of development so as to penetrate singly into the cells they are
to control, the id must not only have the power of dividing into
daughter-ids of identical composition, it must also possess the power
of dividing under certain influences into dissimilar halves, so that
the two daughter-ids contain different complexes of determinants. The
first mode of division of the id, and with it of the nucleus and of the
cell, I call _erbgleich_, or integral, the second _erbungleich_, or
differential. The first form of multiplication is the usual one, which
we observe everywhere when unicellular organisms divide themselves into
two equal daughter-units, or when the cells of multicellular bodies
produce their like by division into two. The second is not directly
observable, because a dissimilarity of the daughter-cells, as long as
it lies only in the idioplasm, cannot be actually seen; it can only
be inferred from the different rôle which the two daughter-cells play
in the building up of the individual. When, for instance, one of two
sister-cells of the embryo gives rise to the cells of the alimentary
canal and the other to those of the skin and the nervous system,
I infer that the mother-cell divided its nuclear substance in a
differential way between the two daughter-cells, so that one contained
the determinants of the endoderm, the other those of the ectoderm; or
when a red and a black spot lie side by side and under exactly the same
conditions on the wing of a butterfly, I conclude that the ancestral
cells of these two spots have divided differentially, so that one
received the 'red,' the other the 'black' determinants. Our eyes can
perceive no difference between the nuclear substance of the two cells,
but the same is true of the chromosomes of the paternal and maternal
nuclei in the fertilized ovum, although we know in this case that
they contain different tendencies. In any case we are not justified
in concluding from the apparent similarity of the chromosome-halves
in nuclear division that there cannot be differential division. The
theoretical possibility that there is such differential division cannot
be disputed; indeed, I am inclined to say that it is more easily
imagined than the division of the ids into absolutely similar halves.
Both are only conceivable on the assumption that there are forces which
control the mutual position of the determinants in the ids, that is, on
the assumption of 'affinities.' I shall not follow this further, but
that there are forces operative within the ids which are still entirely
unknown to us is proved at every nuclear division by the _spontaneous_
splitting of the chromosomes.
It has been objected to my theory that such a complex whole as the
id could not in any case multiply by division, since there is no
apparatus present which can, in the division into two daughter-units,
re-establish the architecture disturbed by the growth. But this
objection is only valid if we refuse to admit the combining forces, the
'vital affinities' within the ids, and the same is true for the smaller
vital units. An ordinary chemical molecule cannot increase by division;
if it be forcibly divided it falls into different molecules altogether;
it is only the living molecule, that is, the biophor, which possesses
this marvellous property of growth and division into two halves similar
to itself and to the ancestral molecule, and we may argue from this
that in the division of the ids forces of attraction and repulsion must
likewise be operative[19].
[19] In my book _The Germ-Plasm_ I have already assumed the existence
of 'forces of attraction' in the determinants and biophors, as in the
cells. I did not, indeed, enter into details, but I argued on the same
basis as now (_Germ-Plasm_, p. 64, English edition). My critics have
overlooked this.
I see no reason why we should not assume the existence of such
forces, when we make the assumption that the hundreds of atoms which,
according to our modern conceptions, compose the molecule of albumen
and determine its nature, are kept by affinities in this definite and
exceedingly complex arrangement. Or must we suppose that between the
atom-complex of the molecule and the next higher atom-complex of the
biophor, determinant, and id there is an absolute line of demarcation,
so that we must assume quite different forces in the latter from those
we conceive of as operative in the former? The biophor is ultimately
only a group of molecules, the determinants a group of biophors, the
id a group of determinants, and all the three inferred stages of vital
organization only become real units through the forces operating within
them and combining them into a whole. What compels the chromatin
granules of the resting nucleus to approach each other at the time of
cell-division, to unite into a long, band-like thread, and what is it
that subsequently causes this thread to break up again into a definite
number of pieces? Obviously only internal forces of which we know
nothing further than that they are operative.
We shall see later that this assumption of vital affinities must be
made not only in regard to the cells, but also in regard to entire
organisms whose parts are united by an internal bond, and whose
co-ordination is regulated by forces of which we have as yet no secure
knowledge. In the meantime we may designate these forces by the name of
'vital affinities.'
It must be admitted, however, that some objections of a fundamental
nature have been urged against the assumption of a differential nuclear
division of the hereditary substance. O. Hertwig holds that the
assumption of differential division is essentially untenable, because
it is contradictory to 'one of the first principles of reproduction,'
for 'a physiologically fundamental character of every living being is
the power of maintaining its species.'
This certainly seems so, but a closer examination shows that this
'principle,' although correct enough when taken in a very general
sense, does not really cover the facts, and is therefore incapable
of supporting the inferences drawn from it. If the proposition
expressed the whole truth there could have been no evolution from
the primitive organisms to higher ones, every living being must have
simply reproduced exact copies of itself. Whether the transformations
of species have been sudden or gradual, whether they have been brought
about by large steps or by very small ones, they could only have come
about by breaking through this so-called 'principle' of like begetting
like. In fact, we may with more justice maintain the exact converse
of the principle, and say that 'no living being is able to produce an
exact copy of itself,' and this is true not only of sexual, but of
asexual reproduction.
In ontogeny we see exactly the same thing. There are no two
daughter-cells of a mother-cell which are exactly alike, and the
differences between them, if they increase in the same direction, may
lead in later descendants to entire differences of structure. Indeed
the whole process of development depends on such an augmentation
of the differences between two daughter-cells--on differences which
proceed from within and are definitely pre-established. Here, again,
the facts do not justify us in making a dogma of the proposition that
it is a 'fundamental power' of every living being to maintain its
species by producing replicas of itself. If we look at two directly
successive cell-generations, we can hardly, it is true, in most cases,
perceive any difference between them, just as in the generations
of species; but if we compare the end of a long cell-lineage with
the beginning, then the difference is marked, and we recognize that
the difference is due to a gradual summing up of minute, invisible
deviations. In my opinion these steps of difference cannot possibly
depend merely on direct external influences; they proceed rather from
the hereditary substance the cell receives from the ovum, which,
therefore, in order to attain to such many-sided and far-reaching
differentiation, must have undergone a frequently repeated splitting
up of its qualities. That this splitting is not merely a variation
to which the whole of the hereditary substance of the daughter-cells
is uniformly subject, according to the influences dependent on their
position in relation to other cells of the embryo, will be made clear
from the case of the Ctenophora referred to in the next lecture. A
scarcely less striking example is that of those animals in which the
ova contain the primary constituents for only one sex, in which, in
other words, there are 'male' ova and 'female' ova. This is the case,
for instance, among Rotifers, and in plant-lice such as the vine-pest,
_Phylloxera_. Here the eggs from which males develop are smaller than
those which produce females. The primary constituents for both male
and female are not, as in most animals, contained in the same ovum,
to be liberated on one side or the other by influences unknown to
us, but in each ovum there is only one of the two sets of primary
constituents present, and in this case, therefore, the development of
hermaphrodites, which not infrequently occur in other animals, would
be impossible. But all these ova have been produced by one primitive
reproductive cell, and consequently, at one of the divisions implied
in the multiplication of this first cell, a separation of the male
from the female primary constituents must have taken place, that is, a
differential division of hereditary substance, for which no external
and no intercellular influences can possibly account.
If there is, then, a differential division of the ids and with them
of the whole idioplasm, the germ-plasm of the fertilized ovum must
be broken up in the course of ontogeny into ever smaller groups of
determinants. I conceive of this as happening in the following manner.
In many animals the fertilized ovum divides at the first segmentation
into two cells, one of which gives rise predominantly to the outer,
the other to the inner germinal layer, as in molluscs, for instance.
Let us now assume that this is the case altogether, so that one of the
first two blastomeres gives rise to the whole of the ectoderm, the
other to the whole of the endoderm; we should here have a differential
division, for the developmental import (the 'prospective' of Driesch)
of the primitive ectoderm-cell is quite different from that of the
primitive endoderm-cell, the former giving origin to the skin and the
nervous system, with the sense organs, while the second gives rise
to the alimentary canal, with the liver, &c. Through this step in
segmentation, I conclude, the determinants of all the ectoderm-cells
become separated from those of the endoderm-cells; the determinant
architecture of the ids must be so constructed in such species that
it can be segregated at the first egg-cleavage into ectodermal and
endodermal groups of determinants. Such differential divisions will
always occur in embryogenesis when it is necessary to divide a cell
into two daughter-cells having dissimilar developmental import,
and consequently they will continue to occur until the determinant
architecture of the ids is completely analysed or segregated out into
its different kinds of determinants, so that each cell ultimately
contains only one kind of determinant, the one by which its own
particular character is determined. This character of course consists
not merely in its morphological structure and chemical content, but
also in its collective physiological capacity, including its power of
division and duration of life[20].
[20] Emery has lately called attention to another direct proof of the
existence of differential cell- and nucleus-division. According to
observations made by Giardina, in the water-beetle (_Dytiscus_), one
primitive ovum-cell gives rise, through four successive divisions,
to fifteen nutritive cells and one well-defined ovum-cell. But only
half of the nuclear substance takes part in these divisions, the rest
remains inactive in a condensed, cloudy condition. 'The meaning of
the whole process is obviously that the germ-plasm mass as a whole is
handed over to the ovum-cell, while the nutritive cells receive only
the nuclear constituents which belong to them' (_Biol. Centralbl._, May
15, 1903).
But embryogenesis does not proceed by differential divisions alone,
for integral divisions are often interpolated between them, always,
for instance, when in a bilateral animal an embryonic cell has to
produce by division into two a corresponding organ for the right and
left sides of the body; for instance, in the division of the primitive
genital cell into the rudiments of the right and left reproductive
organs, or in the division of the primitive mesoderm-cell into the
right and left initial mesoderm-cell, but also later on in the course
of embryogenesis, when, for instance, the right or the left primitive
reproductive cell multiplies into a large number of primitive
germ-cells, or in the multiplication of the blood-cells, or of the
epithelial cells of a particular region; in short, whenever mother and
daughter-cells have the same developmental import, that is, when they
are to become nothing more than they already are. In all such cases a
similar group of determinants, or a similar single determinant, must in
the nuclear division penetrate into each of the two daughter-cells.
It is in this way, it seems to me, that the determinants gain entrance
into the cells they are to control, by a regulated splitting up of the
ids into ever smaller groups of determinants, by a gradual analysis
or segregation of the germ-plasm into the idioplasms of the different
ontogenetic stages. When I first developed this idea I assumed that the
splitting process would in all cases set in at the same time, namely,
at the first division of the ovum. But since then, in the controversies
excited by the theory, many facts have been brought to light which
prove that the ova of the different animal groups behave differently,
and that the splitting up of the aggregate of primary constituents may
sometimes begin later--but I shall return to this later on.
If we accept the segregation hypothesis, which is similar in purport
to that advanced by Roux as the' mosaic theory,' it must strike us
as remarkable that the chromatin mass of the nucleus does not become
notably smaller in the course of ontogeny, and even ultimately sink to
invisibility. Determinants lie far below the limits of visibility, and
if there were really only a single determinant to control each cell
there would be no chromatin visible in such a case. This objection has
in point of fact been urged against me, although I expressly emphasized
in advance the assumption that the determinants are continually
multiplying throughout the whole ontogeny, so that in proportion as the
number of the _kinds_ of determinants lying within a cell diminishes
the number of resting determinants of each kind increases. When,
finally, only one kind of determinant is present there is a whole army
of determinants of that kind.
It follows from this conception of the gradual segregation of the
components of the id in the course of development that we must
attribute to the determinants two different states, at least in regard
to their effect upon the cell in which they lie: an active state,
in which they control the cell, and a passive state, in which they
exert no influence upon the cell, although they multiply. From the
egg onwards, therefore, a mass of determinants is handed on by the
cell-divisions of embryogenesis, which will only later become active.
My conception of the manner in which the determinants become active is
similar to that suggested by De Vries in regard to his 'Pangens,' very
minute vital particles which play a determining part in his 'pangen
theory,' similar to that filled by the determinants in my germ-plasm
theory. It seems to me that the determinants must ultimately break
up into the smallest vital elements of which they are composed, the
biophors, and that these migrate through the nuclear membrane into the
cell-substance. But there a struggle for food and space must take place
between the protoplasmic elements already present and the newcomers,
and this gives rise to a more or less marked modification of the
cell-structure.
It might be supposed that the structure of these biophors corresponded
in advance to certain constituent parts of the cell, that there were,
for instance, muscle biophors, which make the muscle what it is, or
that the plant-cells acquired their chlorophyll-making organs through
chlorophyll biophors. De Vries gave expression to this view in his
'pangen theory,' and I confess that at the time there seemed to me
much to be said for it, but I am now doubtful whether its general
applicability can be admitted. In the first place, it does not seem
to me theoretically necessary to assume that the particles which
migrate into the cell-bodies should themselves be chlorophyll or muscle
particles; they may quite well be only the architects of these, that
is to say, particles which by their co-operation with the elements
already present in the cell-body give rise to chlorophyll or muscle
substance. As we are as yet unacquainted with the forces which dominate
these smallest vital particles, as well as the processes which lead
to the histological differentiation of the cells, it is useless in
the meantime to make any further hypotheses in regard to them. But in
any case the biophors which transform the general character of the
embryonic cells into the specific character of a particular tissue-cell
must themselves possess a specific structure different from that of
other biophors, for they must keep up the continuity of the structures
handed on from ancestors, chlorophyll and muscle-substance and the
like, since we cannot assume that these structures, so peculiar and so
complex in their chemical and physical constitution, are formed afresh,
so to speak, by spontaneous generation in each new being, as De Vries
has very rightly emphasized. A specific biophor, for instance, of
muscle substance will produce this substance as soon as it has found
its way into the appropriate cell-body, even though it may not be a
contractile element itself.
To this must be added that the structure of the body and the
distinctive features of an organism do not depend merely on the
histological differentiation of the cells, but quite as much on
their number and arrangement, and on the size and on the frequency
of repetition of certain parts. These distinctive characters are just
as constant and as strictly transmissible, and may be as heritably
variable as those which depend on specific cell-differentiation, and
they must therefore likewise be determinable by definite elements of
the germ-plasm. Obviously enough, however, these elements are not
of the same nature as the known specific histological elementary
particles; they can be neither nerve-, muscle-, nor gland-biophors.
They must rather be vital units of such a kind that they communicate
to the cells and lineage of cells, into whose bodies they migrate from
within the nucleus, a definite vital power, that is, an organization
which regulates the size, form, number of divisions, and so on, of
these cells--in short their whole prospective significance. Always,
however, they act in co-operation with the cell-body into which they
have penetrated.
Throughout we must hold ourselves aloof from the idea that 'characters'
are transmissible. It is customary, indeed, to speak as if this
were so, and it is also necessary, because we can only recognize
the 'characters' of a body, and not the essential 'nature' on which
these characters depend; but the determinants are not seed-grains of
individual characters, but co-determinants of the nature of the parts
which they influence. There are not special determinants of the size
of a cell, others of its specific histological differentiation, and
still others of its duration of life, power of multiplication, and so
on; there are only determinants of the whole physiological nature of a
cell, on which all these and many other 'characters' depend. For this
reason alone I should object to the assumption that the determinants of
the germ are ready-made histological substances. That is as unlikely
as that their groups in the germ-plasm are 'miniature models' of the
finished parts of the body.
I conceive of the process of cell-differentiation as follows: at every
cell-stage in the ontogeny determinants attain to maturity, and break
up so that their biophors can migrate into the cell-bodies, so that the
quality of each cell is thus kept continually under control, and may
be more or less modified, or may remain the same. By the 'maturity'
of a determinant I mean its condition when by continual division it
has increased in number to such a point that its disintegration into
biophors and their migration into the cell-substance can take place.
One more point I must touch upon here, the question of the 'liberation'
or 'stimulation' of the determinants. The activity of an organ never
depends on itself alone; the contraction of a muscle is induced by
a nerve stimulus or by an electric current; the activity of the
nerve-cells of the brain requires the continual stimulus of the
blood-stream, and cannot continue to exist without it; the specific
sensory-nerves and sense-cells of the eye, ear, olfactory organ, and
so on, are all prompted to activity by adequate stimuli. The same is
true in regard to the determinants, they must be 'liberated' if they
are to distribute themselves and migrate into the cell-body; and we
have to ask how that happens, whether it is possibly due only to their
own internal condition, which again would, of course, depend on the
nutritive conditions of the cell in which they lie, or whether it is
perhaps due to some specific stimulus which is necessary in addition to
the fact of 'maturity,' just as a muscle is always ready to contract,
yet only does so when it is affected by a specific stimulus.
From the very first, therefore, I have considered whether it would
not be better to elaborate the determinant theory in such a way that
it would not be necessary to assume a disintegration of the id in
the course of ontogeny, but simply to conceive of every expression
of activity on the part of a determinant as dependent on a specific
stimulus, which in many cases can only be supplied by a definite cell,
that is, by internal influences, and in other cases may be due to
external influences.
Darwin assumed the first of these alternatives in his theory of
Pangenesis, which we have still to outline. In it he attributes to
his 'gemmules' the power of giving rise to particular cells, which,
however, they can only accomplish when they reach the cells which are
the genetic antecedents of those which the gemmules are to control.
Translated into the language of our theory this view would read
as follows: the whole complex of determinants is contained within
every cell, as it is contained in the germ-cell, but at every stage
of ontogeny, that is, in each of the developing cells, only the
determinant which is to control the immediately successive cells is
'liberated,' and that through the stimulus which the specific nature
of the cell supplies to the determinant. In that case there would
necessarily be in every species of animal as many specific stimuli for
determinants as there are determinants. This appeared to me improbable,
and I rejected the hypothesis because of the enormous number of
specific stimuli which it demands, but also on other grounds which will
be touched upon in the course of these lectures.
Although the assumption of an autonomic dissolution of the determinant
complexes of the id in the course of ontogeny seems to me imperative,
I do not by any means reject the interposition of liberating stimuli,
indeed I regard their co-operation as indispensable. Later on we shall
discuss cases in which it is definitely demonstrable that there may be
two alternative sets of homologous determinants present in a cell, but
that on any occasion only one of these becomes active, a fact which we
can only explain on the assumption that only one of these is affected
by the specific liberating stimulus. The phenomena of regeneration, of
polymorphism, of germ-cell formation, &c., compel us to the assumption
that numerous cells, even after the completion of the building up of
the body, contain two or more kinds of determinants, as in a sense
inactive 'accessory idioplasm,' each of which could control the cell
alone, though in reality it only does control it when it is affected by
the appropriate liberating stimulus. I stated this view some years ago
when I attempted to define more precisely the rôle played by 'external
influences as developmental stimuli[21]'. It is not, then, that I
underrate the importance of external influences on the organism, but
I believe that a still larger part of the determination of what shall
happen at a particular point depends on the primary constituents, and
that these are not alike at all parts of the body.
[21] _Äussere Einflüsse als Entwicklungsreize_ [External Influences as
Stimuli to Development], Jena, 1894.