The Organism as a Whole, from a Physicochemical Viewpoint

Carrying the assumption still farther, these authors \ were able to show that each individual character has in all probability a definite location in the chromosome, so that it seems as if each individual chromosome 1 The number of hereditary characters examined to test the theory was over 130. consisted of a series of smaller chromosomes, each of which may be a factor in the determination of a hereditary character which is transmitted according to Mendel's law of segregation. Biology has thus reached in the chromosome theory of Mendelian heredity an atomistic conception, according to which independent material determiners for hereditary characters exist in a linear arrangement in the chromosomes.

4. We are not concerned in this volume with the many applications of the theory of heredity to the breeding of plants, animals, and man; the reader will find a discussion of these topics in the numerous writings of the special workers on genetics.1 We are, however, interested in the bearing this work has on the conception of the organism. Two questions present themselves: Is the organism nothing but a mosaic of hereditary characters determined essentially by definite elements located in the chromosomes; and if this be true, what makes a harmonious whole organism out of this kaleidoscopic assortment? We call it a kaleidoscopic assortment since a glance at the list of hereditary characters found in one chromosome, according to Morgan, shows that there is apparently

xBateson, W., Mendel's Principles of Heredity, 3d ed., 1913; Davenport, Chas. B., Heredity in Relation to Eugenics, 1911. Pearl, R., Modes of Research in Genetics. no physiological or chemical connection between them, and second : How can a factor contained in the chromosome determine a hereditary character of the organism? To the first question we venture to offer the answer which has been already suggested in various chapters of this book, that the cytoplasm of the egg is the future embryo in the rough ; and that the factors of heredity in the sperm only act by impressing the details upon the rough block. This metaphor will receive a more definite meaning by the answer to the second question. The characters which follow Mendelian heredity are morphological features as well as instincts. For the former we have already had occasion to show in previous chapters to what extent they depend upon the internal secretions or the existence of specific compounds in the circulation, and the same is true for the instincts (Chapters VIII and X). This then leads us to the suggestion that these determiners contained in the chromosomes give rise each to the formation of one or more specific substances which influence various parts of the body. We probably do not notice all the effects in each case, but when a special organ is affected in a conspicuous way, we connect the factor with this organ or the special feature of the organ which is altered, and speak of a determiner or factor for that organ, or for one of its characters. We also understand in this way why outside conditions should be able to overcome the hereditary tendency \

in certain cases, for instance why the influence of certain hereditary factors for pigmentation should depend upon temperature as E. Baur observed. The view, according to which the determiners in the chromosomes only tend to give special characters to the embryo or to the adult while the cytoplasm of the egg may be considered the real embryo, receives some support from the fact that the first development of the egg is purely maternal, even if the egg nucleus has been replaced by sperm of a different species. If an egg of a sea urchin be cut into two pieces, one with and one without a nucleus, and the enucleated piece be fertilized with the sperm of a different species of sea urchin, the blastula and gastrula stages are purely maternal and only the skeleton of the pluteus stage begins to betray the influence of the foreign sperm inasmuch as this skeleton is purely paternal, according to Boveri. In all experiments on hybridization it has been found that the rate of cell division of the egg is a purely maternal character. Thus when fish eggs of a species, in which the rate of first segmentation of the egg is about eight hours, are fertilized with sperm of a species for which the same process requires about thirty minutes or less at the same temperature, the rate of segmentation is again about eight hours. There is then no chromosome influence noticeable in the early development.

franciscanus and purpuratus,1 are crossed, certain features of the skeleton of the embryo, e. g., the so-called cross-bars, are a dominant, inasmuch as they are found in purpuratus and both the crosses, while they are absent in franciscanus. The development prior to the formation of the skeleton is purely maternal. These observations again lend support to the idea that the Mendelian factors of heredity must have the embryo to work on and that the organism is not to be considered a mere mosaic of Mendelian factors. This is further supported by the idea that the species specificity resides in the proteins of the unfertilized egg (see Chapter III), and it is quite likely that this species specificity decides which type of animal should arise from an egg. The idea had been suggested that the factors which determine the future character might be ferments or enzymes, or substances from which such ferments develop. A. R. Moore2 pointed out that the cross-bars in the skeleton of the hybrid between S. purpuratus and franciscanus develop more slowly than in the pure breed and that this should be expected if the determiners were enzymes. Since the pure purpuratus has two determiners for the development of the cross-bars (from both egg and sperm), the hybrids only one (from either

' Loeb, J.,King, W. O. R., and Moore, A. RM Arch.f. Entwcklngsmech., 1910, xxix., 354. These experiments have been repeated at different seasons of the year and in different years and have been found to be constant. egg or sperm), the pure purpuratus should have twice the enzyme mass of the hybrid. It is known that the velocity of a chemical reaction increases in proportion with the mass (or in some cases in proportion with the square root of the mass) of the enzyme; the crossbars should therefore develop faster in the pure than in the hybrid breeds, as was observed by Moore. It was, however, not possible to obtain quantitative data.

On the other hand, it is obvious that this reasoning would not hold for all cases. Thus when beans with violet flowers are crossed with white-flowered beans the hybrids are pale blue, which indicates that the hybrids have less pigment than the pure violet. Now we know that the mass of enzyme does not influence the chemical equilibrium but only the velocity of the reaction. The hybrids and pure violets differ, however, in the mass of violet pigment formed, that is to say, in regard to the equilibrium. Hence the idea that the determiners are enzymes or give rise to enzymes is probably not applicable to cases of this type.

The experiments on the heredity of pigments are at present almost the only ones which can be used for an analysis of the chemical nature of the character and its possible determiner. The important work of G. Bertrand1 and of Chodat2 on the production of black pigment in the cells of animals and plants with the aid of enzymes has paved the way for such work. Bertrand has shown that tyrosine (^-oxyphenylaminopropionic acid) is transformed into a black pigment by an enzyme tyrosinase which occurs in numerous organisms and is obviously the cause of pigment and colouration in a great number of species. This discovery was utilized in the study of the heredity of pigments by Miss Durham, Gortner,1 and very recently by On- slow.2' The latter showed that from the skins of certain coloured rabbits and mice a peroxidase can be extracted which behaves like a tryosinase toward tyrosine in the presence of hydrogen peroxide. This peroxidase was found in the skins of black agouti, chocolate and blue rabbits, but not in yellow or orange rabbits. The recessive whiteness in rabbits and mice according to this author is due to the lack of the peroxydase. There exists a dominant whiteness in the English rabbit which is due to a tyrosinase inhibitor which destroys the activity of the tyrosinase "and the dominant white bellies of yellow and agouti rabbits are due to the same cause." " Variations in coat colour are probably due to a quantitative rather than to a qualitative difference in the pigment present."

One point might still be mentioned since it may help to overcome a difficulty in visualizing the connection between the localization of a factor in the chromosome and the production of a comparatively large quantity of a specific chemical compound, e. g., a chromogen or a tyrosinase. We must remember that all the cells of an organism have identical chromosomes, so that a factor for an enzyme like tyrosinase is contained in every cell throughout the whole body. It is likely, however, that the same factor (which we may conceive to be a definite chemical compound) will find a different chemical substrate to work on in the cells of different organs of the body, since the different organs differ in their chemical composition. Thus it is conceivable that in the production of tyrosinase or of tyrosine not a single chromomere of one single cell is engaged, but the sum total of all these individual chromomeres of all the cells in one or several organs of the body. The writer has added this remark especially in consideration of the fact that some authors seem to feel that the chromosome conception of heredity is incompatible with a physicochemical view of this process.

Since we have mentioned this difficulty which some writers seem to find in the chromosome theory of Mendelian heredity, it may be added that a single factor may suffice to determine a series of complicated reflexes. Thus the heliotropic reactions of animals are due to the presence of photosensitive substances, and it suffices for the hereditary transmission of the complicated purposeful reactions based on these tropisms that a factor for the formation of the photosensitive substance should exist. x

5. Another point should be emphasized, namely that for Mendelian heredity it is immaterial whether the character is introduced by the spermatozoon or by the egg. This fact which Mendel himself already recognized is in full harmony with the conclusion that the chromosomes and not the cytoplasm are the bearers of Mendelian heredity, since only in respect to the chromosome constitution are egg and sperm alike, while they differ enormously in regard to the mass of protoplasm they carry. We can, therefore, be tolerably sure that wherever we deal with a hereditary factor which is determined by the egg alone the cytoplasm of the latter is partly or exclusively responsible for the result.

We have already mentioned the fact that the rate of segmentation of the egg is such a character. Yet this character is as definite as any Mendelian character, and it would be as easy to discriminate two species of eggs by the time required from insemination to the beginning of cell division as it would be by any Mendelian character of their parents. The application of our modern knowledge of heredity to human affairs has been discussed in a very original

way by Bateson in his address before the British Association in Sydney to which the reader may be referred.1 i. The idea that the organism as a whole cannot be explained from a physicochemical viewpoint rests most strongly on the existence of animal instincts and will. Many of the instinctive actions are "purposeful,1* i. e.j assisting to preserve the individual and the race. This again suggests "design" and a designing "force," which we do not find in the realm of physics. We must remember, however, that there was a time when the same "purposefulness" was believed to exist in the cosmos where everything seemed to turn literally and metaphorically around the earth, the abode of man. In the latter case, the anthropo- or geocentric view came to an end when it was shown that the motions of the planets were regulated by Newton's law and that there was no room left for the

1 Ideas similar to those expressed in this chapter may be found in the writer's former book Comparative Physiology of the Brain and Comparative Psychology, New York, 1900, and in the books by George Bohn, La Naissance de V Intelligence, Paris, 1909, and La nouvelle Psychologic animale, Paris, 1911. activities of a guiding power. Likewise, in the realm of instincts when it can be shown that these instincts may be reduced to elementary physicochemical laws the assumption of design becomes superfluous.

If we look at the animal instincts purely as observers we might well get the impression that they cannot be explained in mechanistic terms. We need only consider what mysticism apparently surrounds all those instincts by which the two sexes are brought together and by which the entrance of the spermatozoon into the egg is secured ; or the remarkable instincts which result in providing food and shelter for the young generation. We have already had occasion to record some cases of instincts which suggest the possibility of physicochemical explanation; for example the curious experiment of Steinach on the reversal of the sexual instincts of the male whose testes had been exchanged for ovaries. There is little doubt that in this case the sexual activities of each sex are determined by specific substances formed in the interstitial tissue of the ovary and testes. The chemical isolation of the active substances and an investigation of their action upon the various parts of the body would seem to promise further progress along this line.

Marchal's observations on the laying of eggs by the naturally sterile worker wasps are a similar case. The fact that such workers lay eggs when the queen is removed or when they are taken away from the larvae may be considered as a manifestation of one of those wonderful instincts which form the delight of readers of Maeterlinck's romances from insect life. Imagine the social foresight of the sterile workers who when the occasion demands it "raise" eggs to preserve the stock from extinction!. And yet what really happens is that these workers, when there are no larvae, can consume the food which would otherwise have been devoured by the larvae; and some substance contained in this food induces the development of eggs in the otherwise dormant ovaries. What appeared at first sight as a mysterious social instinct is revealed as an effect comparable to that of thyroid substance upon the growth of the legs of tadpoles in Gudernatsch's experiment (Chapter VII).

2. If we wish to show in an unmistakable way the mechanistic character of instincts we must be able to reduce them to laws which are also valid in physics. That instinct, or rather that group of instincts, for which this has been accomplished are the reactions of organisms to light. The reader is familiar with the tendency of many insects to fly into the flame. It can be shown that many species of animals, from the lowest forms up to the fishes, are at certain stages — very often the larval stage — of their existence, slaves of the light. When such animals, e. g., the larvse of the barnacle or certain winged plant lice or the caterpillars of certain butterflies, are put into a trough or

test-tube illuminated from one side only, they will rush to the side from which the light comes and will continue to do this whenever the orientation of the trough or test-tube to the light is changed; while they will be held at the window side of the vessel if the light or the position of the vessel remains unchanged. This instinct to get to the source of light is so strong that, e. g., the caterpillars of Porihesia chrysorrhcea die of starvation on the window side of the vessel, with plenty of food close behind. This powerful " instinct" is, as we intend to show, in the last analysis, the expression of the Bunsen-Roscoe law of photochemical reactions. A large number of chemical reactions are induced or accelerated by light, and the Bunsen-Roscoe law shows that the chemical effect is in these cases, within certain limits, equal to the product of the intensity into the duration of illumination.

The "attraction" or "repulsion" of animals by the light had been explained by the biologists in an anthropomorphic way by ascribing to the animals a "fondness" for light or for darkness. Thus Graber, who had made the most extensive experiments, gave as a result the statement that animals which are fond of - light are also fond of blue while they hate the red, and those which are fond of the "dark" are fond of red and hate the blue.1 In 1888 the writer published a paper

1 Graber, V., Grundlinien zur Erforschung des Helligkeitsund Farbensinnes der Tiere. Prag, 1884. in which he pointed out that the so-called fondness of animals for light and blue and for dark and red was simply a case of an automatic orientation of animals by the light comparable to the turning of the tips of a plant towards the window of the room in which the plant is raised. x The phenomenon of a plant bending or growing to the source of light is called positive heliotropism (while we speak of negative heliotropism in all cases in which the plant turns away from the light, as is observed in many roots). The writer pointed out that animals which go to the light are positively heliotropic (or phototropic) and do so because they are compelled automatically by the light to move in this direction, while he called those animals which move away from the light negatively heliotropic; they are automatically compelled by the light to move away from it. What the light does is to direct the motions of the animals and to explain this the following theory was proposed. Animals possess photosensitive elements on the surface of their bodies, in the eyes, or occasionally also in epithelial cells of their skin. These photosensitive elements are arranged symmetrically in the body and through nerves are connected with symmetrical groups of muscles. The light causes chemical changes in the

eyes (or the photosensitive elements of the skin). The mass of photochemical reaction products formed in the retina (or its homologues) influences the central nervous system and through this the tension or energy production of the muscles. If the rate of photochemical reaction is equal in both eyes this effect on the symmetrical muscles is equal, and the muscles of both sides of the body work with equal energy; as a consequence the animal will not be deviated from the direction in which it was moving. This happens when the axis or plane of symmetry of the animal goes through the source of light, provided only one source of light be present. If, however, the light falls side wise upon the animal, the rate of photochemical reaction will be unequal in both eyes and the rate at which the symmetrical muscles of both sides of the body work will no longer be equal; as a consequence the direction in which the animal moves will change. This change will take place in one of two ways, according as the animal is either positively or negatively heliotropic ; in the positively heliotropic animal the resulting motion will be toward, in the negatively heliotropic from, the light. Where we have no central nervous system, as in plants or lower animals, the tension of the contractile or turgid organs is influenced in a different way, which we need not discuss here.

The reader will perceive that according to the writer's theory two agencies are to be considered in these reactions: first, the symmetrical arrangement of the photosensitive and the contractile organs, and second, the relative masses of the photochemical reaction products produced in both retinas or photosensitive organs at the same time. If a positively heliotropic animal is struck by light from one side, the effect on tension or energy production of muscles connected with this eye will be such that an automatic turning of the head and the whole animal towards the source of light takes place; as soon as both eyes are illuminated equally the photochemical reaction velocity will be the same in both eyes, the symmetrical muscles of the body will work equally, and the animal will continue to move in this direction. In the case of the negatively heliotropic animal the picture is the same except that if only one eye is illuminated the muscles connected with this eye will work less energetically. The theory can be nicely tested for negatively heliotropic animals in the larvas of the blowfly when they are fully grown, and for positively heliotropic animals on the larvae of Balanus, and many other organisms.

One of the difficulties in identifying the motions of animals to or from the light with the positive and negative heliotropism of plants consisted in the fact that plants are mostly sessile (and respond to a onesided illumination with heliotropic curvatures to or from the light), while most animals are free moving and respond to the one-sided illumination by being turned and compelled to move to or from the light. This difficulty was overcome by the observation that

sessile animals like the hydroid Eudendrium (Fig. 43) or the tube worm Spirographis (Fig. 44) react to a oneorganisms like the swarmspores of algae move to or from the source of light as do free-swimming animals. 3. The writer suggested in 1897* that the light acts chemically in the heliotropic reactions and in 1912 that the heliotropic reactions probably follow the law of Bunsen and Roscoe,2 and it was possible to confirm this idea by direct experiments.3 This law states that the photochemical effect of light equals i t where i is the intensity of the light and / the duration of illumination. The experiments were carried out on young regenerating polyps of Eudendrium by measuring the time required to cause fifty per cent, of the polyps to bend to the source of light. The intensity of light was varied by altering the distance of the source of light from the polyps. Table VI gives the result.

Time Required to Cause Fifty Per Cent, of the Polyps to Bend towards the Source of Light We must therefore conclude that the heliotropic curvature of the polyps is determined by a photochemical action of the light. The light brings about or accelerates a chemical reaction which follows the Bunsen— Roscoe law. As soon as the product of this reaction on one side of the polyp exceeds that on the other by a certain quantity, the bending occurs. When the product it is the same for symmetrical spots of the organism no bending can result. This is what our theory suggested.

It is very difficult to prove directly the applicability of the Bunsen-Roscoe law for free-moving animals, but it can be shown that intermittent light is as effective as constant light of the same intensity, provided that the total duration of the illumination by the intermittent light is equal to that of the constant light, and the duration of the intermission is sufficiently small (Talbot's law). Talbot's law is in reality only a modification of the Bunsen-Roscoe law. Ewald has proved in a very elegant way the applicability of Talbot's law to the orientation of the eyestalk of Daphnia.1 This makes it probable that the law of Bunsen-Roscoe underlies generally the heliotropic reaction of animals.

It is of importance for the theory of the identity of the heliotropism of animals and plants that in the latter organisms the law of Bunsen and Roscoe is also applicable. This had been shown previously by Froschel1 and by Blaauw.2 In the following table are given the results of Blaauw's experiments on the applicability of the Bunsen-Roscoe law for the heliotropic curvature of the seedlings of oats (Avena saliva). The time required to cause heliotropic curvatures for intensities of light varying from 0.00017 to 26520 metre-candles was measured. The product it, namely metre-candles-seconds, varies very little (between 1 6 and 26).

It is, therefore, obvious that the blind instinct which forces animals to go to the light, e. g., in the case of the moth, is identical with the instinct which makes a plant bend to the light and is a special case of the same law of Bunsen and Roscoe which also explains the photochemical effects in inanimate nature; or in other words, the will or tendency of an animal to move towards the light can be expressed in terms of the Bunsen-Roscoe law of photochemical reactions.

The writer had shown in his early publications on light effects that aside from the heliotropic reaction of animals, which as we now know depends upon the product of the intensity and duration of illumination, there is a second reaction which depends upon the sudden changes in the intensity of illumination. These latter therefore obey a law of the form: Effect = f On).1 Jennings has maintained that the heliotropic reactions of unicellular organisms are all of this kind, but investigations by Torrey and by Bancroft2 on Euglena have shown that Jennings's statements were based on incomplete observations.

4. In these experiments only one source of light was applied. " When two sources of light of equal intensity and distance act simultaneously upon a heliotropic animal, the latter puts its median plane at right angles to the line connecting the two sources of light."3 This fact has been amply verified by Bohn, by Parker and his pupils, and especially by Bradley Patten, who used it to compare the relative efficiency of two different lights. The behaviour of the animals under the influence of two lights is a confirmation of our theory of heliotropism inasmuch as the animal moves in such a direction that the symmetrical elements of the surface of the body are struck by light of the same intensity at the same angle, so that as a consequence equal masses of photosensitive substances are produced in symmetrical elements of their eyes or skin in equal times. The effect on the symmetrical muscles will be identical. As soon as one of the lights is a little stronger the animal will deviate towards this light, in case it is positively heliotropic and towards the weaker light if it is negatively heliotropic. This deviation again is not the product of chance but follows a definite law as Patten1 has recently shown. He used the negatively heliotropic larvae of the blowfly. These larvae were made to record their trail while moving under the influence of the two lights. The results of the measurements of 2500 trails showing the progressive increase in angular deviation of the larvae (from the perpendicular upon the line connecting the two lights), with increasing differences between the lights, are given in the following table. Since the deviation or angular deflection of the larvae is towards the weaker of the two lights it is marked negative.