Chapter XI: Preface (1)

The ideas developed in this essay were first expressed during the past winter in a lecture delivered to the students of this University (Freiburg), and they were shortly afterwards—in February and the beginning of March—written in their present form. I mention this, because I might otherwise be reproached for a somewhat partial use of the most recent publications on related subjects. Thus I did not receive Oscar Hertwig’s paper—‘Contributions to the Theory of Heredity’ (Zur Theorie der Vererbung), until after I had finished writing my essay, and I could not therefore make as much use of it as I should otherwise have done. Furthermore, the paper by Kölliker on ‘The Significance of the Nucleus in the Phenomena of Heredity’ (Die Bedeutung der Zellkerne für die Vorgänge der Vererbung), did not appear until after the completion of my manuscript. The essential treatment of the subject would not, however, have been altered if I had received the papers at an earlier date, for as far as the most important point—the significance of the nucleus—is concerned, my views are in accordance with those of both the above-named investigators; while the points upon which our views do not coincide had already received attention in the manuscript.

A. W.

Freiburg I. Breisgau,

June 16, 1885.

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CONTINUITY OF THE GERM-PLASM, &c.

CONTENTS.

Introduction 165

I. The Germ-Plasm 174

1. Historical development of the theory as to the 174
localization of the germ-plasm in the nucleus

2. Nägeli’s ‘idioplasm’ is not identical with Weismann’s 180
‘germ-plasm’

3. A retransformation of somatic idioplasm into germ- 183
idioplasm does not take place

4. Confirmation of the theory as to the significance of the 185
nuclear substance afforded by Nussbaum’s and Gruber’s
experiments on regeneration in Infusoria

5. The nucleoplasm changes during ontogeny according to a 186
certain law

6. The identity of the daughter-nuclei produced by indirect 187
nuclear division, as assumed by Strasburger, is not
necessary for my theory

7. The gradual decrease in complexity of the structure of 190
the nucleus during ontogeny

8. Nägeli’s view on the germs (‘Anlagen’) in the idioplasm 192

9. The manner in which germ-cells arise from somatic cells 194

10. ’Embryonic’ cells in the mature organism 196

11. The rule of probability is against a retransformation of 198
somatic idioplasm into germ-plasm

12. The regular cyclical development of the idioplasm 199
founded upon phylogeny by Nägeli

13. It follows from phyletic considerations that the germ- 201
cells have not arisen at the end of ontogeny

14. They originally arose at the beginning of ontogeny, but 202
at a later period the time of their origin was displaced

15. A continuity of the germ-cells does not now exist in 205
most cases

16. But there is a continuity of the germ-plasm 205

17. Strasburger’s objection to my supposition that the germ- 209
plasm passes along distinct routes

18. The cell-body may remain unchanged when the nucleus is 210
changed

19. It is conceivable that all somatic nuclei may contain 211
some germ-plasm

II. The Significance of the Polar Bodies 212

1. The egg-cell contains two kinds of idioplasm; germ-plasm 213
and histogenetic nucleoplasm

2. The expulsion of the polar bodies signifies the removal 214
of the histogenetic nucleoplasm

3. Other theories as to the significance of the polar 214
bodies

4. The modes of occurrence of polar bodies 217

5. Their possible occurrence in male germ-cells 219

6. There are two kinds of nucleoplasm in the male germ- 219
cells

7. Polar bodies in plants 222

8. Morphological origin of polar bodies 223

III. On the Nature of Parthenogenesis 225

1. The phenomena exhibited in the maturation of the egg are 225
identical in parthenogenetic and sexual development

2. The difference between parthenogenetic and sexual cells 226
must be of a quantitative nature

3. The quantity of the germ-plasm determines development 227

4. The expulsion of polar bodies depends upon the 230
antagonism between germ-plasm and ovogenetic nucleoplasm

5. Fertilization does not act dynamically 231

6. An insufficient quantity of germ-plasm arrests 232
development

7. Relation of the nucleus to the cell 234

8. The case of the bee does not constitute any objection to 234
my theory

9. Strasburger’s views upon parthenogenesis 237

10. Parthenogenesis does not depend upon abundant nutrition 239

11. The indirect causes of sexual and parthenogenetic 241
reproduction

12. The direct causes 242

13. Explanation of the formation of nutritive cells 243

14. Identity of the germ-plasm in male and female germ-cells 246

Note 249

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IV.

THE CONTINUITY OF THE GERM-PLASM AS THE
FOUNDATION OF A THEORY OF HEREDITY.

Introduction.

When we see that, in the higher organisms, the smallest structural details, and the most minute peculiarities of bodily and mental disposition, are transmitted from one generation to another; when we find in all species of plants and animals a thousand characteristic peculiarities of structure continued unchanged through long series of generations; when we even see them in many cases unchanged throughout whole geological periods; we very naturally ask for the causes of such a striking phenomenon: and enquire how it is that such facts become possible, how it is that the individual is able to transmit its structural features to its offspring with such precision. And the immediate answer to such a question must be given in the following terms:—‘A single cell out of the millions of diversely differentiated cells which compose the body, becomes specialized as a sexual cell; it is thrown off from the organism and is capable of reproducing all the peculiarities of the parent body, in the new individual which springs from it by cell-division and the complex process of differentiation.’ Then the more precise question follows: ‘How is it that such a single cell can reproduce the _tout ensemble_ of the parent with all the faithfulness of a portrait?’

The answer is extremely difficult; and no one of the many attempts to solve the problem can be looked upon as satisfactory; no one of them can be regarded as even the beginning of a solution or as a secure foundation from which a complete solution may be expected in the future. Neither Häckel’s[94], ‘Perigenesis of the Plastidule,’ nor Darwin’s[95] ‘Pangenesis,’ can be regarded as such a beginning. The former hypothesis does not really treat of that part of the problem which is here placed in the foreground, viz. the explanation of the fact that the tendencies of heredity are present in single cells, but it is rather concerned with the question as to the manner in which it is possible to conceive the transmission of a certain tendency of development into the sexual cell, and ultimately into the organism arising from it. The same may be said of the hypothesis of His[96], who, like Häckel, regards heredity as the transmission of certain kinds of motion. On the other hand, it must be conceded that Darwin’s hypothesis goes to the very root of the question, but he is content to give, as it were, a provisional or purely formal solution, which, as he himself says, does not claim to afford insight into the real phenomena, but only to give us the opportunity of looking at all the facts of heredity from a common standpoint. It has achieved this end, and I believe it has unconsciously done more, in that the thoroughly logical application of its principles has shown that the real causes of heredity cannot lie in the formation of gemmules or in any allied phenomena. The improbabilities to which any such theory would lead are so great that we can affirm with certainty that its details cannot accord with existing facts. Furthermore, Brooks’[97] well-considered and brilliant attempt to modify the theory of Pangenesis, cannot escape the reproach that it is based upon possibilities, which one might certainly describe as improbabilities. But although I am of opinion that the whole foundation of the theory of Pangenesis, however it may be modified, must be abandoned, I think, nevertheless, its author deserves great credit, and that its production has been one of those indirect roads along which science has been compelled to travel in order to arrive at the truth. Pangenesis is a modern revival of the oldest theory of heredity, that of Democritus, according to which the sperm is secreted from all parts of the body of both sexes during copulation, and is animated by a bodily force; according to this theory also, the sperm from each part of the body reproduces the same part[98].

If, according to the received physiological and morphological ideas of the day, it is impossible to imagine that gemmules produced by each cell of the organism are at all times to be found in all parts of the body, and furthermore that these gemmules are collected in the sexual cells, which are then able to again reproduce in a certain order each separate cell of the organism, so that each sexual cell is capable of developing into the likeness of the parent body; if all this is inconceivable, we must enquire for some other way in which we can arrive at a foundation for the true understanding of heredity. My present task is not to deal with the whole question of heredity, but only with the single although fundamental question—‘How is it that a single cell of the body can contain within itself all the hereditary tendencies of the whole organism?’ I am here leaving out of account the further question as to the forces and the mechanism by which these tendencies are developed in the building-up of the organism. On this account I abstain from considering at present the views of Nägeli, for as will be shown later on, they only slightly touch this fundamental question, although they may certainly claim to be of the highest importance with respect to the further question alluded to above.

Now if it is impossible for the germ-cell to be, as it were, an extract of the whole body, and for all the cells of the organism to despatch small particles to the germ-cells, from which the latter derive their power of heredity; then there remain, as it seems to me, only two other possible, physiologically conceivable, theories as to the origin of germ-cells, manifesting such powers as we know they possess. Either the substance of the parent germ-cell is capable of undergoing a series of changes which, after the building-up of a new individual, leads back again to identical germ-cells; or the germ-cells are not derived at all, as far as their essential and characteristic substance is concerned, from the body of the individual, but they are derived directly from the parent germ-cell.

I believe that the latter view is the true one: I have expounded it for a number of years, and have attempted to defend it, and to work out its further details in various publications. I propose to call it the theory of ‘The Continuity of the Germ-plasm,’ for it is founded upon the idea that heredity is brought about by the transference from one generation to another, of a substance with a definite chemical, and above all, molecular constitution. I have called this substance ‘germ-plasm,’ and have assumed that it possesses a highly complex structure, conferring upon it the power of developing into a complex organism. I have attempted to explain heredity by supposing that in each ontogeny, a part of the specific germ-plasm contained in the parent egg-cell is not used up in the construction of the body of the offspring, but is reserved unchanged for the formation of the germ-cells of the following generation.

It is clear that this view of the origin of germ-cells explains the phenomena of heredity very simply, inasmuch as heredity becomes thus a question of growth and of assimilation,—the most fundamental of all vital phenomena. If the germ-cells of successive generations are directly continuous, and thus only form, as it were, different parts of the same substance, it follows that these cells must, or at any rate may, possess the same molecular constitution, and that they would therefore pass through exactly the same stages under certain conditions of development, and would form the same final product. The hypothesis of the continuity of the germ-plasm gives an identical starting-point to each successive generation, and thus explains how it is that an identical product arises from all of them. In other words, the hypothesis explains heredity as part of the underlying problems of assimilation and of the causes which act directly during ontogeny: it therefore builds a foundation from which the explanation of these phenomena can be attempted.

It is true that this theory also meets with difficulties, for it seems to be unable to do justice to a certain class of phenomena, viz. the transmission of so-called acquired characters. I therefore gave immediate and special attention to this point in my first publication on heredity[99], and I believe that I have shown that the hypothesis of the transmission of acquired characters—up to that time generally accepted—is, to say the least, very far from being proved, and that entire classes of facts which have been interpreted under this hypothesis may be quite as well interpreted otherwise, while in many cases they must be explained differently. I have shown that there is no ascertained fact, which, at least up to the present time, remains in irrevocable conflict with the hypothesis of the continuity of the germ-plasm; and I do not know any reason why I should modify this opinion to-day, for I have not heard of any objection which appears to be feasible. E. Roth[100] has objected that in pathology we everywhere meet with the fact that acquired local disease may be transmitted to the offspring as a predisposition; but all such cases are exposed to the serious criticism that the very point that first needs to be placed on a secure footing is incapable of proof, viz. the hypothesis that the causes which in each particular case led to the predisposition, were really acquired. It is not my intention, on the present occasion, to enter fully into the question of acquired characters; I hope to be able to consider the subject in greater detail at a future date. But in the meantime I should wish to point out that we ought, above all, to be clear as to what we really mean by the expression ‘acquired character.’ An organism cannot acquire anything unless it already possesses the predisposition to acquire it: acquired characters are therefore no more than local or sometimes general variations which arise under the stimulus provided by certain external influences. If by the long-continued handling of a rifle, the so-called ‘Exercierknochen’ (a bony growth caused by the pressure of the weapon in drilling) is developed, such a result depends upon the fact that the bone in question, like every other bone, contains within itself a predisposition to react upon certain mechanical stimuli, by growth in a certain direction and to a certain extent. The predisposition towards an ‘Exercierknochen’ is therefore already present, or else the growth could not be formed; and the same reasoning applies to all other ‘acquired characters.’

Nothing can arise in an organism unless the predisposition to it is pre-existent, for every acquired character is simply the reaction of the organism upon a certain stimulus. Hence I should never have thought of asserting that predispositions cannot be transmitted, as E. Roth appears to believe. For instance, I freely admit that the predisposition to an ‘Exercierknochen’ varies, and that a strongly marked predisposition may be transmitted from father to son, in the form of bony tissue with a more susceptible constitution. But I should deny that the son could develope an ‘Exercierknochen’ without having drilled, or that, after having drilled, he could develope it more easily than his father, on account of the drilling through which the latter first acquired it. I believe that this is as impossible as that the leaf of an oak should produce a gall, without having been pierced by a gall-producing insect, as a result of the thousands of antecedent generations of oaks which have been pierced by such insects, and have thus ‘acquired’ the power of producing galls. I am also far from asserting that the germ-plasm—which, as I hold, is transmitted as the basis of heredity from one generation to another—is absolutely unchangeable or totally uninfluenced by forces residing in the organism within which it is transformed into germ-cells. I am also compelled to admit that it is conceivable that organisms may exert a modifying influence upon their germ-cells, and even that such a process is to a certain extent inevitable. The nutrition and growth of the individual must exercise some influence upon its germ-cells; but in the first place this influence must be extremely slight, and in the second place it cannot act in the manner in which it is usually assumed that it takes place. A change of growth at the periphery of an organism, as in the case of an ‘Exercierknochen,’ can never cause such a change in the molecular structure of the germ-plasm as would augment the predisposition to an ‘Exercierknochen,’ so that the son would inherit an increased susceptibility of the bony tissue or even of the particular bone in question. But any change produced will result from the reaction of the germ-cell upon changes of nutrition caused by alteration in growth at the periphery, leading to some change in the size, number, or arrangement of its molecular units. In the present state of our knowledge there is reason for doubting whether such reaction can occur at all; but, if it can take place, at all events the quality of the change in the germ-plasm can have nothing to do with the quality of the acquired character, but only with the way in which the general nutrition is influenced by the latter. In the case of the ‘Exercierknochen’ there would be practically no change in the general nutrition, but if such a bony growth could reach the size of a carcinoma, it is conceivable that a disturbance of the general nutrition of the body might ensue. Certain experiments on plants—in which Nägeli showed that they can be submitted to strongly varied conditions of nutrition for several generations, without the production of any visible hereditary change—show that the influence of nutrition upon the germ-cells must be very slight, and that it may possibly leave the molecular structure of the germ-plasm altogether untouched. This conclusion is also supported by comparing the uncertainty of these results with the remarkable precision with which heredity acts in the case of those characters which are known to be transmitted. In fact, up to the present time, it has never been proved that any changes in general nutrition can modify the molecular structure of the germ-plasm, and far less has it been rendered by any means probable that the germ-cells can be affected by acquired changes which have no influence on general nutrition. If we consider that each so-called predisposition (that is, a power of reacting upon a certain stimulus in a certain way, possessed by any organism or by one of its parts) must be innate, and further that each acquired character is only the predisposed reaction of some part of an organism upon some external influence; then we must admit that only one of the causes which produce any acquired character can be transmitted, the one which was present before the character itself appeared, viz. the predisposition; and we must further admit that the latter arises from the germ, and that it is quite immaterial to the following generation whether such predisposition comes into operation or not. The continuity of the germ-plasm is amply sufficient to account for such a phenomenon, and I do not believe that any objection to my hypothesis, founded upon the actually observed phenomena of heredity, will be found to hold. If it be accepted, many facts will appear in a light different from that which has been cast upon them by the hypothesis which has been hitherto received,—a hypothesis which assumes that the organism produces germ-cells afresh, again and again, and that it produces them entirely from its own substance. Under the former theory the germ-cells are no longer looked upon as the product of the parent’s body, at least as far as their essential part—the specific germ-plasm—is concerned: they are rather considered as something which is to be placed in contrast with the _tout ensemble_ of the cells which make up the parent’s body, and the germ-cells of succeeding generations stand in a similar relation to one another as a series of generations of unicellular organisms, arising by a continued process of cell-division. It is true that in most cases the generations of germ-cells do not arise immediately from one another as complete cells, but only as minute particles of germ-plasm. This latter substance, however, forms the foundation of the germ-cells of the next generation, and stamps them with their specific character. Previous to the publication of my theory, G. Jäger[101], and later M. Nussbaum[102], have expressed ideas upon heredity which come very near to my own[103]. Both of these writers started with the hypothesis that there must be a direct connexion between the germ-cells of succeeding generations, and they tried to establish such a continuity by supposing that the germ-cells of the offspring are separated from the parent germ-cell before the beginning of embryonic development, or at least before any histological differentiation has taken place. In this form their suggestion cannot be maintained, for it is in conflict with numerous facts. A continuity of the germ-_cells_ does not now take place, except in very rare instances; but this fact does not prevent us from adopting a theory of the continuity of the germ-_plasm_, in favour of which much weighty evidence can be brought forward. In the following pages I shall attempt to develope further the theory of which I have just given a short account, to defend it against any objections which have been brought forward, and to draw from it new conclusions which may perhaps enable us more thoroughly to appreciate facts which are known, but imperfectly understood. It seems to me that this theory of the continuity of the germ-plasm deserves at least to be examined in all its details, for it is the simplest theory upon the subject, and the one which is most obviously suggested by the facts of the case, and we shall not be justified in forsaking it for a more complex theory until proof that it can be no longer maintained is forthcoming. It does not presuppose anything except facts which can be observed at any moment, although they may not be understood,—such as assimilation, or the development of like organisms from like germs; while every other theory of heredity is founded on hypotheses which cannot be proved. It is nevertheless possible that continuity of the germ-plasm does not exist in the manner in which I imagine that it takes place, for no one can at present decide whether all the ascertained facts agree with and can be explained by it. Moreover the ceaseless activity of research brings to light new facts every day, and I am far from maintaining that my theory may not be disproved by some of these. But even if it should have to be abandoned at a later period, it seems to me that, at the present time, it is a necessary stage in the advancement of our knowledge, and one which must be brought forward and passed through, whether it prove right or wrong, in the future. In this spirit I offer the following considerations, and it is in this spirit that I should wish them to be received.

I. The Germ-plasm.

I must first define precisely the exact meaning of the term germ-plasm.

In my previous writings in which the subject has been alluded to, I have simply spoken of germ-plasm without indicating more precisely the part of the cell in which we may expect to find this substance—the bearer of the characteristic nature of the species and of the individual. In the first place such a course was sufficient for my immediate purpose, and in the second place the number of ascertained facts appeared to be insufficient to justify a more exact definition. I imagined that the germ-plasm was that part of a germ-cell of which the chemical and physical properties—including the molecular structure—enable the cell to become, under appropriate conditions, a new individual of the same species. I therefore believed it to be some such substance as Nägeli[104], shortly afterwards, called idioplasm, and of which he attempted, in an admirable manner, to give us a clear understanding. Even at that time one might have ventured to suggest that the organized substance of the nucleus is in all probability the bearer of the phenomena of heredity, but it was impossible to speak upon this point with any degree of certainty. O. Hertwig[105] and Fol[106] had shown that the process of fertilization is attended by a conjugation of nuclei, and Hertwig had even then distinctly said that fertilization generally depends upon the fusion of two nuclei; but the possibility of the co-operation of the substance of the two germ-cells could not be excluded, for in all the observed cases the sperm-cell was very small and had the form of a spermatozoon, so that the amount of its cell-body, if there is any, coalescing with the female cell, could not be distinctly seen, nor was it possible to determine the manner in which this coalescence took place. Furthermore, it was for some time very doubtful whether the spermatozoon really contained true nuclear substance, and even in 1879 Fol was forced to the conclusion that these bodies consist of cell-substance alone. In the following year my account of the sperm-cells of _Daphnidae_ followed, and this should have removed every doubt as to the cellular nature of the sperm-cells and as to their possession of an entirely normal nucleus, if only the authorities upon the subject had paid more attention to these statements[107]. In the same year (1880) Balfour summed up the facts in the following manner—‘The act of impregnation may be described as the fusion of the ovum and spermatozoon, and the most important feature in this act appears to be the fusion of a male and female nucleus[108].’ It is true that Calberla had already observed in _Petromyzon_, that the tail of the spermatozoon does not penetrate into the egg, but remains in the micropyle; but on the other hand the head and part of the ‘middle-piece’ which effect fertilization, certainly contain a small fraction of the cell-body in addition to the nuclear substance, and although the amount of the former which thus enters the egg must be very small, it might nevertheless be amply sufficient to transmit the tendencies of heredity. Nägeli and Pflüger rightly asserted, at a later date, that the amount of the substance which forms the basis of heredity is necessarily very small, for the fact that hereditary tendencies are as strong on the paternal as on the maternal side, forces us to assume that the amount of this substance is nearly equal in both male and female germ-cells. Although I had not published anything upon the point, I was myself inclined to ascribe considerable importance to the cell-substance in the process of fertilization; and I had been especially led to adopt this view because my investigations upon _Daphnidae_ had shown that an animal produces large sperm-cells with an immense cell-body whenever the economy of its organism permits. All _Daphnidae_ in which internal fertilization takes place (in which the sperm-cells are directly discharged upon the unfertilized egg), produce a small number of such large sperm-cells (_Sida_, _Polyphemus_, _Bythotrephes_); while all species with external fertilization (_Daphnidae_, _Lynceinae_) produce very small sperm-cells in enormous numbers, thus making up for the immense chances against any single cell being able to reach an egg. Hence the smaller the chances of any single sperm-cell being successful, the larger is the number of such cells produced, and a direct result of this increase in number is a diminution in size. But why should the sperm-cells remain or become so large in the species in which fertilization is internal? The idea suggests itself that the species in this way gains some advantage, which must be given up in the other cases; although such advantage might consist in assisting the development of the fertilized ovum and not in any increase of the true fertilizing substance. At the present time we are indeed disposed to recognize this advantage in still more unimportant matters, but at that time the ascertained facts did not justify us in the assertion that fertilization is a mere fusion of nuclei, and M. Nussbaum[109] quite correctly expressed the state of our knowledge when he said that the act of fertilization consisted in ‘the union of identical parts of two homologous cells.’

Pflüger’s discovery of the ‘isotropism’ of the ovum was the first fact which distinctly pointed to the conclusion that the bodies of the germ-cells have no share in the transmission of hereditary tendencies. He showed that segmentation can be started in different parts of the body of the egg, if the latter be permanently removed from its natural position. This discovery constituted an important proof that the body of the egg consists of a uniform substance, and that certain parts or organs of the embryo cannot be potentially contained in certain parts of the egg, so that they can only arise from these respective parts and from no others. Pflüger was mistaken in the further interpretation, from which he concluded that the fertilized ovum has no essential relation to the organization of the animal subsequently formed by it, and that it is only the recurrence of the same external conditions which causes the germ-cell to develope always in the same manner. The force of gravity was the first factor, which, as Pflüger thought, determined the building up of the embryo: but he overlooked the fact that isotropism can only be referred to the body of the egg, and that besides this cell-body there is also a nucleus present, from which it was at least possible that regulative influences might emanate. Upon this point Born[110] first showed that the position of the nucleus is changed in eggs which are thus placed in unnatural conditions, and he proved that the nucleus must contain a principle which in the first place directs the formation of the embryo. Roux[111] further showed that, even when the effect of gravity is compensated, the development is continued unchanged, and he therefore concluded that the fertilized egg contains within itself all the forces necessary for normal development. Finally, O. Hertwig[112] proved from observations on the eggs of sea-urchins, that at any rate in these animals, gravity has no directive influence upon segmentation, but that the position of the first nuclear spindle decides the direction which will be taken by the first divisional plane of segmentation. These observations were however still insufficient to prove that fertilization is nothing more than the fusion of nuclei[113].

A further and more important step was taken when E. van Beneden[114] observed the process of fertilization in _Ascaris megalocephala_. Like the investigations of Nussbaum[115] upon the same subject, published at a rather earlier date, van Beneden’s observations did not altogether exclude the possibility of the participation of the body of the sperm-cell in the real process of fertilization; still the fact that the nuclei of the egg-cell and the sperm-cell do not coalesce irregularly, but that their loops are placed regularly opposite one another in pairs and thus form one new nucleus (the first segmentation nucleus), distinctly pointed to the conclusion that the nuclear substance is the sole bearer of hereditary tendencies—that in fact fertilization depends upon the coalescence of nuclei. Van Beneden himself did not indeed arrive at these conclusions: he was prepossessed with the idea that fertilization depends upon the union of two sexually differentiated nuclei, or rather half-nuclei—the male and female pronuclei. He considered that only in this way could a single complete nucleus be formed, a nucleus which must of course be hermaphrodite, and he believed that the essential cause of further development lies in the fact that, at each successive division of nuclei and cells, this hermaphrodite nature of the nucleus is maintained by the longitudinal division of the loops of each mother-nucleus, causing a uniform distribution of the male and female loops in both daughter-nuclei.

But van Beneden undoubtedly deserves great credit for having constructed the foundation upon which a scientific theory of heredity could be built. It was only necessary to replace the terms male and female pronuclei, by the terms nuclear substance of the male and female parents, in order to gain a starting-point from which further advance became possible. This step was taken by Strasburger, who at the same time brought forward an instance in which the nucleus only of the male germ-cell (to the exclusion of its cell-body) reaches the egg-cell. He succeeded in explaining the process of fertilization in Phanerogams, which had been for a long time involved in obscurity, for he proved that the nucleus of the sperm-cell (the pollen-tube) enters the embryo-sac and fuses with the nucleus of the egg-cell: at the same time he came to the conclusion that the body of the sperm-cell does not pass into the embryo-sac, so that in this case fertilization can only depend upon the fusion of nuclei[116].

Thus the nuclear substance must be the sole bearer of hereditary tendencies, and the facts ascertained by van Beneden in the case of _Ascaris_ plainly show that the nuclear substance must not only contain the tendencies of growth of the parents, but also those of a very large number of ancestors. Each of the two nuclei which unite in fertilization must contain the germ-nucleoplasm of both parents, and this latter nucleoplasm once contained and still contains the germ-nucleoplasm of the grandparents as well as that of all previous generations. It is obvious that the nucleoplasm of each antecedent generation must be represented in any germ-nucleus in an amount which becomes less as the number of intervening generations becomes greater; and the proportion can be calculated after the manner in which breeders, when crossing races, determine the proportion of pure blood which is contained in any of the descendants. Thus while the germ-plasm of the father or mother constitutes half the nucleus of any fertilized ovum, that of a grandparent only forms a quarter, and that of the tenth generation backwards only 1/1024, and so on. The latter can, nevertheless, exercise influence over the development of the offspring, for the phenomena of atavism show that the germ-plasm of very remote ancestors can occasionally make itself felt, in the sudden reappearance of long-lost characters. Although we are unable to give a detailed account of the way in which atavism happens, and of the circumstances under which it takes place, we are at least able to understand how it becomes possible; for even a very minute trace of a specific germ-plasm possesses the definite tendency to build up a certain organism, and will develope this tendency as soon as its nutrition is, for some reason, favoured above that of the other kinds of germ-plasm present in the nucleus. Under these circumstances it will increase more rapidly than the other kinds, and it is readily conceivable that a preponderance in the quantity of one kind of nucleoplasm may determine its influence upon the cell-body.

Strasburger—supported by van Beneden’s observations, but in opposition to the opinions of the latter—had already explained, in a manner similar to that described above, the process by which the hereditary transmission of certain characters takes place, and to this extent our opinions coincide. The nature of heredity is based upon the transmission of nuclear substance with a specific molecular constitution. This substance is the specific nucleoplasm of the germ-cell, to which I have given the name of germ-plasm.

O. Hertwig[117] has also come to the same conclusion: at an earlier date he had looked upon the coalescence of nuclei as the most essential feature in the process of fertilization. He now believes that this former opinion has been confirmed by the recent discoveries which have been shortly described above.

Although I entirely agree with Hertwig, as far as the main question is concerned, I cannot share his opinions when he identifies Nägeli’s idioplasm with the nucleoplasm of the germ-cell. Nägeli’s idioplasm certainly includes the germ-plasm, if I may retain this expression for the sake of brevity. Nägeli in forming his hypothesis did indeed start with the germ-cells, but his idioplasm not only represents the nucleoplasm of the germ-cells, but also that of all the other cells of the organism; all these nucleoplasms taken together constitute Nägeli’s idioplasm. According to Nägeli, the idioplasm forms a network which extends through the whole body, and represents the specific molecular basis which determines its nature. Although this latter suggestion—the general part of his theory—is certainly valid, and although it is of great importance to have originated the idea of idioplasm in this general sense, in contrast to the somato-plasm (‘Nährplasma’), it is nevertheless true that we are not justified in retaining the details of his theory.

In the first place the idioplasm does not form a directly continuous network throughout the entire body; and, secondly, the whole organism is not penetrated by a single substance of homogeneous constitution, but each special kind of cell must contain the specific idioplasm or nucleoplasm which determines its nature. There are therefore in each organism a multitude of different kinds of idioplasm. Thus we should be quite justified in generally speaking of Nägeli’s idioplasm as nucleoplasm, and _vice versa_.

It is perfectly certain that the idioplasm cannot form a continuous network through the whole organism, if it is seated in the nucleus and not in the cell-body. Even if the bodies of cells are everywhere connected by fine processes (as has been proved in animals by Leydig and Heitzmann, and in plants by various botanists), they do not form a network of idioplasm but of somato-plasm; a substance which, according to Nägeli, stands in marked contrast to idioplasm. Strasburger has indeed already spoken of a ‘cyto-idioplasm,’ and it is certainly obvious that the cell-body often possesses a specific character, but we must in all cases assume that such a character is impressed upon it by the influence of the nucleus, or, in other words, that the direction in which the cell-substance is differentiated in the course of development is determined by the quality of its nuclear substance. So far, therefore, the determining nuclear substance corresponds to the idioplasm alone, while the substance of the cell-body must be identified with the somato-plasm (‘Nährplasma’) of Nägeli. At all events, in practice, it will be well to restrict the term idioplasm to the regulative nuclear substance alone, if we desire to retain the well-chosen terms of Nägeli’s theory.

But the second part of Nägeli’s theory of the idioplasm is also untenable. It is impossible that this substance can have the same constitution everywhere in the organism and during every stage of its ontogeny. If this were so, how could the idioplasm effect the great differences which obtain in the formation of the various parts of the organism? In some passages of his work Nägeli seems to express the same opinion; e. g. on page 31 he says, ‘It would be practicable to regard—although only in a metaphorical sense—the idioplasms of the different cells of an individual as themselves different, inasmuch as they possess specific powers of production: we should thus include among these idioplasms all the conditions of the organism which bring about the display of specific activity on the part of cells.’ It can be clearly seen from the passages immediately preceding and succeeding the above-quoted sentence, that Nägeli, in speaking of these changes in the idioplasm, does not refer to material, but only to dynamical changes. On page 53 he lays special stress upon the statement that ‘the idioplasm during its growth retains its specific constitution everywhere throughout the organism,’ and it is only ‘within these fixed structural limits that it changes its conditions of tension and movement, and thus alters the forms of growth and activity which are possible at each time and place.’ Against such an interpretation weighty objections can be raised. At present I will only mention that the meaning of the phrase ‘conditions of tension and movement’ ought to be made clear, and that we ought to be informed how it is that mere differences in tension can produce as many different effects as could have been produced by differences of constitution. If any one were to assert that in _Daphnidae_, or in any other forms which produce two kinds of eggs, the power of developing only after a period of rest, possessed by the winter-eggs, is based upon the fact that their idioplasm is identical with that of the summer-eggs, but is in another condition of tension, I should think such a hypothesis would be well worth consideration, for the animals which arise from the winter-eggs are identical with those produced in summer: the idioplasm which caused their formation must therefore be identical in its constitution; and can only differ in the two cases, as water differs from ice. But the case is quite otherwise in the stages of ontogeny. How many different conditions of tension ought to be possessed by one and the same idioplasm in order to correspond to the thousand different structures and differentiations of cells in one of the higher organisms? In fact it would be hardly possible to form even an approximate conception of an explanation based upon mere ‘conditions of tensions and movement.’ But, furthermore, difference in effect should correspond, at any rate to some extent, with difference in cause: thus the idioplasm of a muscle-cell ought to differ more from that of a nerve-cell and of a digestive-cell in the same individual, than the idioplasm of the germ-cell of one individual differs from that of other individuals of the same species; and yet, according to Nägeli, the latter small difference in the effect is supposed to be due to difference of quality in the cause—the idioplasm, while the former fundamental difference in the histological differentiation of cells is supposed to follow from mere difference ‘of tension and movement.’

Nägeli’s hypothesis appears to be self-contradictory; for, although its author recognizes the truth of the fundamental law of development, and explains the stages of ontogeny as an abbreviated recapitulation of phyletic stages, he nevertheless explains the latter by a different principle from that which he employs to explain the former. According to Nägeli, the stages of phylogeny are based upon true qualitative differences in the idioplasm: the germ-plasm of a worm is qualitatively different from that of _Amphioxus_, a frog, or a mammal. But if such phyletic stages occur crowded together in the ontogeny of a single species, they are said to be based upon different ‘conditions of tension and movement’ of one and the same idioplasm! It seems to me to be necessary to conclude that if the idioplasm, in the course of phyletic development, undergoes any alteration in specific constitution, such alterations must also take place in ontogeny; so far at least as the phyletic stages are repeated. Either the whole phyletic development is based upon different ‘conditions of tension and movement,’ or if this—as I believe—is impossible, the stages of ontogeny must be based upon qualitative alterations in the idioplasm.

Involuntarily the question arises—how is it that such an acute thinker fails to perceive this contradiction? But the answer is not far to seek, and Nägeli himself indicates it when he adds these words to the sentence quoted above: ‘It follows therefore that if a cell is detached as a germ-cell in any stage of ontogenetic development, and from any part of the organism, such a cell will contain all the hereditary tendencies of the parent individual.’ In other words, if we are restricted to different ‘conditions of tension and movement’ as an explanation, it seems to follow as a matter of course that the idioplasm can re-assume its original condition, and therefore that the idioplasm of any cell in the body can again become the idioplasm of the germ-cell; for this to take place it is only necessary that the greater tension should become the less, or _vice versa_. But if we admit a real change in constitution, then the backward development of the idioplasm of the cells of the body into germ-cells appears to be very far from a matter of course, and he who assumes it must bring forward weighty reasons. Nägeli does not produce such reasons, but considers the metamorphosis of the idioplasm in ontogeny as mere differences in the ‘conditions of tension and movement.’ This phrase covers the weak part of his theory; and I look upon it as a valuable proof that Nägeli has also felt that the phenomena of heredity can only find their explanation in the hypothesis of the continuity of the germ-plasm; for his phrase is only capable of obscuring the question as to how the idioplasm of the cells of the body can be re-transformed into the idioplasm of germ-cells.

I am of the opinion that the idioplasm cannot be re-transformed, and I have defended this opinion for some years past[118], although I have hitherto laid especial stress on the positive aspect of the question, viz. on the continuity of the germ-plasm. I have attempted to prove that the germ-cells of an organism derive their essential nature from the fact that the germ-plasm of each generation is carried over into that which succeeds it; and I have tried to show that during the development of an egg into an animal, a part of the germ-substance—although only a minute part—passes over unchanged into the organism which is undergoing development, and that this part represents the basis from which future germ-cells arise. In this way it is to a certain extent possible to conceive how it is that the complex molecular structure of the germ-plasm can be retained unchanged, even in its most minute details, through a long series of generations.

But how would this be possible if the germ-plasm were formed anew in each individual by the transformation of somatic idioplasm? And yet if we reject the ‘continuity of the germ-plasm’ we are compelled to adopt this latter hypothesis concerning its origin. It is the hypothesis adopted by Strasburger, and we have therefore to consider how the subject presents itself from his point of view.

I entirely agree with Strasburger when he says, ‘The specific qualities of organisms are based upon nuclei’; and I further agree with him in many of his ideas as to the relation between the nucleus and cell-body: ‘Molecular stimuli proceed from the nucleus into the surrounding cytoplasm; stimuli which, on the one hand, control the phenomena of assimilation in the cell, and, on the other hand, give to the growth of the cytoplasm, which depends upon nutrition, a certain character peculiar to the species.’ ‘The nutritive cytoplasm assimilates, while the nucleus controls the assimilation, and hence the substances assimilated possess a certain constitution and nourish in a certain manner the cyto-idioplasm and the nuclear idioplasm. In this way the cytoplasm takes part in the phenomena of construction, upon which the specific form of the organism depends. This constructive activity of the cyto-idioplasm depends upon the regulative influence of the nuclei.’ The nuclei therefore ‘determine the specific direction in which an organism developes.’

The opinion—derived from the recent study of the phenomena of fertilization—that the nucleus impresses its specific character upon the cell, has received conclusive and important confirmation in the experiments upon the regeneration of Infusoria, conducted simultaneously by M. Nussbaum[119] at Bonn, and by A. Gruber[120] at Freiburg. Nussbaum’s statement that an artificially separated portion of a _Paramaecium_, which does not contain any nuclear substance, immediately dies, must not be accepted as of general application, for Gruber has kept similar fragments of other Infusoria alive for several days. Moreover, Gruber had previously shown that individual Protozoa occur, which live in a normal manner, and are yet without a nucleus, although this structure is present in other individuals of the same species. But the meaning of the nucleus is made clear by the fact, published by Gruber, that such artificially separated fragments of Infusoria are incapable of regeneration, while on the other hand those fragments which contain nuclei always regenerate. It is therefore only under the influence of the nucleus that the cell substance re-developes into the full type of the species. In adopting the view that the nucleus is the factor which determines the specific nature of the cell, we stand on a firm foundation upon which we can build with security.

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.