Part 42

The case is the same in respect to the sound-producing apparatus of many insects. Many grasshoppers produce sounds by fiddling with the thigh of the hind leg on the wing, others by rubbing one anterior wing upon the other, and, indeed, always with one particular vein in one upon a particular vein in the other. One of these serves as the bow, the other as the string, of the violin, and the bow is furnished with teeth (Fig. 91), ranged beside each other in a long row, which have the same function as the colophonium of the violin, that is, to grasp and release the strings alternately, and thus to produce resounding vibrations. My pupils, Dr. Petrunkewitsch and Dr. Georg von Guaita, have recently proved that these teeth have arisen as modifications of the hairs which are scattered everywhere over the wing and leg. But only in this one place, on the so-called 'stridulating-vein,' have they been modified to form stridulating teeth (_schr_). Thus this vein must be capable of transmissible variation by itself alone, that is, there must be parts contained in the germ-plasm, the variation of which causes a variation solely of this individual vein and its hairs, possibly even a variation only on certain hairs on this vein.

On the other hand, there are also large regions, whole cell-masses of the body, which in all probability vary only _en bloc_, as, for instance, the milliards of blood-cells in Man, the hundreds of thousands or millions of cells in the liver and other glandular organs, the thousands of fibres of a muscle, or of the sinews or fascia, the cells of a cartilage or a bone, and so on. In all these cases a single determinant, or at least a few in the germ-plasm, may be enough. But in numerous cases it is impossible to say how large the region is which is controlled by a single determinant, and it is, of course, of no importance to the theory. In unicellular organisms the determinants will control parts of cells, in multicellular organisms often whole cells and groups of cells.

Perhaps an inference as to the nature of the determinants may be drawn from this with some probability, in as far as mere parts of cells may be supposed to have simpler determinants than whole cells and groups of cells. The determinants in the chromosomes of unicellular organisms may therefore often consist of single biophors, so that in this case the conception of biophors would coincide with that of determinants. In multicellular organisms, on the other hand, I should be inclined on the whole to picture the determinant as a group of biophors, which are bound together by internal forces to form a higher vital unity. This determinant must live as a whole, that is, assimilate, grow, and multiply by division, like every vital unit, and its biophors must be individually variable, so that the separate parts of a cell controlled by them may also be capable of transmissible variation. That they are so, every highly differentiated cell of a higher animal teaches us; even the smelling-hairs of a crab exhibit a stalk, a terminal knob, and an internal filament, and many muscle-, nerve-, and gland-cells are much more complex in structure.

LECTURE XVIII

THE GERM-PLASM THEORY (_continued_)

Structure of the germ-plasm--Vital affinities--Division--O. Hertwig's chief objections to this theory--Male and female eggs in the Phylloxera show differential division--Dispersal of the germ-plasm in the course of Ontogeny--Active and passive state of the determinants--Predetermination of cells--There are no determinants of characters--Liberation of the determinants--Accessory idioplasm--Herbst's lithium larvæ--Plant galls--Cells with several facultative determinants--Connective tissue in vertebrates--Mesoderm cells of Echinoderms--Sexual dimorphism--Female and male ids--Polymorphism (_Papilio merope_)--Ants.

I HAVE endeavoured to prove that the germ-substance proper must be looked for in the chromatin of the nucleus of the germ-cell, and more precisely still in those ids or chromosomes which we conceive of as containing the primary constituents (_Anlagen_) of a complete organism. Such ids in larger or smaller numbers make up the whole germ-plasm of a germ-cell, and each id in its turn consists of primary constituents or determinants, i.e. of vital units, each of which determines the origin and development of a particular part of the organism. We have now to make an attempt to picture to ourselves how these determinants predetermine those cells or cell-groups to which they correspond. In doing so we have to fall back upon mere hypotheses, and in stating any such hypothesis I wish expressly to emphasize that I am only following up one of the possibilities which our imaginative faculty suggests. Nevertheless, to endeavour to form such a conception is certainly not without use, for it is only by elaborating a theory to the utmost that we are able to use it in application to concrete cases, thus stimulating the search for corroboratory or contradictory facts, and leading gradually to a recognition of the gaps or mistakes in the theory.

The first condition that must be fulfilled in order that a determinant may be able to control a cell or cell-group is that it should succeed in getting into it. It must be guided through the numerous cell-divisions of ontogeny so that it shall ultimately come to lie in the cells which it is to control. This presupposes that each determinant has from the very beginning its definite position in relation to the rest, and that the germ-plasm, therefore, is not a mere loose aggregate of determinants, but that it possesses a structure, an architecture, in which the individual determinants have each their definite place. The position of the determinants in relation to one another cannot be due to chance, but depends partly on their historical development from earlier ancestral determinants, partly on internal forces, such as we have already assumed for keeping the determinants together. We may best designate these hypothetical forces 'affinities,' and in order to distinguish them from mere chemical affinities we may call them 'vital.' There must be forces interacting among the different determinants which bind them together into a living whole, the id, which can assimilate, grow, and multiply by division, in the same manner as we were forced to assume for the smaller units, the biophors and single determinants. In the ids, however, we can observe the working of these forces quite directly, since each chromosome splits into two halves of equal size at every nuclear division, and not through the agency of external forces, e.g. the attraction which we may assume to be exerted by the fibrils of the nuclear spindle, but through purely internal forces, often long before the nuclear spindle has been formed at all.

But if the determinants must separate from each other in the course of development so as to penetrate singly into the cells they are to control, the id must not only have the power of dividing into daughter-ids of identical composition, it must also possess the power of dividing under certain influences into dissimilar halves, so that the two daughter-ids contain different complexes of determinants. The first mode of division of the id, and with it of the nucleus and of the cell, I call _erbgleich_, or integral, the second _erbungleich_, or differential. The first form of multiplication is the usual one, which we observe everywhere when unicellular organisms divide themselves into two equal daughter-units, or when the cells of multicellular bodies produce their like by division into two. The second is not directly observable, because a dissimilarity of the daughter-cells, as long as it lies only in the idioplasm, cannot be actually seen; it can only be inferred from the different rôle which the two daughter-cells play in the building up of the individual. When, for instance, one of two sister-cells of the embryo gives rise to the cells of the alimentary canal and the other to those of the skin and the nervous system, I infer that the mother-cell divided its nuclear substance in a differential way between the two daughter-cells, so that one contained the determinants of the endoderm, the other those of the ectoderm; or when a red and a black spot lie side by side and under exactly the same conditions on the wing of a butterfly, I conclude that the ancestral cells of these two spots have divided differentially, so that one received the 'red,' the other the 'black' determinants. Our eyes can perceive no difference between the nuclear substance of the two cells, but the same is true of the chromosomes of the paternal and maternal nuclei in the fertilized ovum, although we know in this case that they contain different tendencies. In any case we are not justified in concluding from the apparent similarity of the chromosome-halves in nuclear division that there cannot be differential division. The theoretical possibility that there is such differential division cannot be disputed; indeed, I am inclined to say that it is more easily imagined than the division of the ids into absolutely similar halves. Both are only conceivable on the assumption that there are forces which control the mutual position of the determinants in the ids, that is, on the assumption of 'affinities.' I shall not follow this further, but that there are forces operative within the ids which are still entirely unknown to us is proved at every nuclear division by the _spontaneous_ splitting of the chromosomes.

It has been objected to my theory that such a complex whole as the id could not in any case multiply by division, since there is no apparatus present which can, in the division into two daughter-units, re-establish the architecture disturbed by the growth. But this objection is only valid if we refuse to admit the combining forces, the 'vital affinities' within the ids, and the same is true for the smaller vital units. An ordinary chemical molecule cannot increase by division; if it be forcibly divided it falls into different molecules altogether; it is only the living molecule, that is, the biophor, which possesses this marvellous property of growth and division into two halves similar to itself and to the ancestral molecule, and we may argue from this that in the division of the ids forces of attraction and repulsion must likewise be operative[19].

[19] In my book _The Germ-Plasm_ I have already assumed the existence of 'forces of attraction' in the determinants and biophors, as in the cells. I did not, indeed, enter into details, but I argued on the same basis as now (_Germ-Plasm_, p. 64, English edition). My critics have overlooked this.

I see no reason why we should not assume the existence of such forces, when we make the assumption that the hundreds of atoms which, according to our modern conceptions, compose the molecule of albumen and determine its nature, are kept by affinities in this definite and exceedingly complex arrangement. Or must we suppose that between the atom-complex of the molecule and the next higher atom-complex of the biophor, determinant, and id there is an absolute line of demarcation, so that we must assume quite different forces in the latter from those we conceive of as operative in the former? The biophor is ultimately only a group of molecules, the determinants a group of biophors, the id a group of determinants, and all the three inferred stages of vital organization only become real units through the forces operating within them and combining them into a whole. What compels the chromatin granules of the resting nucleus to approach each other at the time of cell-division, to unite into a long, band-like thread, and what is it that subsequently causes this thread to break up again into a definite number of pieces? Obviously only internal forces of which we know nothing further than that they are operative.

We shall see later that this assumption of vital affinities must be made not only in regard to the cells, but also in regard to entire organisms whose parts are united by an internal bond, and whose co-ordination is regulated by forces of which we have as yet no secure knowledge. In the meantime we may designate these forces by the name of 'vital affinities.'

It must be admitted, however, that some objections of a fundamental nature have been urged against the assumption of a differential nuclear division of the hereditary substance. O. Hertwig holds that the assumption of differential division is essentially untenable, because it is contradictory to 'one of the first principles of reproduction,' for 'a physiologically fundamental character of every living being is the power of maintaining its species.'

This certainly seems so, but a closer examination shows that this 'principle,' although correct enough when taken in a very general sense, does not really cover the facts, and is therefore incapable of supporting the inferences drawn from it. If the proposition expressed the whole truth there could have been no evolution from the primitive organisms to higher ones, every living being must have simply reproduced exact copies of itself. Whether the transformations of species have been sudden or gradual, whether they have been brought about by large steps or by very small ones, they could only have come about by breaking through this so-called 'principle' of like begetting like. In fact, we may with more justice maintain the exact converse of the principle, and say that 'no living being is able to produce an exact copy of itself,' and this is true not only of sexual, but of asexual reproduction.

In ontogeny we see exactly the same thing. There are no two daughter-cells of a mother-cell which are exactly alike, and the differences between them, if they increase in the same direction, may lead in later descendants to entire differences of structure. Indeed the whole process of development depends on such an augmentation of the differences between two daughter-cells--on differences which proceed from within and are definitely pre-established. Here, again, the facts do not justify us in making a dogma of the proposition that it is a 'fundamental power' of every living being to maintain its species by producing replicas of itself. If we look at two directly successive cell-generations, we can hardly, it is true, in most cases, perceive any difference between them, just as in the generations of species; but if we compare the end of a long cell-lineage with the beginning, then the difference is marked, and we recognize that the difference is due to a gradual summing up of minute, invisible deviations. In my opinion these steps of difference cannot possibly depend merely on direct external influences; they proceed rather from the hereditary substance the cell receives from the ovum, which, therefore, in order to attain to such many-sided and far-reaching differentiation, must have undergone a frequently repeated splitting up of its qualities. That this splitting is not merely a variation to which the whole of the hereditary substance of the daughter-cells is uniformly subject, according to the influences dependent on their position in relation to other cells of the embryo, will be made clear from the case of the Ctenophora referred to in the next lecture. A scarcely less striking example is that of those animals in which the ova contain the primary constituents for only one sex, in which, in other words, there are 'male' ova and 'female' ova. This is the case, for instance, among Rotifers, and in plant-lice such as the vine-pest, _Phylloxera_. Here the eggs from which males develop are smaller than those which produce females. The primary constituents for both male and female are not, as in most animals, contained in the same ovum, to be liberated on one side or the other by influences unknown to us, but in each ovum there is only one of the two sets of primary constituents present, and in this case, therefore, the development of hermaphrodites, which not infrequently occur in other animals, would be impossible. But all these ova have been produced by one primitive reproductive cell, and consequently, at one of the divisions implied in the multiplication of this first cell, a separation of the male from the female primary constituents must have taken place, that is, a differential division of hereditary substance, for which no external and no intercellular influences can possibly account.

If there is, then, a differential division of the ids and with them of the whole idioplasm, the germ-plasm of the fertilized ovum must be broken up in the course of ontogeny into ever smaller groups of determinants. I conceive of this as happening in the following manner.

In many animals the fertilized ovum divides at the first segmentation into two cells, one of which gives rise predominantly to the outer, the other to the inner germinal layer, as in molluscs, for instance. Let us now assume that this is the case altogether, so that one of the first two blastomeres gives rise to the whole of the ectoderm, the other to the whole of the endoderm; we should here have a differential division, for the developmental import (the 'prospective' of Driesch) of the primitive ectoderm-cell is quite different from that of the primitive endoderm-cell, the former giving origin to the skin and the nervous system, with the sense organs, while the second gives rise to the alimentary canal, with the liver, &c. Through this step in segmentation, I conclude, the determinants of all the ectoderm-cells become separated from those of the endoderm-cells; the determinant architecture of the ids must be so constructed in such species that it can be segregated at the first egg-cleavage into ectodermal and endodermal groups of determinants. Such differential divisions will always occur in embryogenesis when it is necessary to divide a cell into two daughter-cells having dissimilar developmental import, and consequently they will continue to occur until the determinant architecture of the ids is completely analysed or segregated out into its different kinds of determinants, so that each cell ultimately contains only one kind of determinant, the one by which its own particular character is determined. This character of course consists not merely in its morphological structure and chemical content, but also in its collective physiological capacity, including its power of division and duration of life[20].

[20] Emery has lately called attention to another direct proof of the existence of differential cell- and nucleus-division. According to observations made by Giardina, in the water-beetle (_Dytiscus_), one primitive ovum-cell gives rise, through four successive divisions, to fifteen nutritive cells and one well-defined ovum-cell. But only half of the nuclear substance takes part in these divisions, the rest remains inactive in a condensed, cloudy condition. 'The meaning of the whole process is obviously that the germ-plasm mass as a whole is handed over to the ovum-cell, while the nutritive cells receive only the nuclear constituents which belong to them' (_Biol. Centralbl._, May 15, 1903).

But embryogenesis does not proceed by differential divisions alone, for integral divisions are often interpolated between them, always, for instance, when in a bilateral animal an embryonic cell has to produce by division into two a corresponding organ for the right and left sides of the body; for instance, in the division of the primitive genital cell into the rudiments of the right and left reproductive organs, or in the division of the primitive mesoderm-cell into the right and left initial mesoderm-cell, but also later on in the course of embryogenesis, when, for instance, the right or the left primitive reproductive cell multiplies into a large number of primitive germ-cells, or in the multiplication of the blood-cells, or of the epithelial cells of a particular region; in short, whenever mother and daughter-cells have the same developmental import, that is, when they are to become nothing more than they already are. In all such cases a similar group of determinants, or a similar single determinant, must in the nuclear division penetrate into each of the two daughter-cells.

It is in this way, it seems to me, that the determinants gain entrance into the cells they are to control, by a regulated splitting up of the ids into ever smaller groups of determinants, by a gradual analysis or segregation of the germ-plasm into the idioplasms of the different ontogenetic stages. When I first developed this idea I assumed that the splitting process would in all cases set in at the same time, namely, at the first division of the ovum. But since then, in the controversies excited by the theory, many facts have been brought to light which prove that the ova of the different animal groups behave differently, and that the splitting up of the aggregate of primary constituents may sometimes begin later--but I shall return to this later on.

If we accept the segregation hypothesis, which is similar in purport to that advanced by Roux as the' mosaic theory,' it must strike us as remarkable that the chromatin mass of the nucleus does not become notably smaller in the course of ontogeny, and even ultimately sink to invisibility. Determinants lie far below the limits of visibility, and if there were really only a single determinant to control each cell there would be no chromatin visible in such a case. This objection has in point of fact been urged against me, although I expressly emphasized in advance the assumption that the determinants are continually multiplying throughout the whole ontogeny, so that in proportion as the number of the _kinds_ of determinants lying within a cell diminishes the number of resting determinants of each kind increases. When, finally, only one kind of determinant is present there is a whole army of determinants of that kind.

It follows from this conception of the gradual segregation of the components of the id in the course of development that we must attribute to the determinants two different states, at least in regard to their effect upon the cell in which they lie: an active state, in which they control the cell, and a passive state, in which they exert no influence upon the cell, although they multiply. From the egg onwards, therefore, a mass of determinants is handed on by the cell-divisions of embryogenesis, which will only later become active.

My conception of the manner in which the determinants become active is similar to that suggested by De Vries in regard to his 'Pangens,' very minute vital particles which play a determining part in his 'pangen theory,' similar to that filled by the determinants in my germ-plasm theory. It seems to me that the determinants must ultimately break up into the smallest vital elements of which they are composed, the biophors, and that these migrate through the nuclear membrane into the cell-substance. But there a struggle for food and space must take place between the protoplasmic elements already present and the newcomers, and this gives rise to a more or less marked modification of the cell-structure.