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.’