. In short these theories lead us in the final analysis to the same conclusion as that reached by the neovitalists. If we are not content to accept this conclusion we must reject the theories." These last sentences do not exhaust all the possibilities, since the writer is trying to show in this book that the widest acceptance of the chromosome theory of heredity is compatible with a consistent physicochemical conception of the organism as a whole.

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 spermatozoon 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 cr 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 winch 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 nonphysical 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 role 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