regeneration-primordium consists of cells which only contain a definite
complex of determinants in the form of latent regeneration-idioplasm,
as, for instance, certain cells of the tail of Triton contain the
determinants of the tail, certain cells of its leg the determinants of
the leg, and so on. In many cases we can speak even more precisely,
and determine from which cells the nerve-centres, from which the
muscles, and from which the missing section of the food-canal will be
formed, as was recently shown by Franz von Wagner in regard to the worm
_Lumbriculus_, whose regenerative capacity is so extraordinarily high.
We must then attribute to each of the relevant cells an equipment of
regeneration-idioplasm, which includes only the relevant complex of
determinants.
I need not here go further into detail, but I should still like to
show that, in reality, as I assumed in regard to the regenerative
capacity of a part, the root of the regeneration-idioplasm lies
in the germ-plasm, that it is present there as an independent
determinant-group, and, like every other bodily rudiment (_Anlage_),
must be handed on from generation to generation. This assumption is
necessary, as has been already indicated, on the ground that the
faculty of regeneration is hereditary, and hereditarily variable, on
the same ground, therefore, as that on which the whole determinant
theory is based. The regeneration-determinants must be contained _as
such_ in the germ-plasm, otherwise a twofold phyletic development could
not have occurred, as it actually has, in many parts. The tail of the
lizard is adapted for autotomy; it breaks off when it is held by the
tip, and this depends on a special adaptation of the vertebræ, which
are very brittle in a definite plane from the seventh onwards. This is
thus a very effective adaptation to persecution by enemies. The tail
which has been seized remains with the pursuer, but the lizard itself
escapes, and the tail grows again. But this regeneration does not take
place in the same way as in the embryo; no new vertebræ are formed,
but only a 'cartilaginous-tube,' a new structure, a substitute for the
vertebral column; the spinal cord with its nerves is not regenerated
either, and the arrangement of the scales is somewhat different.
This last point, in particular, indicates that the determinants of
the regeneration-rudiment may pursue an independent phylogenetic path
of their own, for this scale arrangement of the regenerated tail
is an atavistic one, that is, it corresponds to a more primitive
mode of scale arrangement in these Saurians. We know quite a number
of cases similar to this. It not infrequently happens that cut-off
parts regenerate, but that they do so not in the modern form, but in
one that is in all probability phyletically older. Thus the legs of
various Orthoptera, as of the cockroaches and grasshoppers, regenerate
readily, but with a tarsus composed of four joints instead of five[3],
and the long-fingered claws of a shrimp (_Atyoida potimirim_) is
replaced by the older short-fingered type of claw, while in the
Axolotl an atavistic five-fingered hand grows instead of the amputated
four-fingered one.
[3] New investigations, specially directed to this point, by
R. Godelmann, have shown that 'in the great majority of cases'
the regenerated legs of a Phasmid (_Bacillus rossii_) exhibit a
four-jointed tarsus; but the regeneration of five joints also occurs,
though only after autotomy, and only in seven out of fifty cases
(_Archiv für Entwicklungsmechanik_, Bd. xii, Heft 2, July 1901).
The regeneration-rudiment in this species seems to be in process of
advancing slowly to the five-jointed type.
This last case shows that it is not merely a lesser power of growth
that accounts for the difference between the regenerated part and
the original, for here more is regenerated than was previously
present. There remains nothing for it but the assumption that the
regeneration-determinants have remained at a lower phyletic level,
while the determinants which direct embryogenesis have varied, and
either developed further or retrogressed. It is easy to understand that
the regeneration-rudiment must vary phyletically much more slowly
than the parts which evolved in the ordinary way and much more slowly
than the determinants of these parts, for natural selection means a
selection of the fittest, and the speed with which the establishment
of a variation is attained depends, _ceteris paribus_, on the number
of individuals that are exposed to selection with respect to the
varying part. If in a species of a million living at the same time
nine-tenths perish by accident, there will remain only 100,000 from
which to select the 1,000 which we will assume constitute the normal
number of the species. The more of these 100,000 which possess the
useful variation the higher will be the percentage of the normally
surviving 1,000 possessing it, and the more rapidly will the useful
variation increase. But when it is a question of the variation of
the regeneration-primordium, the selection will take place not among
all the 100,000 individuals which chance has spared, but only among
those of them which have lost a limb by accident, and thus are in
a position to regenerate it more or less completely. If we assume
that this takes place in 10 per cent. of cases, then selection for
the improvement of the regeneration-apparatus will only take place
among 1,000 individuals, and thus the process of modification of the
regeneration-primordium must go on very much more slowly than that of
the limb itself.
I do not see how the opponents of the germ-plasm theory can explain
these facts at all, for the appeal to external influences is here
entirely futile, and that to internal liberating stimuli does not
suffice, since these must be different after a part has been cut
off from what they were when the limb developed normally, and also
different from those which prevailed at the normal origin of the
limb in ancestral forms. The four-jointed tarsus of the ancestors
of our cockroaches did not arise as a result of amputation. We
cannot therefore avoid referring the processes of regeneration to
particular 'regeneration-determinants,' which are contained in the
germ-plasm and are handed on in ontogeny with the other determinants
from cell-division to cell-division, till ultimately they reach the
cells which are to respond, or may have to respond, to the stimulus
of injury by some expression of their regenerative capacity. As these
determinants, as has been shown, can often only be very slightly
subject to the influence of selection processes, they will, in many
respects, lag behind in the phyletic development, and will tend to
belong to an ancestral type of the relevant part. They will often
remain for a long time at this ancestral level, and they will always
adapt themselves to new requirements more slowly than the parts which
arise in the normal way, and the determinants representing these in
the germ. But the regeneration-determinants _are_ variable, and,
indeed, are so hereditarily, and independently of the structure of the
normal parts. They thus follow their own path of phyletic development,
and this one fact is enough to secure a preference for the germ-plasm
theory above others that have hitherto been suggested. None of these
has even attempted an explanation of this fact; the tendency has rather
been to call it in question. This, however, can be done at most only in
regard to the explanation of the regenerations as atavistic, certainly
not in regard to the progressive variations of the regenerated part,
such as have been established by Leydig and Fraisse in regard to the
lizard's tail. It may be doubted whether the most primitive insects had
only four tarsal joints, but there is no disputing the kainogenetic
deviation of the lizard's-tail.
I have interpreted the regenerative capacity as secondary and acquired,
not as a primary power of all living substance, and I should like to
substantiate this in another way.
Let us go back to the simplest organism conceivable, which must have
represented the beginning of life on our earth, and we see that this
need not have possessed any special power of regeneration, because, for
an organism without differentiation of parts, growth is equivalent to
regeneration. But growth is the direct outcome of one of the primary
characters of the living substance, the capacity of assimilation.
This cannot be an adaptive phenomenon, nor can it have arisen through
selection, because selection presupposes reproduction, and reproduction
is only a periodic form of growth; but growth follows directly from
assimilation. The fundamental characters of the living substance, above
all the dissimilation and assimilation which condition metabolism, must
have been in existence from the first when living substance arose,
and must depend on its unique chemico-physical composition. But the
faculty of regeneration could only be acquired when organisms became
qualitatively differentiated, so that each part was no longer like
every other part or like the whole. As soon as this stage was reached
the faculty of regeneration would necessarily be developed, if further
multiplication was to take place. For when each fragment could no
longer become a whole by simply growing, some arrangement had to be
made by which each fragment should receive, in the form of primary
constituents, what it lacked to make up the whole. We do not know the
first beginning of this adaptation, but, in its further development,
it appears in the form of 'nuclear substance,' enclosed in the nucleus
of the cell, and, as is well known, it is now to be found in all
unicellular organisms. That the nucleus there precedes regeneration
in the sense that without a piece of it the cell-soma is not able to
complete itself alone, we have already seen, and the explanation of
this fact has always seemed to me to be that invisibly minute vital
units relating to the regeneration of the injured part leave the
nucleus and evoke the development of the missing parts by laws and
forces still unknown to us. Loeb has recently claimed that the nucleus
is the cell's organ of oxidation; but if that be true it would still
not exclude the possibility that the nucleus is also and primarily
a storehouse of the material bearers of the primary constituents
of a species. It must be regarded as such when we call to mind the
phenomena of amphimixis in its twofold aspects as conjugation and as
fertilization, and its obvious outcome among higher organisms where it
implies the mingling of the parental qualities.
Thus the 'nuclear substance' of unicellular organisms is for us the
first demonstrable organ of regeneration, and first of all for normal
regeneration, which takes place at every reproduction, for instance,
of an Infusorian. For we have already seen that, in the transverse
division of a trumpet animalcule (_Stentor_), the anterior part must
develop the posterior half anew, while the posterior half must develop
the much more complex anterior half, with mouth region and spiral
bands of cilia. But as soon as the arrangement for normal reproduction
was elaborated, as soon as the nucleus was present, as a depôt of
'primary constituents,' this implied the possibility of regeneration
in exceptional cases, that is, after injury. The mechanism was already
there, and it came into operation as soon as a part of the animal was
missing.
It is in the first nucleus, therefore, that we have to look for
the source of all regenerative capacity, both in unicellular and
multicellular organisms. But with the origin of the latter a limitation
took place, either quite at the beginning or a little later, for each
nucleus of the cell-colony no longer contained the whole complex of
'primary constituents' or determinants of the species, but, in many
cases, only the reproductive cell possessed them. As soon as this began
to develop into a whole by cell-division the determinant-complex was
segregated. Thus the first cell-colonies with two kinds of cells arose,
as we have seen in the case of _Volvox_--the reproductive cells with a
complete equipment for regeneration in their nucleus, and the somatic
cells with a limited equipment for regeneration in their nuclei. The
somatic cell could no longer give rise anew to the whole organism, but
could only reproduce itself or its like.
But as many of the lower Metazoa and Metaphyta possess _the power of
budding_, that is, are able not only to produce a new individual
from definite cells--the reproductive cells--with or without sexual
differentiation, but from other cell-groups also, these must contain
the whole complex of determinants appertaining to the reconstruction
of the organism, and we have to ask how this is reconcilable with the
differentiation of a multicellular organism, whose different kinds of
cells depend, according to our interpretation, on the fact that they
are controlled by different determinants.
Obviously, there is only one way out of this difficulty, and it is the
one we have already indicated, that although the diffuse regenerative
capacity which we have just alluded to occurs in species which exhibit
gemmation, this does not exclude the control of a cell by a specific
determinant; other determinants may be contained in the cell, in a
state, however, in which they do not affect it, that is, in an inactive
or latent state.
Thus we arrive in this way also at our earlier assumption that an
inactive accessory-idioplasm is given to all, or at least to many
cell-generations. Only among plants must this necessarily be complete
germ-plasm, and among the lower plant-forms, as in _Caulerpa_ among
the Algæ, in _Marchantia_ among Liverworts, it must be assumed to
be present in nearly all the cells, according to the experiments
in regeneration made by Reinke and Vöchting. But in multicellular
animals which develop from two different germinal layers equipped
with a different complex of determinants budding arises from a
combination of at least two different kinds of cells, and we must
only ascribe to each of these its own peculiar determinant-complex as
regeneration-idioplasm. Higher plants show us that well-marked power
of budding is not necessarily associated with a high regenerative
capacity, the histologically specialized cells among them will contain
no inactive germ-plasm, because they do not need it. But in animals the
power of budding is probably always combined with high regenerative
capacity, as is shown by the Polyps and Medusoids above all, and in a
different way by the Ctenophores, which exhibit no budding and at the
same time a very slight regenerative capacity, although they possess
an organization scarcely higher than that of the Hydromedusæ. In the
Ctenophores each of the first segmentation-cells, when artificially
separated, yields only a half-embryo, and we may conclude from this
that it contains no complete germ-plasm in an inactive state, or at
least very little, and certainly not a sufficient quantity to make it
readily regenerative.
Undoubtedly, however, the regenerative capacity occurs apart from the
capacity for budding, yet this in no way contradicts the theory. As
we have seen, a high regenerative capacity is to be found among many
animals which occur only as 'persons' and not as colonies or stocks,
but only in those which are readily liable to injury, and only in
the manner conditioned by their injury. In the higher Metazoa the
regenerative power becomes more and more limited, and in the Mammals it
sinks to a mere closing up of wounds.
If we take a survey of the assumptions we have been compelled to
make from the standpoint of the theory to explain the development of
germ-cells, budding, and regeneration, it would seem as if it were
contradictory to assume that, on the one hand, complete germ-plasm
should be given to certain cell-series as inactive accessory idioplasm,
and, on the other, that very numerous cells, at least in the lower
Metazoa, should have received the idioplasm of budding, and still
more numerous cells that of regeneration. But it is obvious that
among the lower Metazoa the idioplasm of budding and the idioplasm of
regeneration are equivalent; the same idioplasm, which, when liberated
by stimuli unknown to us, co-operates from two or three germinal layers
in the formation of a bud, effects, in response to the known stimulus
of injury, the regeneration of the mutilated part. But germ-cells
can never arise in the Metazoa from the partial budding-idioplasm or
regeneration-idioplasm, because this is not complete germ-plasm, and
because it can only give rise to budding or regeneration through the
co-operation of two or more kinds of cells, while germ-cells always
originate from _one_ cell and never arise from the fusion of cells.
Germ-cells can thus only arise from the cells of the germ-track, and
in no other way, no matter whether the germ-track lie in the ectoderm,
as in the Hydromedusæ, or in the endoderm, as in true jellyfishes
(Acalephæ) and the Ctenophores, or in the mesoderm, as in many higher
groups of animals. It is only apparently that these cells belong to
one particular layer, for in reality they are unique in kind, and they
are simply assisted in their development by one or other cell-layer,
from which they not infrequently emancipate themselves, as happens
so notably in the Hydromedusæ. As we have already said, it is only
among plants that we must think of budding as arising from cells which
contain complete germ-plasm, for here there are no 'germinal layers'
corresponding to those of animal development, and the cells of 'the
growing point' must be equipped with the complete germ-plasm. The
plant, like the Hydroid stock and the Siphonophore colony, is saved
from death, in spite of the frequent loss of its members, mainly by
the fact that it is capable of producing, at almost any part above the
ground, buds which develop into new shoots, with leaves and the like.
This makes a power of regeneration on the part of the individual leaves
and flower-parts superfluous, but at the same time it implies that an
enormous number of cells must be distributed over the whole surface
of the plant, each of which can in certain circumstances become the
starting-point of a bud. That is to say, each must contain, in a latent
state, the complete germ-plasm which is necessary for the production of
an entire plant.
We must therefore assume that, in the higher colony-forming plants,
germ-plasm is contained in a great many cells, perhaps in all which
are not histologically differentiated, and sometimes even in those
which are so, as, for instance, in the leaves of Begonias. I suppose,
therefore, that in the higher plants the process of development implies
a segregation of the determinant-complexes of the germ-plasm, but that
this takes place at a late stage, and that in a much higher degree than
among animals the individual or the 'person' carries with it germ-plasm
in a latent state. To this must be attributed the fact that the plant
is not only able to make good its losses in twigs and branches by
sending out new shoots, but that cuttings, that is, detached shoots,
are also able to take root, and in general to give rise to what is
necessary to complete themselves according to the position of the part
in question. In the ontogeny of animals, too, we must assume that it
requires a liberating stimulus to rouse the determinants to activity,
that this stimulus is to be sought for in the influence exercised by
the constitution of the cell on the idioplasm contained within it,
and that this constitution in its turn is subject to influences from
external conditions, including the cell-soma itself. We may therefore
suppose that, among plants also, the germ-plasm latent in numerous
cells only becomes active in whole or in part according to the
influences exerted on it by the state of the cell at the moment; but
this varies with external circumstances, according to whether the cell
is exposed to light or lies under ground, according as it is influenced
by gravity, by moisture, chemical stimuli, and so on.
It might be objected to this that it would be simpler not to assume
a segregation of the germ-plasm into determinant-complexes at all in
order to explain the process of development, but rather to credit each
cell with a complete equipment of germ-plasm from the beginning to the
end of the ontogeny, and to attribute the differences in the cells,
which condition the structure of the plant and its differentiation,
solely to the different influences, external and internal, to which
the cell is exposed, and which rouse some determinants to activity at
one part and others at another. Perhaps the botanists would be more
readily reconciled to this idea, but it seems to me that there are two
points which tell against the possibility of its being correct. In the
first place, it is far from being established that every cell in the
higher plants is capable of giving rise, under favourable conditions,
to a whole new plant; every tree and every higher plant has a multitude
of cells in its leaves, its flowers, and so on, which cannot do this,
which are in fact differentiated in one particular direction, that is,
they contain only one kind of determinants, like the histologically
differentiated cells of the tissues of the human body. Secondly,
there are other organisms besides plants, and a theory of development
cannot be based on the phenomena to be observed among plants alone,
any more than a theory of heredity can. There are obvious differences
in the processes of life among plants as contrasted with those among
animals, but it is improbable that there is any thoroughly fundamental
difference. It is, however, indubitable that the cells forming the
tissues of higher animals, the nerve, muscle, and glandular cells,
are really differentiated in one direction, and are quite incapable,
under any circumstances whatever, of growing into an entire organism,
and even from this alone we might conclude that they contain only one
primordium or determinant. Are we then to assume that the vascular
cells, epidermis-cells, wood-cells, and so on, of the higher plants,
which are also differentiated in one direction, do nevertheless contain
the complete germ-plasm? I do not see any ground for such an assumption.
To conclude what can be said on the subject of regeneration we must
return to the question of an ultimate explanation of this marvellous
phenomenon. I have declined to attempt any explanation at all, because
I do not consider it possible to give a sufficient one as yet, but I
should like at least to give an indication as to the direction in which
we must look for it.