Part 43

It might be supposed that the structure of these biophors corresponded in advance to certain constituent parts of the cell, that there were, for instance, muscle biophors, which make the muscle what it is, or that the plant-cells acquired their chlorophyll-making organs through chlorophyll biophors. De Vries gave expression to this view in his 'pangen theory,' and I confess that at the time there seemed to me much to be said for it, but I am now doubtful whether its general applicability can be admitted. In the first place, it does not seem to me theoretically necessary to assume that the particles which migrate into the cell-bodies should themselves be chlorophyll or muscle particles; they may quite well be only the architects of these, that is to say, particles which by their co-operation with the elements already present in the cell-body give rise to chlorophyll or muscle substance. As we are as yet unacquainted with the forces which dominate these smallest vital particles, as well as the processes which lead to the histological differentiation of the cells, it is useless in the meantime to make any further hypotheses in regard to them. But in any case the biophors which transform the general character of the embryonic cells into the specific character of a particular tissue-cell must themselves possess a specific structure different from that of other biophors, for they must keep up the continuity of the structures handed on from ancestors, chlorophyll and muscle-substance and the like, since we cannot assume that these structures, so peculiar and so complex in their chemical and physical constitution, are formed afresh, so to speak, by spontaneous generation in each new being, as De Vries has very rightly emphasized. A specific biophor, for instance, of muscle substance will produce this substance as soon as it has found its way into the appropriate cell-body, even though it may not be a contractile element itself.

To this must be added that the structure of the body and the distinctive features of an organism do not depend merely on the histological differentiation of the cells, but quite as much on their number and arrangement, and on the size and on the frequency of repetition of certain parts. These distinctive characters are just as constant and as strictly transmissible, and may be as heritably variable as those which depend on specific cell-differentiation, and they must therefore likewise be determinable by definite elements of the germ-plasm. Obviously enough, however, these elements are not of the same nature as the known specific histological elementary particles; they can be neither nerve-, muscle-, nor gland-biophors. They must rather be vital units of such a kind that they communicate to the cells and lineage of cells, into whose bodies they migrate from within the nucleus, a definite vital power, that is, an organization which regulates the size, form, number of divisions, and so on, of these cells--in short their whole prospective significance. Always, however, they act in co-operation with the cell-body into which they have penetrated.

Throughout we must hold ourselves aloof from the idea that 'characters' are transmissible. It is customary, indeed, to speak as if this were so, and it is also necessary, because we can only recognize the 'characters' of a body, and not the essential 'nature' on which these characters depend; but the determinants are not seed-grains of individual characters, but co-determinants of the nature of the parts which they influence. There are not special determinants of the size of a cell, others of its specific histological differentiation, and still others of its duration of life, power of multiplication, and so on; there are only determinants of the whole physiological nature of a cell, on which all these and many other 'characters' depend. For this reason alone I should object to the assumption that the determinants of the germ are ready-made histological substances. That is as unlikely as that their groups in the germ-plasm are 'miniature models' of the finished parts of the body.

I conceive of the process of cell-differentiation as follows: at every cell-stage in the ontogeny determinants attain to maturity, and break up so that their biophors can migrate into the cell-bodies, so that the quality of each cell is thus kept continually under control, and may be more or less modified, or may remain the same. By the 'maturity' of a determinant I mean its condition when by continual division it has increased in number to such a point that its disintegration into biophors and their migration into the cell-substance can take place.

One more point I must touch upon here, the question of the 'liberation' or 'stimulation' of the determinants. The activity of an organ never depends on itself alone; the contraction of a muscle is induced by a nerve stimulus or by an electric current; the activity of the nerve-cells of the brain requires the continual stimulus of the blood-stream, and cannot continue to exist without it; the specific sensory-nerves and sense-cells of the eye, ear, olfactory organ, and so on, are all prompted to activity by adequate stimuli. The same is true in regard to the determinants, they must be 'liberated' if they are to distribute themselves and migrate into the cell-body; and we have to ask how that happens, whether it is possibly due only to their own internal condition, which again would, of course, depend on the nutritive conditions of the cell in which they lie, or whether it is perhaps due to some specific stimulus which is necessary in addition to the fact of 'maturity,' just as a muscle is always ready to contract, yet only does so when it is affected by a specific stimulus.

From the very first, therefore, I have considered whether it would not be better to elaborate the determinant theory in such a way that it would not be necessary to assume a disintegration of the id in the course of ontogeny, but simply to conceive of every expression of activity on the part of a determinant as dependent on a specific stimulus, which in many cases can only be supplied by a definite cell, that is, by internal influences, and in other cases may be due to external influences.

Darwin assumed the first of these alternatives in his theory of Pangenesis, which we have still to outline. In it he attributes to his 'gemmules' the power of giving rise to particular cells, which, however, they can only accomplish when they reach the cells which are the genetic antecedents of those which the gemmules are to control. Translated into the language of our theory this view would read as follows: the whole complex of determinants is contained within every cell, as it is contained in the germ-cell, but at every stage of ontogeny, that is, in each of the developing cells, only the determinant which is to control the immediately successive cells is 'liberated,' and that through the stimulus which the specific nature of the cell supplies to the determinant. In that case there would necessarily be in every species of animal as many specific stimuli for determinants as there are determinants. This appeared to me improbable, and I rejected the hypothesis because of the enormous number of specific stimuli which it demands, but also on other grounds which will be touched upon in the course of these lectures.

Although the assumption of an autonomic dissolution of the determinant complexes of the id in the course of ontogeny seems to me imperative, I do not by any means reject the interposition of liberating stimuli, indeed I regard their co-operation as indispensable. Later on we shall discuss cases in which it is definitely demonstrable that there may be two alternative sets of homologous determinants present in a cell, but that on any occasion only one of these becomes active, a fact which we can only explain on the assumption that only one of these is affected by the specific liberating stimulus. The phenomena of regeneration, of polymorphism, of germ-cell formation, &c., compel us to the assumption that numerous cells, even after the completion of the building up of the body, contain two or more kinds of determinants, as in a sense inactive 'accessory idioplasm,' each of which could control the cell alone, though in reality it only does control it when it is affected by the appropriate liberating stimulus. I stated this view some years ago when I attempted to define more precisely the rôle played by 'external influences as developmental stimuli[21]'. It is not, then, that I underrate the importance of external influences on the organism, but I believe that a still larger part of the determination of what shall happen at a particular point depends on the primary constituents, and that these are not alike at all parts of the body.

[21] _Äussere Einflüsse als Entwicklungsreize_ [External Influences as Stimuli to Development], Jena, 1894.

All living processes, therefore, both those of growing and of differentiation, depend always upon the interaction of external and internal factors, of the environment and the living substance, and the resultants of the interaction, namely, the structure of the body and its parts must necessarily turn out differently, not only when the germ-substance is different, but when the essential conditions of development are changed. But that the constitution of the germ is by far the most potent factor, and that the nature of the results of development depends on it in a much greater degree than on the external conditions, has long been known. The conditions, such as warmth, may vary within certain limits, and yet the frog's egg becomes a frog; though it does not follow that the result of development may not be modified through certain changes in the conditions. The interesting experiments made by Herbst with the eggs of sea-urchins have shown that, in artificially altered sea-water in which sodium-salts are to a slight extent replaced by lithium-salts, these eggs develop into larvæ which only remotely suggest the normal structure, and diverge widely from it both in external shape and in the form of the skeleton.

Such larvæ are not able to survive, but soon perish; they are, however, of great interest from the point of view of our theory, for they show that determinants do not bring forth the same structure under all circumstances, but that, as I have already said, they are vital units of specific composition, which play a part in the course of development, and give rise under normal external influences to normal parts, while under unusual influences, if these are not such as to prohibit development altogether, they may give rise to an abnormally formed part. It must not be forgotten that most composite parts--indeed, strictly speaking, all the parts--of an animal are not controlled by a single determinant, but by the many which successively determine the character of the cells and define the path of development of the part in question. There are no determinants of 'characters,' but only of parts; the germ-plasm no more contains the determinants of a 'crooked nose' than it does those of a butterfly's tailed wing, but it contains a number of determinants which so control the whole cell-group in all its successive stages, leading on to the development of the nose, that ultimately the crooked nose must result, just as the butterfly's wing with all its veins, membranes, tracheæ, glandular cells, scales, pigment deposits, and pointed tail arises through the successive interposition of numerous determinants in the course of cell-multiplication.

But in both processes we must presuppose _normal conditions of development_. In regard to the butterfly we know that abnormal conditions, such as cold during the pupal period, can cause considerable variation in the colour and marking of the wing, and in regard to the nose it can scarcely be doubted that, for instance, persistent pressure on the nasal region would result in a considerable deviation from the hereditary form.

The case of the lithium-larvæ is similar. Here the chemical conditions of the first segmentation-cells are modified by the presence of the lithium-salts, and the determinants which make their way out of the nucleus in the first and in subsequent cell-generations find an unusual soil for their activity, which diverges further and further from the normal with each successive cell-generation. Thus the whole animal is abnormally formed. The process may perhaps be compared to a plant which is negatively geotropic and positively heliotropic, that is, the stem of which tends to grow straight upwards, while all its green parts grow towards the light. If a plant of this kind have light shed on it from one side only, the stem with its leaves will grow obliquely towards that side. If the plant be then turned round so that it receives light from the other side, the stem in its further growth will curve in a direction opposite to that which it took before, and so by continually changing the position of the plant in relation to the light one could--theoretically at least--produce a plant with a zigzag stem. But this would not furnish any evidence against the presence of determinants; there are no 'upright determinants' any more than there are 'zigzag determinants' or 'crooked nose determinants,' but there are determinants controlling the nature of the cells which give rise, under normal conditions of development, to the straight stem, under abnormal conditions to the zigzag stem, or to a flat nose instead of a crooked one, and so on.

This consideration should make it clear that plant-galls are not in the remotest degree a stone of stumbling for the determinant theory, as some have supposed. Of course there can be no 'gall-determinants,' for galls are not transmissible adaptations of the plants on which they occur; they arise solely through the larvæ of the gall-insect which has laid its eggs within the tissues of the plant. But the specific nature of the different kinds of plant-cells, predetermined by their determinants, is such that, through the abnormal influences exercised upon them by the larvæ, they are compelled to a special reaction which results in the formation of galls. It is marvellous enough that these abnormal stimuli should be so precisely graded and adjusted that such a specifically definite structure should result, and in this case there is obviously a very different state of matters from that obtaining in most other processes of development, in which the chief determining factor is rather implied in the nature of the idioplasm, that is, of the determinants, than in the nature of the external influences. Here, however, the specific structure of the gall depends mainly on the quality, variety, and successive effects of the external influences or stimuli. In discussing the influences of surroundings I shall return once more to the galls.

My determinants have generally been regarded as if they were like grains of seed, from which either nothing may arise, under unfavourable conditions, or just the particular kind of plant from which the seed itself originated.

This simile is, however, to be taken _cum grano salis_. The whole ovum is certainly comparable to a grain of seed, but single determinants or groups of determinants will always be able to adapt themselves to different influences, and to remain active even under slightly abnormal conditions, though in that case the resulting structures may be somewhat divergent. This relative plasticity is indispensable even in relation to the ceaseless mutual adaptations of the growing parts of the organism. Not only do the cells which live beside each other at the same time influence each other mutually, but the influence extends to the whole cell-lineage. No cell or group of cells develops independently of all the others in the body, but each has its ancestral series of cells on whose determinants it is so far dependent, since these have taken part in determining its own nature, in, so to speak, supplying the soil in which ultimately its own determinants will be sown from the nucleus, and whose influence modifies these last according to its quality. We might therefore say that every part is determined by all the determinants of its cell-ancestors.

If there be urged against the doctrine of determinants the undoubted fact of the dependence of individual development on external conditions, or the capacity that organisms have of functional adaptation, or especially the power that some parts of the organism have of taking a different form in response to different stimuli, I can only say that I see no reason why certain cells and masses of cells should not be adapted from the first for responding differently to different stimuli.

Therefore I see no contradiction of the determinant theory when, for instance, among the higher vertebrates, the cells of the connective tissue exhibit a great diversity of form, becoming a loose 'filling' connective tissue in one place, a tense fascia, ligament, or tendon tissue in another, according as they are subjected to slight pressure on all sides or to stronger pressure on one side. I see no difficulty in the fact that this connective tissue forms in one case bone-tissue with the most accurate adaptation of its microscopic structure to the conditions of stress and pressure which affect the relevant spot, or in another case cartilaginous tissue, when the cells are exposed to varying pressure (as on the surface of joints), or even that it gives rise to blood-vessels when the pressure of the circulating blood and the tension of the surrounding tissues supply the necessary stimulus. It is easy to see how important, indeed how necessary, the many-sidedness of these cells is for the organism, even leaving out of account such violent interference as the breaking of a bone, the irregular healing of broken ends of bones, new joint formation, and so on, and thinking only of the normal phenomena of growth. While the bone grows it is continually breaking up in the inside and forming anew on the surface, and this occurs through the power of the connective tissue-cells to form different tissues under different influences or stimuli.

We must therefore assume that there are side by side in the connective cells of higher vertebrates determinants of bone, of cartilage, of connective tissue in the narrower sense, and of blood-vessels, and that one or other of these is liberated to activity according to the stimulus affecting it. Phenomena occur also in the development of lower animals which lead us to the same assumption.

Among these is the remarkable behaviour of the primary mesoderm-cells in the young embryo (gastrula) of the Echinoderms (Fig. 92). At the point where the primitive gut or archenteron invaginates into the interior of the hitherto single-layered blastula (Fig. 92, _A_), some cells are separated off (_M_), and move independently, constantly multiplying the while, into the clear gelatinous fluid (_G_) which fills the cavity of the larva, and there they fix themselves, some on the outer ectodermic layer, others to the various regions and outgrowths of the archenteron (_Ms_). According as these cells have established themselves at one or another point, they become connective tissue, muscle, or skeleton cells of the dermis, or contribute to the muscular layer of the food-canal and water-vascular system, or, finally, become skeleton-forming cells of the calcareous ring which surrounds the gullet of the sea-cucumber. In all this there is nothing to indicate a determination of the cells in one direction; on the contrary it seems as if the fate of the individual cells depended on the chance conditions which may lead them to one place or to another.

There are thus three possibilities of development, three kinds of reaction, implied in these cells, which are all outwardly alike, and we can only understand their rôle in the building up of this very symmetrical animal if we assume that of these three only one is in each case liberated, by the specific stimulus exerted by the immediate surroundings of the cell, so that it may become, according to the chance position it takes up after its migration, either a skin-cell, a muscle-cell, or a skeleton-forming cell.

This case may be compared in some respects with the permanent colour-adaptation of those caterpillars, in regard to which Poulton demonstrated that they become almost black if they are reared on blackish-brown bark, light brown on light bark, and green if they are kept among leaves, and in all cases permanently so. In this case also the implicated pigment-cells of the skin may develop in three ways, according to whether this or that quality of the light releases this or that determinant.

But in many cases we do not know the quality of the liberating stimulus, and must content ourselves with imagining it. This is so in the case of dimorphism of the sexes. It is clear that in the males of a species the germ-cells develop quite otherwise than they do in the females, that different determining elements attain to activity in each sex, and since the primary constituents of both sexes must be contained in most animals in the ovum and in the spermatozoon, we must assume that in both there are at once 'ovogenic' and 'spermogenic' determinants, of which, however, only _one_ kind becomes active in a given individual. There are, however, both among plants and animals hermaphrodite individuals, in which both kinds of sexual products are developed simultaneously or successively.

It is not only the primary sexual characters, however, that compel us to the assumption of double determinants in the germ-plasm, the secondary sexual characters do so too. We know very well in relation to ourselves that 'the beautiful soprano voice of the mother may be transmitted through the son to the grand-daughter, and that the black beard of the father may pass through the daughter to the grandson.' Thus both kinds of sexual characters _must be present in every sexually differentiated being_, some visible, others latent. In animals the determinants are sometimes handed on from germ-plasm to germ-plasm through several generations in a latent state, and only make their appearance again in a subsequent generation. This is the case in the water-fleas (Daphnids) and the plant-lice (Aphides), in which several exclusively female generations succeed one another, and only in the last of them do males occur again side by side with the females.