Essays Upon Heredity and Kindred Biological Problems

If therefore the first segmentation nucleus contains, in its molecular structure, the whole of the inherited tendencies of development, it must follow that during segmentation and subsequent cell-division, the nucleoplasm will enter upon definite and varied changes which must cause the differences appearing in the cells which are produced; for identical cell-bodies depend, ceteris paribus, upon identical nucleoplasm, and conversely different cells depend upon differences in the nucleoplasm. The fact that the embryo grows more strongly in one direction than in another, that its cell-layers are of different nature and are ultimately differentiated into various organs and tissues,—forces us to accept the conclusion that the nuclear substance has also been changed in nature, and that such changes take place during ontogenetic development in a regular and definite manner. This view is also held by Strasburger, and it must be the opinion of all who seek to derive the development of inherited tendencies from the molecular structure of the germ-plasm, instead of from preformed gemmules.

We are thus led to the important question as to the forces by which the determining substance or nucleoplasm is changed, and as to the manner in which it changes during the course of ontogeny, and on the answer to this question our further conclusions must depend. The simplest hypothesis would be to suppose that, at each division of the nucleus, its specific substance divides into two halves of unequal quality, so that the cell-bodies would also be transformed; for we have seen that the character of a cell is determined by that of its nucleus. Thus in any Metazoon the first two segmentation spheres would be transformed in such a manner that one only contained the hereditary tendencies of the endoderm and the other those of the ectoderm, and therefore, at a later stage, the cells of the endoderm would arise from the one and those of the ectoderm from the other; and this is actually known to occur. In the course of further division the nucleoplasm of the first ectoderm cell would again divide unequally, e.g. into the nucleoplasm containing the hereditary tendencies of the nervous system, and into that containing the tendencies of the external skin. But even then, the end of the unequal division of nuclei would not have been nearly reached; for, in the formation of the nervous system, the nuclear substance which contains the hereditary tendencies of the sense-organs, would, in the course of further cell-division, be separated from that which contains the tendencies of the central organs, and the same process would continue in the formation of all single organs, and in the final development of the most minute histological elements. This process would take place in a definitely ordered course, exactly as it has taken place throughout a very long series of ancestors; and the determining and directing factor is simply and solely the nuclear substance, the nucleoplasm, which possesses such a molecular structure in the germ-cell that all such succeeding stages of its molecular structure in future nuclei must necessarily arise from it, as soon as the requisite external conditions are present. This is almost the same conception of ontogenetic development as that which has been held by embryologists who have not accepted the doctrine of evolution: for we have only to transfer the primary cause of development, from an unknown source within the organism, into the nuclear substance, in order to make the views identical.

It appears at first sight that the knowledge which has been gained by studying the indirect division of nuclei is opposed to such a view, for we know that each mother-loop of the so-called nuclear plate divides longitudinally into two exactly equal halves, which can be stained and thus rendered visible.

In this way each resulting daughter-nucleus receives an equal supply of halves, and it therefore appears that the two nuclei must be completely identical. This at least is Strasburger’s conclusion, and he regards such identity as a fundamental fact, which cannot be shaken, and with which all attempts at further explanation must be brought into accord.

How then can the gradual transformation of the nuclear substance be brought about? For such a transformation must necessarily take place if the nuclear substance is really the determining factor in development. Strasburger attempts to support his hypothesis by assuming that the inequality of the daughter-nuclei arises from unequal nutrition; and he therefore considers that the inequality is brought about after the division of the nucleus and of the cell. Strasburger has shown, in a manner which is above all criticism, that the nucleus derives its nutrition from the cell-body, but then the cell-bodies of the two ex hypothesi identical daughter-nuclei must be different from the first, if they are to influence their nuclei in different ways. But if the nucleus determines the nature of the cell, it follows that two identical daughter-nuclei which have arisen by division within one mother-cell cannot come to possess unequal cell-bodies. As a matter of fact, however, the cell-bodies of two daughter-cells often differ in size, in appearance, and in their subsequent history, and these facts are sufficient to prove that in such cases the division of the nucleus must have been unequal. It appears to me to be a necessary conclusion that, in such an instance, the mother-nucleus must have been capable of splitting into nuclear substances of differing quality. I think that, in his argument, Strasburger has over-estimated the support afforded by exact observations upon indirect nuclear division. Certainly the fact, discovered by Flemming, and more exactly studied by Balbiani and Pfitzner, that, in nuclear division, the loops split longitudinally, is of great and even of fundamental importance. Furthermore, the observations, conducted last year by van Beneden, on the process of fertilization in Ascaris, have given to Flemming’s discovery a clearer and more definite meaning than could have been at first ascribed to it. The discovery proves, in the first place, that the nucleus always divides into two parts of equal quantity, and further that in every nuclear division, each daughter-nucleus receives the same amount of nuclear substance from the father as from the mother; but, as it seems to me, it is very far from proving that the quality of the parent nucleoplasms must always be equal in the daughter-nuclei. It is true that the fact seems to prove this; and if we remember the description of the most favourable instance which has been hitherto discovered, viz. the process of fertilization in the egg of Ascaris, as represented by van Beneden, the two longitudinal halves of each loop certainly impress the reader as being absolutely identical (compare, for instance, loc. cit. Plate XIX, figs. 1, 4, 5). But we must not forget that we do not see the molecular structure of the nucleoplasm, but something which we can only look upon (when we remember how complex this molecular structure must be) as a very rough expression of its quantity. Our most powerful and best lenses just enable us to make out the form of separate stainable granules present in a loop which is about to divide: they appear as spheres and immediately after division as hemispheres. But according to Strasburger, these granules, the so-called microsomata, only serve for the nutrition of the nuclear substance proper, which lies between them unstainable, and therefore not distinctly visible. But even if these granules represent the true idioplasm, their division into two exactly equal parts would give us no proof of equality or inequality in their constitution: it would only give us an idea of their quantitative relations. We can only obtain proofs as to the quality of the molecular structure of the two halves by their effect on the bodies of the daughter-cells, and we know that these latter are frequently different in size and quality.

This point is so important that I must illustrate it by a few more examples. The so-called polar bodies (to be treated more in detail below) which are expelled during maturation from the eggs of so many animals, are true cells, as was first proved by Bütschli in Nematodes: their formation is due to a process of undoubted cell-division usually accompanied by a typical form of indirect nuclear division121. If any one is still in doubt upon this point, after the observations of Fol and Hertwig, he might easily be convinced of its truth by a glance at the figures (unfortunately too little known) which Trinchese122 has published, illustrating this process in the eggs of certain gastropods. The eggs of Amphorina coerulea are in every way suitable for observation, being entirely translucent, and having large distinct nuclei which differ from the green cytoplasm in colour. In these eggs two polar bodies are formed one after the other: and each of them immediately re-divides: hence it follows that four polar bodies are placed at the pole of the egg. But how is it that these four cells perish, while the nucleus, remaining in the yolk and conjugating with the sperm-nucleus, makes use of the whole body of the egg and developes into the embryo? Obviously because the nature of the polar body is different from that of the egg-cell. But since the nature of the cell is determined by the quality of the nucleus, this quality must differ from the very moment of nuclear division. This is proved by the fact that the supernumerary spermatozoa which sometimes enter the egg do not conjugate with the polar bodies. According to Strasburger’s theory, the objection might be urged that the different quality of the nuclei is here caused by the very different quantity of cytoplasm by which they are surrounded and nourished; but on the one hand the smallness of the cell-bodies which surround most polar globules must have some explanation, and this can only be found in the nature of the nucleus; and on the other hand the quantity of the cell-body which surrounds the polar globules of Amphorina is, as a matter of fact, somewhat larger than the sphere of green cytoplasm which surrounds the nucleus of the egg! The difference between the polar bodies and the egg-cell can thus only be explained on the supposition that, in the division of the nuclear spindle, two qualitatively different daughter-nuclei are produced.

There does not seem to be any objection to the view that the microsomata of the nuclear loops—assuming that these bodies represent the idioplasm—are capable of dividing into halves, equal in form and appearance, but unequal in quality. We know that this very process takes place in many egg-cells; thus in the egg of the earth-worm the first two segmentation spheres are equal in size and appearance, and yet the one forms the endoderm and the other the ectoderm of the embryo.

I therefore believe that we must accept the hypothesis that, in indirect nuclear division, the formation of unequal halves may take place quite as readily as the formation of equal halves, and that the equality or inequality of the subsequently produced daughter-cells must depend upon that of the nuclei. Thus during ontogeny a gradual transformation of the nuclear substance takes place, necessarily imposed upon it, according to certain laws, by its own nature, and such transformation is accompanied by a gradual change in the character of the cell-bodies.

It is true that we cannot gain any detailed knowledge of the nature of these changes in the nuclear substance, but we can very well arrive at certain general conclusions about them. If we may suppose, with Nägeli, that the molecular structure of the germ-idioplasm, or according to our terminology the germ-plasm, becomes more complicated according to the greater complexity of the organism developed from it, then the following conclusions will also be accepted,—that the molecular structure of the nuclear substance is simpler as the differences between the structures arising from it become less; that therefore the nuclear substance of the segmentation-cell of the earth-worm, which potentially contains the whole of the ectoderm, possesses a more complicated molecular structure than that of a single epidermic cell or nerve-cell. These conclusions will be admitted when it is remembered that every detail in the whole organism must be represented in the germ-plasm by its own special and peculiar arrangement of the groups of molecules (the micellae of Nägeli), and that the germ-plasm not only contains the whole of the quantitative and qualitative characters of the species, but also all individual variations as far as these are hereditary: for example the small depression in the centre of the chin noticed in some families. The physical causes of all apparently unimportant hereditary habits or structures, of hereditary talents, and other mental peculiarities, must all be contained in the minute quantity of germ-plasm which is possessed by the nucleus of a germ-cell;—not indeed as the preformed germs of structure (the gemmules of pangenesis), but as variations in its molecular constitution; if this be impossible, such characters could not be inherited. Nägeli has shown in his work, which is so rich in suggestive ideas, that even in so minute a space as the thousandth of a cubic millimetre, such an enormous number (400,000,000) of micellae may be present, that the most diverse and complicated arrangements become possible. It therefore follows that the molecular structure of the germ-plasm in the germ-cells of an individual must be distinguished from that of another individual by certain differences, although these may be but small; and it also follows that the germ-plasm of any species must differ from that of all other species.

These considerations lead us to conclude that the molecular structure of the germ-plasm in all higher animals must be excessively complex, and, at the same time, that this complexity must gradually diminish during ontogeny as the structures still to be formed from any cell, and therefore represented in the molecular constitution of its nucleoplasm, become less in number. I do not mean to imply that the nucleoplasm contains preformed structures which are gradually reduced in number as they are given off in various directions during the building-up of organs: I mean that the complexity of the molecular structure decreases as the potentiality for further development also decreases, such potentiality being represented in the molecular structure of the nucleus. The nucleoplasm, which in the grouping of its particles contains potentially a hundred different modifications of this substance, must possess far more numerous kinds and far more complex arrangements of such particles than the nucleoplasm which only contains a single modification, capable of determining the character of a single kind of cell. The development of the nucleoplasm during ontogeny may be to some extent compared to an army composed of corps, which are made up of divisions, and these of brigades, and so on. The whole army may be taken to represent the nucleoplasm of the germ-cell: the earliest cell-division (as into the first cells of the ectoderm and endoderm) may be represented by the separation of the two corps, similarly formed but with different duties: and the following cell-divisions by the successive detachment of divisions, brigades, regiments, battalions, companies, etc.; and as the groups become simpler so does their sphere of action become limited. It must be admitted that this metaphor is imperfect in two respects, first, because the quantity of the nucleoplasm is not diminished, but only its complexity, and secondly, because the strength of an army chiefly depends upon its numbers, not on the complexity of its constitution. And we must also guard against the supposition that unequal nuclear division simply means a separation of part of the molecular structure, like the detachment of a regiment from a brigade. On the contrary, the molecular constitution of the mother-nucleus is certainly changed during division in such a way that one or both halves receive a new structure which did not exist before their formation.

My opinion as to the behaviour of the idioplasm during ontogeny, not only differs from that of Nägeli, in that the latter maintains that the idioplasm only undergoes changes in its ‘conditions of tension and movement,’ but also because he imagines this substance to be composed of the preformed germs of structures (‘Anlagen’). Nägeli’s views are obviously bound up with his theory of a continuous network of idioplasm throughout the whole body; perhaps he would have adopted other conclusions had he been aware of the fact that the idioplasm must only be sought for in the nuclei. Nägeli’s views as to ontogeny can be best seen in the following passages: ‘As soon as ontogenetic development begins, the groups of micellae in the idioplasm which effect the first stage of development, enter upon active growth: such activity causes a passive growth of the other groups, and an increase in the whole idioplasm, perhaps to many times its former bulk. But the intensities of growth in the two series of groups are unequal, and consequently an increasing tension is produced which sooner or later, according to the number, arrangement, and energy of the active groups, necessarily renders the continuation of the process impossible. In consequence of such disturbance to the equilibrium, active growth now takes place in the next group, leading to fresh irritation, and this group then reacts more strongly than all the others upon the tension which first stimulated its activity. These changes are repeated until all the groups are gone through, and the ontogenetic development finally reaches the stage at which propagation takes place, and thus the original stage of the germ is reached.’

Hence, according to Nägeli, the different stages of ontogeny arise out of the activities of different parts of the idioplasm: certain groups of micellae in the idioplasm represent the germs (‘Anlagen’) of certain structures in the organism: when any such germ reacts under stimulation it produces the corresponding structure. It seems to me that this hypothesis bears some resemblance to Darwin’s theory of pangenesis. I think that Nägeli’s preformed germs of structures (‘Anlagen’) and his groups of such germs are highly elaborated equivalents of the gemmules of pangenesis, which, according to Darwin, manifest activity when their turn comes, or, according to Nägeli, when they react under stimulation. When a group of such germs, by their active growth or by their ‘irritation,’ have caused a similar active growth or a similar irritation in the next group, the former may come to rest, or may remain in a state of activity together with its successor, for a longer or shorter period. Its activity may even last for an unlimited time, as is the case in the formation of leafy shoots in many plants.

Here, again, we recognize the fact that Nägeli’s whole hypothesis is intimately connected with the supposition that the entire mass of idioplasm is continuous throughout the organism. Sometimes one part of the idioplasm and sometimes another part is irritated, and then produces the corresponding organ. But if, on the other hand, the idioplasm does not represent a directly continuous mass, but is composed of thousands of single nucleoplasms which only act together through the medium of their cell-bodies, then we must substitute the conception of ‘ontogenetic stages of development of the idioplasm’ for the conception of germs of structure (‘Anlagen’). The different varieties of nucleoplasm which arise during ontogeny represent, as it were, the germs of Nägeli (‘Anlagen’), because, by means of their molecular structure, they create a specific constitution in the cell-bodies over which they have control, and also because they determine the succession of future nuclei and cells.

It is in this sense, and no other, that I can speak of the presence of preformed germs (‘Anlagen’) in the idioplasm. We may suppose that the idioplasm of the first segmentation nucleus is but slightly different from that of the second ontogenetic stage, viz. that of the two following segmentation nuclei. Perhaps only a few groups of micellae have been displaced or somewhat differently arranged. But nevertheless such groups of micellae were not the germs (‘Anlagen’) of a second stage which pre-existed in the first stage, for the two are distinguished by the possession of a different molecular structure. This structure in the second stage, under normal conditions of development, again brings about the change by which the different molecular structure of the third stage is produced, and so on.

It may be argued that von Baer’s well-known and fundamental law of development is opposed to the hypothesis that the idioplasm of successive ontogenetic stages must gradually assume a simpler molecular structure. The organization of the species has, on the whole, increased immensely in complexity during the course of phylogeny: and if the phyletic stages are repeated in the ontogeny, it seems to follow that the structure of the idioplasm must become more complex in the course of ontogeny instead of becoming simpler. But the complexity of the whole organism is not represented in the molecular structure of the idioplasm of any single nucleus, but by that of all the nuclei present at any one time. It is true that the germ-cell, or rather the idioplasm of the germ-nucleus, must gain greater complexity as the organism which arises from it becomes more complex; but the individual nucleoplasms of each ontogenetic stage may become simpler, while the whole mass of idioplasms in the organism (which, taken together, represent the stage in question) does not by any means lose in complexity.

If we must therefore assume that the molecular structure of the nucleoplasm becomes simpler in the course of ontogeny, as the number of structures which it potentially contains become smaller, it follows that the nucleoplasm in the cells of fully differentiated tissues—such as muscle, nerve, sense-organs, or glands—must possess relatively the most simple molecular structure; for it cannot originate any fresh modification of nucleoplasm, but can only continue to produce cells of the same structure, although it does not always retain this power.

We are thus brought back to the fundamental question as to how the germ-cells arise in the organism. Is it possible that the nucleoplasm of the germ-cell, with its immensely complex molecular structure, potentially containing all the specific peculiarities of an individual, can arise from the nucleoplasm of any of the body-cells,—a substance which, as we have just seen, has lost the power of originating any new kind of cell, because of the continual simplification of its structure during development? It seems to me that it would be impossible for the simple nucleoplasm of the somatic cells to thus suddenly acquire the power of originating the most complex nucleoplasm from which alone the entire organism can be built up: I cannot see any evidence for the existence of a force which could effect such a transformation.

This difficulty has already been appreciated by other writers. Nussbaum’s123 theoretical views, which I have already mentioned, also depend upon the hypothesis that cells which have once become differentiated for the performance of special functions cannot be re-transformed into sexual cells: he also concludes that the latter are separated from all other cells at a very early period of embryonic development, before any histological differentiation has taken place. Valaoritis124 has also recognised that the transformation of histologically differentiated cells into sexual cells is impossible. He was led to believe that the sexual cells of Vertebrata arise from the white blood corpuscles, for he looked upon these latter as differentiated to the smallest extent possible. Neither of these views can be maintained. The former, because the sexual cells of all plants and most animals are not, as a matter of fact, separated from the somatic cells at the beginning of ontogeny; the latter, because it is contradicted by the fact that the sexual cells of vertebrates do not arise from blood corpuscles, but from the germinal epithelium. But even if this fact had not been ascertained we should be compelled to reject Valaoritis’ hypothesis on theoretical grounds, for it is an error to assume that white blood corpuscles are undifferentiated, and that their nucleoplasm is similar to the germ-plasm. There is no nucleoplasm like that of the germ-cell in any of the somatic cells, and no one of these latter can be said to be undifferentiated. All somatic cells possess a certain degree of differentiation, which may be rigidly limited to one single direction, or may take place in one of many directions. All these cells are widely different from the egg-cell from which they originated: they are all separated from it by many generations of cells, and this fact implies that their idioplasms possess a widely different structure from the idioplasm, or germ-plasm, of the egg-cell. Even the nuclei of the two first segmentation spheres cannot possess the same idioplasm as that of the first segmentation nucleus, and it is, of course, far less possible for such an idioplasm to be present in the nucleus of any of the later cells of the embryo. The structure of the idioplasm must necessarily become more and more different from that of the first segmentation nucleus, as the development of the embryo proceeds. The idioplasm of the first segmentation nucleus, and of this nucleus alone, is germ-plasm, and possesses a structure such that an entire organism can be produced from it. Many writers appear to consider it a matter of course that any embryonic cell can reproduce the entire organism, if placed under suitable conditions. But, when we carefully look into the subject, we see that such powers are not even possessed by those cells of the embryo which are nearest to the egg-cell—viz. the first two segmentation spheres. We have only to remember the numerous cases in which one of them forms the ectoderm of the animal while the other produces the endoderm, in order to admit the validity of this objection.