Chapter I: NOW turn to the consideration of the process of fertilization in (2)

It is only from the standpoint of utility that we can understand the occurrence of natural death; we see that the germ-cells _must_ be potentially immortal like the unicellular organisms, but that the cells which make up the tissues of the body _may_ be transient, and indeed _must_ be so in the interests of their differentiation--often great and in one direction--which determines the services they render to the body. They required to become so differentiated that they could not continue to live on without limit, and they did become so differentiated because only thus could an ever-increasing functional capacity of the whole organism be rendered possible; but they die not because 'rejuvenescence through amphimixis is denied them, but because their physical constitution is what it is.' And we must explain the death of the whole many-celled individual in a similar way. When we were trying in a previous study to establish the unlimited continuance, the potential immortality, of unicellular organisms, we noted that an eternal continuance of the life of the body of multicellular organisms could certainly not be a necessity, since the continuance of these forms of life is secured by their germ-cells. A continuance of the body cannot even be regarded as useful from any point of view. And what is not useful for a form of life _does not arise as a lasting adaptation_, which is of course not to say that an immortality of multicellular organisms, such as they are now, would even have been possible. If these organisms were to attain to such a high degree of functional capacity and of structural complexity as they now exhibit, they obviously could not also have been adapted at the same time to an eternal persistence of life.

This is in perfect harmony with our whole conception of the impelling forces in the development of the organic world; the ever-increasing functional capacity of the structure arose from the advantage which this afforded in the struggle for existence, in comparison with which the apparent advantage of the endless life of the individual was of no account whatever.

I will not here follow out this idea. I have merely touched on it in order to make clear that the death of individuals in all multicellular organisms gives us no ground for thinking of the unlimited life of the germ-cells as dependent on a special artifice of nature, such as amphimixis is often supposed to be. Let us always remember that there is parthenogenesis, and that there are unicellular germs (spores) which are never fertilized, and that the reproduction of many species of animals and plants occurs in this way without the intervention of amphimixis at all.

* * * * *

Attempts have recently been made to prove that parthenogenesis is a kind of self-fertilization, and these have been based on the observations of Blochmann and Brauer, which showed that in the bee and in the salt-water Crustacean, _Artemia salina_, the reducing second maturation division of the ovum-nucleus is not suppressed, but is regularly accomplished, and that the two daughter-nuclei which result from this division unite with each other subsequently. I have already noted that these statements do not hold true, at least with regard to the bee. In this case the second maturing division takes place without any subsequent fusion of the two daughter-nuclei. According to the observations of Dr. Petrunkewitsch, which I have already mentioned, and for the exactness of which I can vouch, the second maturation-spindle is unusually long, so that the two daughter-nuclei are pushed very far apart (Fig. 79, _Rsp 2_), and only the inner of the two nuclei (_K 4_) becomes a segmentation nucleus, while the outer undergoes a remarkable fate; it unites with the inner nucleus which results from the division of the _first maturation cell_ (_K 2_), and from this union the primitive _genital cells of the animal appear to arise_--an observation the eventual theoretical importance of which can only be estimated later.

Meantime all we can gain from it is a certain mistrust of the interpretation of the processes of maturation in _Artemia_ which have hitherto been given; at least we are tempted to suppose that the copulation of two nuclei which Brauer observed in _Artemia_ may not have led to the formation of the segmentation nucleus there either, but may have had some other significance.

But, even if we leave this point entirely out of account, there remain all the cases of regular parthenogenesis in which this mode of reproduction occurs alone and not in alternation with the sexual mode. In these only one maturing division is undergone, and only one polar body is formed, and thus there can lie no possibility of supposing a self-fertilization of the ovum.

It is possible that we may yet discover species among unicellular organisms which multiply without limit in the absence of any amphimixis. R. Hertwig has recently observed phenomena in Infusorians which he is inclined to refer to the suppression of an earlier habit of conjugation, and so to a kind of parthenogenesis. But even if it should be shown that amphimixis plays a part regularly and without exception in the life of _all_ unicellular organisms, the facts in regard to multicellular organisms are not affected; and, finally, the process of amphimixis is one which we have not the slightest ground for assuming to be either an awakener or a maintainer of life, and so I return to the most essential part of the whole problem, the meaning of the chromatin structures, the combination of which is the undoubted result of amphimixis. Do they really represent, as we assumed earlier, _the hereditary substance_, and what do we mean by this term?

As far as I know the literature and the development of biological theories, the botanist Nägeli was the first to deduce, from the considerable difference in size between the egg-cell and the sperm-cell, the conclusion that the material basis on which the hereditary tendencies depend must be a _minimal_ quantity of substance. The difference is especially great in animals, even in those species whose eggs may be called small, for instance, those of sea-urchins or of mammals; even in these the mass of spermatozoon is scarcely a thousandth part, often scarcely a hundred-thousandth part of the mass of the ovum. And yet the inheritance from the father and from the mother is equally great. Now as we know that vital powers have always a material basis, a minute quantity, such as is contained, for instance, in the spermatozoon of Man, must have implicitly in it all the hereditary tendencies of the father; and the conclusion is inevitable that in the ovum there can only be an equally minimal quantity of substance which is the bearer of the hereditary powers, for if there were a larger quantity of hereditary substance in the ovum its power of transmission would also be greater[16].

[16] The improbable assumption that the hereditary substance of the father may be in quality altogether different from that of the mother, and so may have the same power of transmission, and yet take up much less room, I leave out of the question altogether.

If we inquire as to the part of the spermatozoon which bears this hereditary substance, we may exclude both the tail-thread and the middle piece (Fig. 68), the former because it obviously fulfils quite a specialized physiological function and is histologically adapted to this function, the latter because, from observation on the spermatozoon which has made its way into the ovum, we know that it contains the centrosome, the dividing apparatus of the nucleus. Thus there only remains the 'head' of the spermatozoon, which includes the nucleus, as the possible vehicle of the heritable substance. Therefore we are led to seek for the hereditary substance in the nucleus. But the hereditary substance cannot be a perishable substance which may at need be dissolved, in the literal sense of the word, and be formed anew; therefore we cannot look for it in the nuclear membrane, and just as little in the 'nuclear sap' which fills the meshes of the nuclear network, since the material on which heredity depends must necessarily be solid. Nägeli has clearly shown that we must assume a stable, that is, a solid molecular architecture. There thus remains only the nuclear reticulum with its chromatin granules, and when we remember what we have learnt of the behaviour of this chromatin substance during division and amphimixis we can entertain no doubt that the sought-for bearer of the inheritance is contained in the substance of the chromosomes.

The great care with which the chromosomes are halved by means of the complicated division apparatus led us earlier to regard them as a substance of complex and manifold qualities and of great physiological importance; their constant number in any one species, and the reduction of that number to half by means of the reducing divisions, justify us in concluding that they are permanent structures, physiological and morphological units, which undergo no more than an apparent irregular dispersion during the resting state of the nucleus. Finally, the fact that these supposed vehicles of inheritance occur in equal numbers in each of the conjugating germ-cells, and that this number is _always_, both in animals and in plants, half of the normal number occurring in somatic cells, is decisive. The logical necessity that the hereditary substance of both parents should be transmitted to the offspring in equal quantity could not be more precisely met than it is by the fact that half the normal number of chromosomes occurs in each of the sex-nuclei in the ovum. Personally, I have long been certain, on these grounds, that the chromosomes of the nucleus are the hereditary substance, and I expressed my conviction on this point almost simultaneously with Strasburger and O. Hertwig[17].

[17] More precisely, my conclusions were published several months later than those of the investigators named (1885). I think, however, that no one who is familiar with my writings for the years immediately preceding, which are collected in _Aufsätzen über Vererbung und verwandte biologische Fragen_ (Jena, 1892), will dispute that the idea was reached by me independently. I attach importance to this because all my later work is based upon this idea.

But there is also a physiological proof of the meaning of the nuclear substance; and this we owe, again, to the simultaneous and independent researches of two investigators, M. Nussbaum and A. Gruber, the latter working in the Zoological Institute here (in Freiburg), and at my request. They made experiments on regeneration in unicellular organisms, and found that Infusorians which were artificially divided into two, three, or four pieces were able to build up a whole animal out of each piece, provided that it contained a portion of the nucleus (macronucleus). The large blue trumpet-animalcule, _Stentor cœruleus_, is well suited for such experiments, not only on account of its size, but because it possesses a very long rosary-like nucleus, which can be easily cut two or three times. When a piece is cut off which does not contain a portion of the nucleus, it may indeed live for some days and swim about and contract, but it is incapable of reconstructing the lost parts, and thus of forming a whole animal, and it perishes. It is in the nucleus, therefore, that we have to look for the substance which stamps the material of the cell-body with a particular form and organization, namely, the form and organization of its ancestors. But that is exactly the conception of a hereditary substance or idioplasm (Nägeli). Some modern biologists deny that there is any hereditary substance _per se_, and believe that the whole of the germ-cell, cell-body and nucleus together effects transmission. But though it must be admitted that the nucleus without the cell-body cannot express inheritance any more than the cell-body without the nucleus, this is dependent on the fact that the nucleus cannot live without the cell-body; if it be removed from the cell and put, say, into water, it bursts and is dissolved. But the cell-body without the nucleus lives on, though of course only for a few hours or days, and its metabolism ceases only when it is brought to a standstill by the failure to replace by nutrition the used-up material. Thus the argument used by those who deny the existence of a hereditary substance would be paralleled if we denied that Man possesses a thinking substance, and maintained that he thinks with his whole body, and even that the brain cannot think by itself without the body.

I am convinced that it is just as mistaken to maintain that every part of an organism must contain the hereditary tendencies in the same degree, or that in unicellular organisms the cell-body is as important in inheritance as the nucleus (Conklin). If one feels any doubt on this point, one has only to call to mind Nägeli's inference, from the minuteness of the spermatozoon, that the hereditary substance must be minimal in quantity. But even theoretically there is not the smallest ground for the assumption that the cell-body as well as the nucleus contains the hereditary qualities, since we find in general that functions are distributed among definite substances and parts of the whole organism, and it is just on this division of labour that the whole differentiation of the body depends. And why should this principle not have been employed just here where the most important of all functions is concerned? Why should all living substance be hereditary substance? Although Nägeli thought of his 'idioplasm' otherwise than we now think of hereditary substance, although he wrongly imagined it in the form of strands running a parallel course through the cell-substance and forming a connected reticulum throughout the whole body, he recognized at least so much quite correctly, that there are two great categories of living substance--hereditary substance or idioplasm, and 'nutritive substance' or trophoplasm, and that the former is much smaller in mass than the latter. We now add to this, that the idioplasm must be sought for in the cell-nucleus, and indeed in the chromatin granules of the nuclear network and of the chromosomes.

But incontrovertible proof of the fact that the nuclear substance _alone_ is the hereditary substance was furnished when it was found possible to introduce into a non-nucleated piece of a mature ovum of one species the nucleus of another related species, and when it was seen that the larva that developed from the ovum so treated belonged to the _second_ species. Boveri made this experiment with the ovum and spermatozoon of two species of sea-urchin, and believed that he had succeeded in getting from non-nucleated pieces of the ovum of the first species, fertilized with the sperm of the second, larvæ of this second species; but, unfortunately, later control-experiments made by several investigators, especially by Seeliger, have shown that this result cannot be regarded as quite certain and indubitable.

I must emphasize again that I am far from regarding the cell-protoplasm of the ovum as an indifferent substance. It is certainly not only important but indispensable for the development of the embryo, and it has assuredly its own specific character, as in every other kind of cell. It represents, so to speak, the matrix and nutritive environment in which alone the hereditary substance can unfold its wonderful powers; it has developed historically, like every other kind of cell, but it contains nothing more than the inherited qualities of this one kind of cell-protoplasm, not those of the other cells of the body.

But although the essence of fertilization lies, as we have seen, in the union of the hereditary substance of two individuals, and not in a 'quickening' of the ovum, we may quite well speak of a quickening by fertilization in another sense, if we mean the impulse to embryonic development, for this is really supplied by the entrance of the sperm-nucleus with its centrosphere into the ovum. But even this impulse can, under certain circumstances, be given in another way, and certainly the awakening of it is not the _end_ of fertilization, but only the condition without which the end, the union of two kinds of nuclear substance, could not be attained. There is no indication whatever that this 'quickening' of the ovum would be necessary for any other reason except that _the ovum was previously made incapable of development_. There would be no 'fertilization' were not the mingling of hereditary substances of fundamental importance for the organic world.

Moreover, an ovum, or a fragment of an ovum, may also develop of itself, having only _one_ of the sex-nuclei, and the union of the hereditary substance of two cells is therefore not indispensable for the mere production of a new individual.

What has been observed in regard to fragments of ova is particularly interesting in this connexion. Ernst Ziegler first succeeded in halving a newly fertilized sea-urchin ovum, so that one half contained the female and the other the male pronucleus. The latter alone contained a centrosphere, and developed a blastula larva. Delage carried these experiments further, and cut an unfertilized but mature sea-urchin ovum into pieces, and then 'fertilized' the non-nucleated pieces with spermatozoa. These pieces developed and yielded young larvæ of the relevant species; so it is clearly seen that even a piece of mature ovum-protoplasm may undergo embryonic development, provided that a nucleus furnished with a dividing apparatus penetrates into it. Unfortunately it is technically impossible to cut such a non-nucleated and then fertilized fragment of ovum so that one half shall contain the male nucleus the other its centrosphere. Even without this _experimentum crucis_ we may say that the half with the male nucleus would not multiply by division, and that the other probably would, though it would not go through the regular course of segmentation processes, because the hereditary substance absolutely necessary for these was wanting.

But these and similar experiments prove something more, namely, that the nuclei of the sperm-cell and egg-cell do not, as was formerly believed, stand in a primary and essential contrast to each other, which may be described as male and female, but that both are alike in their deeper essence, and may replace each other. They only differ from each other as far as the cells to which they belong differ, in this, namely, that they are mutually attractive; they find each other and unite, and then go on to develop, which each was previously unable to do by itself. Widely as the sperm-cell and egg-cell differ in size, constitution, and behaviour, in regard to essential character they are alike; they bear the relation--as I expressed it twenty years ago--of 1:1; that is, _they both contain an equal quantity of essentially similar hereditary substance_, and the quality of this substance is only individually variable. We should, therefore, speak not of a 'male' and 'female,' but of a 'paternal' and a 'maternal' nucleus.

All the more recent experiments on 'merogony,' that is, on the development of fragments of the ovum, confirm this view. Thus Boveri had already observed that even small pieces of sea-urchin ova which did not contain the nucleus of the ovum developed, after the spermatozoon had entered them, into small but otherwise normal larvæ of the species. More recently Hans Winkler proved the same thing for the ova of plants, by dividing the ovum of a marine alga (_Cystosira_) into two pieces, then fertilizing these with water containing sperms, with the result that he got from both pieces, the nucleated and the non-nucleated, an embryo of normal appearance. In the latter it could only have been a 'paternal' nucleus which directed the development.

To sum up. Our investigation into the meaning of amphimixis has led us to the conclusion that it consists in the union of two equal complements of hereditary substance, contributed by two different individuals, into one unified nucleus, and that the sole immediate result of this is _the combination of the hereditary tendencies of two individuals in one_. Among multicellular organisms this one individual of dual origin always implies the beginning of a new life, since amphimixis is indissolubly associated with reproduction, and even among unicellular organisms it can hardly be disputed that the two Infusorians which separate after conjugation are no longer the same as they were before. After amphimixis they must contain a different combination of hereditary substance from what they had before, and this must reproduce the parts of the animal in a somewhat modified form. This is theoretically beyond doubt, although it can scarcely be established by observation.

We thus know now what 'fertilization' is. Through the labours of the last decade the veil has been torn from a mystery of nature which for thousands of years confronted humanity as unapproachable; a riddle has been solved for the solution of which a few centuries ago men did not even dare to hope. Not a few have taken part in these labours; some I have already named, but it is impossible that I should here mention all who have shared in the achievement by observation or reflection. Whoever has helped it on even a single step may say to himself that he has taken an active part in bringing about what must be called essential progress in human knowledge.

But in the science of nature every new solution implies the cropping up of a new riddle, and we are immediately confronted with the problem, Why should nature, in the course of evolution, have interpolated this process of the mingling of different hereditary substances almost everywhere in the organic world? This, however, is a problem which we cannot attack until we have first made ourselves more fully acquainted with the phenomena of inheritance, and have attempted to reason back from these to the nature of the hereditary substance. We must, in short, think out a theory of heredity.

LECTURE XVII

THE GERM-PLASM THEORY

Conception of the 'id' deduced from the process of fertilization--Hereditary substance, 'idioplasm' and 'germ-plasm'--'Idants'--Evolution or Epigenesis--Herbert Spencer's uniform germinal substance--Determinants--Illustrations: _Lycæna agestis_--The leaf-butterflies--Insect metamorphosis, limbs of segmented animals--Heterotopia--The ultimate living units or biophors--Number of determinants--Stridulating organ of the grasshopper.

IN proceeding to expound the theory of heredity which has shaped itself in my mind in the course of my own scientific development, I should like to begin by pointing out that the hereditary substance of the germ-cell of an animal or of a plant contains not only the primary constituents (_Anlagen_) of a single individual of the species, but rather those of several, often even of many individuals. That this is so can be proved in several ways.

I start from what I hold to be the proved proposition, that the chromatin substance of the nucleus is the hereditary substance. We have seen that this is present in the germ-cells of every species in the form of a definite number of chromosomes, and that in germ-cells destined for fertilization, that is, in sex-cells, this number is first reduced to half, the reduction being effected, as is now proved in regard to a whole series of animals, by the two last cell-divisions, the so-called maturation divisions.

We know that the full number is only reached again through amphimixis, by which process the half number of chromosomes in the male and female germ-cells are united in a single cell, the 'fertilized ovum,' and in a single nucleus, the so-called segmentation nucleus. Thus the hereditary substance of the child is formed half from the paternal, half from the maternal hereditary substance, and we have seen that this remains so during the whole development of the child, since, at every succeeding cell-division each of the paternal and each of the maternal chromosomes doubles by dividing, and the resulting halves are distributed between the two daughter-nuclei.

Now if the complete hereditary substance of a germ-cell before the reducing divisions contains potentially all the primary constituents of the body, which it does as a matter of course, then it follows that after the reduction each germ-cell must either contain only half the primary constituents of the parents or all the primary constituents must be contained in the half number of chromosomes. The latter seems to me the only possible assumption, as I shall immediately proceed to show, and this is as much as to say that the primary constituents of at least two complete individuals must be contained in the chromosomes of the segmentation nucleus.

That this conclusion is correct is obvious from the fact that a whole, that is, a perfect individual with all its parts, develops from the ovum, and not a defective one. For suppose that each mature germ-cell contained only half the primary constituents of the body, it would be impossible that these halves should always exactly complete themselves to form a whole embryo when they are brought together in fertilization, after having been halved by mere chance during the preceding reducing division; it would be much more likely to happen that they did not complete themselves, and that their union would therefore result in an individual with certain parts wanting. If, for instance, in the sperm-cell only the anterior half of the body was potentially present, and this united with an ovum which likewise contained only the primary constituents of the anterior half, the embryo resulting from their union would lack the posterior half of the body, and so on. Of course so rough a division of the primary constituents is not to be thought of, but however fine we can imagine the halving of the mass of primary constituents to be, there would never be any guarantee that the two cells uniting in amphimixis would complete the mass of primary constituents again; indeed, the chance that the two exactly complementary halves of the mass would meet would rather become less the finer and more complex one imagines the halving by reducing divisions to be. A perfect embryo with all its parts would rarely arise, but now one group of parts, now another would be wanting, while another group might be developed double, or at least would be doubly present in the primary constituents.

But in addition to this the facts of inheritance show us that the resemblance to mother and father may express itself simultaneously in all the parts, or at least in the same parts of the child, as may be seen with especial clearness among plant-hybrids, and thus the conclusion is inevitable that even in the half number of chromosomes all the primary constituents of the whole body are present.

Let us go a generation further. If the species possess four chromosomes the child will have in its cells two maternal chromosomes (_A_) and two paternal chromosomes (_B_); what form will this proportion take in the germ-cells produced by the child? The maturation division can effect the reduction to two chromosomes in different ways; there may, for instance, be two paternal chromosomes (_B_) left in the one, and two maternal chromosomes (_A_) in the other daughter-cell, or one paternal (_B_) and one maternal (_A_) in the one, and a similar combination in the other cell. Let us follow the latter case further. A sperm-cell which contained the combination _A_ and _B_ might meet in amphimixis with an egg-cell of different origin also containing a similar combination of chromosomes, let us say a chromosome _C_ from the mother, and a chromosome _D_ from the father. We should then have in the segmentation nucleus of the fertilized ovum four different chromosomes, each of which contained the hereditary substance of one grandparent; we should have the four chromosomes, _A_, _B_, _C_, _D_, as the hereditary substance of the grandchild.

_But since, as we have seen, the halved hereditary substance still contains the whole mass of primary constituents, each one of these chromosomes must contain the collective primary constituents of the whole body of the relevant grandparent_[18]. _The hereditary substance in the fertilized ovum thus consists of several complexes of primary constituents (chromosomes) each of which (an 'id') comprises within itself all the primary constituents of a complete individual._

[18] When I say the 'collective' primary constituents of the whole body of the grandparent this is not expressing it quite precisely, for, as we shall see later, each individual must arise from the co-operation of different chromosomes of different origin, not merely from one of the chromosomes contained in its germ-plasm. In the example given above, the body of each grandparent cannot have arisen only from a single chromosome, which was transmitted to his grandchild, but from the co-operation of this chromosome with three others, which have distributed themselves along other genealogical paths. But this does not affect the above chain of reasoning, for here it is not a question of whether all the primary constituents of the grandparent are present in the child--that can never be the case--but whether the primary constituents transmitted by him represent the whole body of an individual.

It can be made clear in yet another way that, as a consequence of sexual reproduction, the germ-plasm of each species must be composed of several 'ids,' _individually different_. Let us assume that there was as yet no amphimixis, and that we could look on at its introduction into the organic world; the hereditary substance of the beings which had previously lived and multiplied by division would consist of more or less numerous chromosomes similar to each other, so that, for instance, each individual would contain sixteen identical 'ids.' But if amphimixis were now to take place for the first time, in the same manner as it does to-day--that is, after the reduction of the number of the ids to half--in the first amphimixis eight paternal ids would unite with eight maternal ids to form the germ-plasm of the new individual, as is indicated in Fig. 87 by a circle of spheres, of which ten are white and ten black as a sign of their difference. We may think of the figure as representing the 'equatorial plate' of a nuclear spindle with its ids arranged in a circle. Now, if two organisms of this generation, with two kinds of ids, unite in amphimixis after previous reduction of the ids, we have figure _B_, in which the paternal ids (_pJ_) are seen to the left of the line and the maternal ids (_mJ_) to the right, while each semicircle is in its turn made up of two kinds of ids, those of the grandparents (_p_^2_J_ and _m_^2_J_, _p_^2_J_^1 and _m_^2_J_^1). The figures _C_ and _D_ show the two following generations, in which the number of identical ids is each time reduced to half, because eight strange ids are again mingled with them; in _C_ only two ids are still identical, and in _D_ all the ids are individually different, because they have come from different ancestors of the same species. Of course this would only be the case if inbreeding were excluded, because through it the ids of the same forefathers from two or more sides would meet; but prolonged inbreeding is a rare exception in free nature.

I shall now call the hereditary substance of a cell its 'idioplasm,' after Nägeli's example, although he sought it in the cell-substance, not in the nucleus, and had a different theoretical conception of its mode of action. It was he, however, who conceived and established the idea of the idioplasm as the bearer of the primary constituents, an _Anlagensubstanz_, determining the whole structure of the organism in contrast to the general nutritive protoplasm. Every cell contains idioplasm, since every cell-nucleus contains chromatin, but I call the idioplasm of the germ-cells _germ-plasm_, or the primary-constituent-substance of the whole organism, and the complexes of primary constituents necessary to the production of a complete individual--whose presence we have just shown to be theoretically necessary--I call _ids_. In many cases these 'ids' might be synonymous with chromosomes, at least in all the cases in which the chromosomes are simple, that is, are not composed of several similarly formed structures. Thus in the salt-water Crustacean, _Artemia salina_, which possesses 168 minute granular chromosomes, each of these chromosomes must be regarded as an id, for each can in certain circumstances be thrown out from the ovum by the reducing division, or it can be brought into the most various combinations with other chromosomes by fertilization. Each of them must therefore consist of perfect germ-plasm in the sense that all the parts of an individual are virtually contained in it; _each is a biological unity, an id_. But when we see in many animals larger band-shaped or rod-shaped 'chromosomes,' and when these are composed of a series of granules, as they are, for instance, in the often mentioned _Ascaris megalocephala_, each of these granules is to be regarded as an id. In point of fact, we find, instead of the two or four large rod-shaped chromosomes of _Ascaris megalocephala_, a larger number of smaller spherical chromosomes in other species of _Ascaris_.

Compound chromosomes consisting of several ids, such as all rod or band-like elements of the nuclear substance probably are, I designate 'idants.' That they are composed of several individual ids is not always clearly apparent because of the smallness of the object, and even in larger ones this may only be seen in certain stages. Thus we have in Fig. 88, _A_ and _B_, two 'mother-sperm-cells' of the salamander; _A_ at an earlier stage, in which the individual ids are not visible; _B_ at a later stage, in which the band has split, and the rosary-like structure has become at once apparent. It is not possible, then, to see at once whether each chromosome corresponds to one or to several ids. A more exact investigation of the processes of reducing division has shown that there are chromosomes of simple spherical form, that is, composed of several ids whose 'plurivalence' cannot be directly recognized, but can only be inferred from their further development; there are bivalent chromosomes of double value and quadrivalent chromosomes of fourfold value, which we have to think of as made up of two or four ids. It would lead us too far to go into this more precisely, nor does it fall within the scope and intention of these lectures to inquire into these intimate and still disputed details.

The germ-plasm of every species of plant or animal is thus composed of a larger or smaller number of ids or primary constituents of an individual, and it is through the co-operation of these that the individual which develops from the ovum is determined.

We have further to inquire what conception we can form of the constitution of an id and of its mode of operation. I have already spoken of 'primary constituents' (_Anlagen_) of which the germ-plasm consists, but what right have we to think of the parts of an animal as already contained in the germ in any form whatever? Is it not equally possible that the germ consists of parts, none of which bear any definite relation in advance to the parts of the finished animal? Might not the germ-cell, along with its nucleus, undergo transformations and regular changes which would successively give rise to new conditions, namely, the different stages of development, until finally the complete animal was attained?

We stand here before an old problem, before the two opposed interpretations--the theory of 'Evolution' and the theory of 'Epigenesis,' which were first ranged against each other long ago, and which are a cause of strife even now, although in somewhat different guise.

The theory of 'Evolution' is especially associated with the name of Bonnet, who elaborated it in detail in the eighteenth century. It maintains that the development of the ovum to the perfect animal is not really a new creation, but only an unfolding of invisible small parts, which were already present in the ovum. It assumes that the parts of the perfect organism are already preformed in the ovum, and on this account it is called the 'Preformation Theory.' Bonnet often speaks of the preformation of the perfect animal in the germ as a 'miniature model,' although his conception of 'evolution' was not really so crude as has been often alleged. He expressly emphasized that this miniature model was not exactly like the perfect animal, but consisted of 'elementary parts' only, which he thought of as a net whose meshes were filled up during development and by means of nutrition with an infinite number of other parts. But after all, his conceptions, and those of his time generally, were very far removed from the biological thinking of our own day, as may perhaps be most readily understood when I mention that he regarded death and decay as an 'involution,' as a folding back, so to speak, by means of which all the parts gained though nutrition were removed again, so that the net of the miniature model shrank together to the invisible minuteness that it had in the ovum. So it remained, he fancied, till it was reawakened at the resurrection, using the term in the religious sense! He afterwards dropped this fancy, because the objection was made to it that human beings who had lost a leg or an arm in this life would necessarily be maimed at the resurrection!

In Bonnet's time the facts of development were quite unknown, and not even the stages of the development of the chick from the egg had been observed. When this was afterwards done the prevalent theory of 'evolution' necessarily collapsed, for men saw with their own eyes that a miniature model of the chick did not gradually grow into visibility and ultimately into the young chick, but that first of all parts showed themselves in the egg which bore no resemblance at all to the chick, that these first rudiments were then altered, and that through continual new formations and transformations the chick finally appeared. Upon this K. von Wolff based his theory of 'Epigenesis,' or development through new formations and transformations. He maintained that the doctrine of 'Evolutio' was false; that there is no miniature model invisibly contained within the egg; but that from the simple egg-substance there arises, through the agency of the formative powers inherent in it, a long series of stages of development, of which each succeeding one is more complex than the one before, until ultimately the perfect animal is reached.

This certainly marked considerable progress, for it meant the beginning of a science of embryology, that is, the science of the form-development of the animal or plant from the ovum. The result was not so important in its theoretical aspect, for though the knowledge had been gained that the young animal goes through a long series of different stages, it had not been discovered how nature works this wonder and causes an animal of complex structure to arise from the apparently simple substance of the ovum. A solution of the difficulty was found by attributing to the ovum a formative power, afterwards called by Blumenbach the _nisus formativus_, which possessed the capacity of developing a complex animal from the simple 'slime,' or, as we should say, the simple protoplasm.

If we contrast the strictly theoretical part of the two theories, we find that Bonnet regarded the ovum as something only apparently simple, but in reality almost as complex as the animal which developed from it, and that he thought of the latter, not as being formed anew, but as being unfolded or evolved. That is to say, he thought that rudiments present from the outset in the ovum gradually revealed themselves and became visible. Wolff, on the other hand, regarded the ovum as being what it seemed, something quite simple, out of which only the _nisus formativus_ could, by a series of transformations and new formations, build up a new organism of the relevant species.

Wolff's Epigenesis routed Bonnet's theory so completely from the field that, until quite recently, epigenesis was regarded as the only scientifically justifiable theory, and a return to the 'evolutionist' position would have been looked upon as a retrograde step, as a reversion to a period of fancy which had been happily passed. I myself have been repeatedly told, with regard to my own 'evolutionistic' theory, that the correctness of epigenesis was indisputably established, that is, was a fact, verifiable at any time by actual observation!

But what are the facts? Surely only that there is a succession of numerous developmental stages, which we know very precisely in the case of a great many animals, and that the miniature model which Bonnet assumed to be in the egg does not exist. Both these facts are now no longer called in question. But that does not furnish us with a theory of development, for theory is not the observation of phenomena or of a series of phenomena, _it is the interpretation of them_. Epigenesis, as formulated first by Aristotle and again by Harvey, Wolff, and Blumenbach, certainly offered an interpretation of development, not, however, by referring only to what was observable, but by going far beyond it; on the one hand taking the _appearance_ of a homogeneous germ-substance for reality, and, on the other, assuming a special power, which caused a heterogeneous organism to arise from a homogeneous germ.

We cannot now accept either of these assumptions, for we know that the germ-substance is not homogeneous, and indeed is not merely a substance but a living cell of complex structure; and we no longer believe in a special vital force, and therefore not in a special 'power of development,' which could only be a modification of the former. We are thus as little able to accept the old epigenesis as the old evolution, and we must establish a theory of Development and Heredity on a new basis.

What this basis must be is in a general way beyond doubt. Since it is the endeavour of the whole of modern biology to interpret life more and more through the interactions of the physical and chemical forces bound up with matter, development, too, comes within this aim, for development is an expression of life. We seek to understand the mechanism of life, and, as a part of that, the mechanism of development and of heredity which is closely associated with it.

If we wished to attack the problem of heredity at its roots we should first of all have to try to understand the process of life itself as a series of physico-chemical sequences. Perhaps this will be achieved up to a certain point in the future, but if we were to wait for this we should in the meantime have to abandon all attempts at a theoretical interpretation of the phenomena of development and heredity, and might indeed have to postpone them to the Greek Kalends. That would be as though, in the practice and theory of medicine, all investigation into and speculation regarding disease had to wait until the normal, healthy processes of life were thoroughly understood. In that case we should now know nothing of bacteria diseases and the hundred other acquisitions of pathological science: physiology too would have remained far behind its present level if it had lacked the fruitful influence of experience in cases of disease, and the ideas and theories, true and false, which have been based thereon. In the same way we require a theory of development and heredity if we are to penetrate deeper into these phenomena, and must have it in spite of the fact that we are still very far from having a complete causal knowledge of the processes of life. For the raw material of observation, which is to some extent fortuitous, will never bring us any further on; observation must be guided by an idea, and thus directed towards a particular goal.

It is, however, quite possible to leave aside for the present all attempts at an explanation of life, and simply to take the elements of life for granted, and on this basis to build up a theory of heredity. We have already taken a step in that direction by establishing that the whole substance of the fertilized ovum does not take part in heredity in the same degree, but that only a small part, the chromatin of the nucleus, is to be looked upon as the bearer of the hereditary qualities, and by deducing, further, that this chromatin is made up of a varying number of small but still visible units, the ids, each of which virtually represents the whole organism, or, as I have already expressed it, each of which contains within itself, as primary constituents, all the parts of a perfect animal.

It was these 'primary constituents' which led us to the digression in regard to Bonnet's theory of 'Evolutio' and Wolff's 'Epigenesis.'

Let us now inquire what must be the constitution of such a chromatin globule, an id, so that, shut up within the nucleus of a living reproductive cell, it can direct the development of a new organism which resembles its parent. Two fundamental assumptions present themselves, and these can be related to every conception of a 'germ-plasm,' even independently of the assumption of ids. Either we may think of the id as made up of similar or of different kinds of parts, none of which has any constant relation to the parts of the perfect animal, or we think of it as composed of a mass _of different kinds of parts, each of which bears a relation to a particular part of the perfect animal_, and so to some extent represents its 'primary constituents' (_Anlagen_), although there may be no resemblance between these 'primary constituents' and the finished parts. The assumption of a germ-plasm composed of similar parts, which has been made, for instance, by Herbert Spencer, may be called the modern form of epigenesis, while the other assumption is the modern form of the 'evolution' theory. As the former theory can no longer call to its aid a 'formative power' as a _Deus ex machina_, it can only explain development as induced by the influence of external conditions--temperature, air, water, gravity, position of parts--upon the chemical components of the germ-plasm, which are everywhere uniformly mingled; and it makes no difference whether this uniform germ-plasm is thought of as composed of many different kinds of parts, as long as those parts are mingled uniformly to make the germ-plasm and bear no relation to definite parts of the developing animal. Oscar Hertwig has recently outlined such a theory. Although I cannot expound it here I must say at least so much with regard to it, and to all other theories of development founded on a similar basis, that they could not be accepted even if they were able to offer a workable explanation of the development of the individual, and for this reason, that ontogeny is not an isolated phenomenon which can be interpreted without reference to the whole evolution of the living world, for it is most intimately associated with this, being indeed a piece of it, having, as we shall see, arisen from it, and, furthermore, preparing for its continued progress. _Ontogeny must be explained in harmony with phylogeny and on the same principles._ The assumption of a germ-plasm without primary constituents, or of a completely homogeneous germ-plasm, as Herbert Spencer maintained, is irreconcilable with this, for, as will be seen, it contradicts certain facts of inheritance and variation. Therefore all theories founded on this assumption must be rejected.

There is another and, I believe, weighty consideration which forbids us to assume a germ-substance without primary constituents. I shall return to this later, but in the meantime I wish to build up more completely my own 'germ-plasm' theory.

I assume that the germ-plasm consists of a large number of different living parts, each of which stands in a definite relation to particular cells or kinds of cells in the organism to be developed, that is, they are 'primary constituents' in the sense that their co-operation in the production of a particular part of the organism is indispensable, the part being _determined_ both as to its existence and its nature by the predestined particles of the germ-plasm. I therefore call these last _Determinants_ (_Bestimmungsstücke_), and the parts of the complete organism which they determine _Determinates_, or hereditary parts.

It is easy to show on what basis this assumption rests; the phenomena of inheritance taken in conjunction with those of variation seem to me to compel us to it. We know that all the parts of an organism are variable, and that in one individual the same part may be larger, in another smaller. Not all variations are transmissible, but many of them, and some very minute ones, are. Thus, for instance, in many human families there occurs a small pit, hardly as large as the head of a pin, in the skin of the ear, whose transmission I have observed from the grandmother to the son and to several grandchildren. In such a case there must be a minute something in the germ-plasm, not present in that of other human beings, which causes the origin, in the course of development, of this little abnormality in the skin.

There are human families in which individuals occur repeatedly, and through several generations, who have a white lock of hair, in a particular spot, on an otherwise dark-haired head. This cannot be referred to external influences, it must depend on a difference in the germ, on one, too, which does not affect the whole body, not even all the hairs of the body, but only those of a particular spot on the surface of the head. It is a matter of indifference whether the white colouring of the hair-tuft is produced by an abnormal constitution of the matrix of the hair, or by other histological elements of the skin, as of the blood-vessels or nerves. It can only depend ultimately on a divergently constituted part of the germ-plasm, which can only affect this one spot on the head, and alter it, if it is itself different from what is usual. On this account I call _it_ the _determinant_ of the relevant skin-spot and hair-group. In Man such minute local variations are usually lost after a number of generations, but in animals there are innumerable phenomena which prove to us that single minute deviations can become permanent. Thus there lives in Central Europe a brown 'blue butterfly,' _Lycæna agestis_, which has a little black spot in the middle of its wing. The same species also occurs in Scotland, but there, instead of the black spot, it has a milk-white one, and so-called 'eye-spots' on the under surface of the wing have also lost their black centres. The species has thus varied transmissibly, but only in regard to these particular spots on the wing. A slight variation must therefore have taken place in the germ-plasm which only affects these few parts of the body, or, to express it otherwise, the germ-plasms of the ancestral species and of the variety can only be distinguished by a difference which determines exclusively the scale colour of these spots. The two germ-plasms differ, I should say, only as regards the _determinants_ of these wing-scales.

We know from the artificial selection to which Man has subjected and still subjects his domesticated animals and useful plants, that any spots and parts of the body which he chooses can be hereditarily altered, if the desired variations which present themselves are always selected for breeding, and that this does not necessarily cause variation in other parts of the body. When, for instance, in the case cited by Darwin, the comb of a Spanish cock which had previously hung downwards was made to stand upright because a prize had been offered for this character, or when a certain breed of hens was 'furnished with beards,' the results were permanent variations affecting only the parts on which the fancier's attention had been fixed. In the same way, when the tail feathers of the Japanese cock are lengthened to three feet the rest of the plumage does not alter, still less any other part of the body. Of course there are numerous 'correlated' variations, and in very many cases the breeder causes a second or third character, on which he had not fixed his attention, to vary in addition to the one he was aiming at. But such concomitant variations are not necessary or inevitable in all cases; and indeed we need not refer them all to a true correlation of the parts, but may suppose that they depend not infrequently on the faultiness of our power of observation, which is not sufficiently keen to control several parts of the body at one time, and to notice minimal variations in parts on which we have not specially fixed our attention.

So much, at least, is certain, that in all these cases of the artificial alteration of individual characters the germ-plasm is in some way changed, but always in such a way that it differs from that of the ancestral form through such variations alone, and the effect of these is that only the altered parts are influenced thereby, and not the whole organism. This again is but another way of saying that only the _determinants_ of these parts have altered.