was able to rear successive embryonic stages (_Gastrula_ and _Pluteus_),
which were normal in shape, but one-half the usual size. Wilson's results,
obtained by shaking apart the segmentation spheres, were even more
interesting, as they were performed upon amphioxus, a more highly-organized
animal. He reared gastrulae and older embryos with notochord and nerve-tube,
which were perfect and normal, except in size. They were one-half,
one-quarter, or one-eighth of the usual size, according as they were reared
from cells isolated from the two, four, or eight-celled stage of the
segmenting egg.
Results which Chabry and I gained by destroying, by puncture, one of the
first two segmentation spheres, assist the present argument. Although
one-half of the mass had been destroyed, Chabry obtained, in the case of an
ascidian, and I obtained, in the common frog, embryos with notochord and
nerve-plate. These developed directly and normally, although, in the case
of the frog, there was a slight defect at the ventral posterior part of the
body, where the arrested protoplasmic mass came to lie.
All these experiments show that the first two (and in some cases the first
four) results of division can assume a quite different bearing as regards
their function in the mechanical building of the embryo, according to
whether they remain bound with each other into a whole or are separated and
develop by themselves. In the former case, each forms only one-half (in
some cases only a fourth) of the whole. In the latter case, each by itself
produces the whole. The half and the whole, then, of the first
cleavage-cells are identical in real nature, and, according to the
circumstances, can develop, now in this way, now in that.
Even if Weismann were to admit the correctness of these experiments,
perhaps he would not consider that they contradicted his theory of the
germplasm and the segregation of the hereditary mass, but would make a
supplemental hypothesis, which, from the spirit of his theory, could be
none other than this: each of the first cleavage-cells, in addition to its
specific part of the hereditary mass, the part that controls its normal
course of development, possesses an accessory idioplasm, an undivided
fragment of the germplasm, left behind to be ready for unforeseen
emergencies; this part takes command when, in consequence of violence, a
separated part develops into the whole.
But such an assumption does not go far enough, if it be confined to the
first cleavage-cells. By compression of the frog's egg, I have shown that
the pole passing through the blastopore, which coincides with the chief
axis of the future embryo, may assume different relations to the first
segmentation-plane, sometimes coinciding with that, sometimes making a
right or an acute angle with it. It is clear that in each of these cases
the embryonal-cells take a different share in the formation of the regions
of the body, and that they must be fore-endowed with the capacity of
playing different parts.
The developmental history of double monsters enforces the same doctrine;
such are common among the embryos of fish, and rather less common among
chicks. From causes of which we are ignorant two, instead of one, gastrula
stages may arise at separate regions of the germinal layer of the egg.
According to the position of these two invaginations, which may be regarded
as crystallisation-points for the formation of the future embryo, the cells
of the germinal disc will be drawn into the process of development, and,
falling into groups, will build up organs. In relation to this double
gastrulation, there may arise, for instance, four instead of two primitive
ears, eyes, and nasal organs; and these arise from cell-groups, the choice
of which is determined by their relation to the position of the
gastrula-invagination.
From various other experiments, conducted so as to distort the normal
course of development, I have obtained parallel results.
Taking frogs' eggs immediately after fertilisation, I compressed them
strongly between parallel, horizontally placed glass plates. I then
inverted them, so that the vegetative pole came to lie uppermost. In spite
of their unnatural relation to gravity, they developed further, and became
abnormal, quite unsymmetrical embryos.
In another experiment, taking a triton's eggs after they had divided into
two spheres, I surrounded them with a silk thread in the plane of the first
cleavage, and tightened the thread until the embryo assumed the form of a
sand-glass. The deformity of the resulting larvae was very different, and
perhaps depended on the tightness of the constriction. Some became greatly
elongated, and had developed so that the thread surrounded the dorsal
nerve-cord. In other cases the dorsally-placed organs arose only from
one-half of the sand-glass-shaped embryo, while the other half gave rise to
the ventral part of the body. In this case the dorsal organs (nerve-tube
and notochord) were doubled over like a snare, the head and tail ends, the
mouth and the region of the anus, being bent in at the position of the
constricting thread.
The important point is that in both the experiments, in the case of the
frog and of the triton, the cell-material, separated at the first cleavage,
was turned to a use quite different to its use in the formation of a normal
embryo.
We may conclude with a very convincing proof. In the above-mentioned
abnormal development of the frog's egg it happened that one edge of the
blastopore, on account of its weight, was very much bent outwards. In
consequence of this the cleft of the blastopore lay between the normal
blastopore-lip and the everted border of the other lip. When the notochord
and the nerve-plate appeared, as a result of this abnormal condition, they
grew from a cell-material that was quite different to that which gives them
origin in normal cases.[15]
In these cases Weismann cannot apply his accessory conception, the
existence of supplementary idioplasm, only to the nuclei arising from the
first division; he must extend it to the thousands of embryonic cells that
arise by division up to the time for the appearance of the nerve-tube and
notochord. The behaviour of these cells under fortuitously changed
conditions shows them all to be endowed with the capacity of development in
different directions.
FIFTH GROUP OF FACTS.--PHENOMENA OF VEGETATIVE AFFINITY.[16]
Many considerations, taken from the region of general physiology, support
the view that all the cells of an individual, of any species, are alike,
and are to be distinguished from one another only by the special
development of one character.
Formerly, indeed, many biologists, relying upon the optical appearances
presented in microscopical investigation, have been inclined to the view
that the visible qualities of a tissue, as revealed by the microscope, were
the only, or the chief, distinctive characters. For instance, by
microscopical investigation one cannot distinguish the tendons, nerves,
bones, and cartilages of a dog from the corresponding tissues in a horse.
So far as their special use in the organism goes, one might interchange the
corresponding parts in these two mammals. A tendon from the dog, if large
enough, might be attached to the muscle of a horse, and would transmit the
pull of the muscle on the bone just as well, and would completely satisfy
the mechanical duties of the horse's tendon. The same might happen in the
case of a bone, of a cartilage, or of a nerve-fibre.
As a matter of fact, the idea that parts of the tissues of different
animals may serve to replace one another has been employed repeatedly in
science, especially in the science of medicine. But I believe that our
ideas are not yet clear upon the matter. The erroneous impression to which
I have alluded has arisen because we do not bear in mind that each tissue,
each part of an organ, each cell, possesses, in addition to its obvious
characters, very many characters that are invisible to us. Such characters
are inherent in the tissue-cells because these are parts of a definite
organism. In consequence of their specific tissue characters, which are
visible to us, we assign cells their place in histological classification;
in contrast, we may denote the other characters as constitutional, or
species, characters.
No doubt tissue cells are in the same case as genital cells. So far as
microscopical characters go, egg cells and spermatozoa are wonderfully
alike in all the mammalia; in many cases we could not distinguish between
those of different animals. But, because they bear the specific characters,
we cannot doubt but that they are as distinct as are the species, although
invisibly to us.
The products of the sexual cells show us clearly enough that out of each
kind of egg only its own species of organism can be developed. Certainly it
is not so plain that, besides their visible microscopical characters, the
tissues and organic parts are in possession of more general characters,
identical in all the differently-specialised tissues of a single organism;
but we may infer the existence of such latent characters, at least partly,
from the results obtained, in the case of plants, by grafting, in the case
of animals, by transplantation and transfusion.
In the case of plants one may graft a twig cut from one tree upon the stem
or lower part of another tree of the same kind, and so bring about a firm
and lasting union between the two. In a short time the corresponding
tissues of the parts brought into connection quietly unite. Thus from two
different individuals a single living organism may be produced
artificially.
One would expect, therefore, that a twig and stem, chosen from two closely
allied species, such as, for instance, the pear and the apple, would unite
when the suitable tissues were put together. But this does not happen.
Successful grafting depends far less on the conjunction of obviously
appropriate parts than upon characters unrecognisable by us, such as
deep-seated kinship between the parts, and the specific characters of their
cells; while in the case of individuals of the same species two pieces will
unite even if they are not brought together in appropriate conjunction, or
when they belong to different parts of the organism, as, for instance, to
the root and the leaf; yet in the absence of deep-seated kinship union will
not take place.
Generally this kinship, which has been called vegetative affinity, depends,
like sexual affinity, upon the degree of systematic relationship. It
appears that the same condition of things occurs as when, in ordinary
fertilisation, sexual cells from different varieties, or species, are
united. In both cases it happens, on the average, that union is the more to
be expected the more closely the plants concerned are akin, in a natural
system of classification.
But in grafting, as in cross-fertilisation, unexpected exceptions to this
rule occur. Relying upon these, Naegeli thought that the external
distinguishing tokens do not always indicate correctly the intrinsic
constitutional differences. Frequently union will not take place between
plants most near akin in classification, most alike in external characters;
while it will occur between plants most different in outward aspect and
belonging to different genera or even families. In other words, external
characters give no certain index to the degree of vegetative affinity or of
sexual affinity between two kinds of plants.
As an example of this, Voechting, in his treatise upon transplantation of
plant-tissues, takes the tribes of pear-trees. Grafting between these and
apple-trees takes place only with difficulty, although the apple is a close
kinsman and belongs to the same genus. On the other hand, most of them
graft easily upon the quince, although that belongs to a different genus.
In this case, also, there is no sexual affinity between the pollen and the
ova. Hybrids are not formed between the pear and the apple.
It seems probable to me, although as yet I cannot get complete proof of it,
that sexual and vegetative affinity, that is to say, the relationship
between the egg-cell and the pollen of two species, and the relation
between twig and stem, depend upon the same intrinsic qualities of that
elementary organism the cell.
Voechting distinguishes as harmonic or disharmonic the modes of union
between twig and stem, according to whether or no they reach the formation
of functional unity. Among cases of disharmony there are several
interesting gradations. Generally speaking, in the case of plants not
adapted to each other, no attempt at union occurs, and the grafted twig
speedily perishes; sometimes even the stem dies, as if it had been poisoned
by the graft. In other cases the disharmony is not shown so strongly. The
twig and the stem begin to unite, but, sooner or later, disturbances occur,
and complete destruction results. According to Voechting, in the case of
some _Cruciferae_ the disturbances are as follows: the twig begins to form
roots at its lower end, and these grow into the stem of the host. Through
them the twig uses as food the juices and salts of the stem, refusing to
unite with the stem so as to form a single individual. As Voechting says,
this formation of roots simply is an attempt on the part of the twig to
complete its own individuality. Instead of growing into corporate union
with the stem, the twig attempts to become a parasite upon it. A further
consequence often is, that the stem, too, begins to respond to the
unadaptive stranger's influence. Thus, when Voechting grafted a _Rhipsalis
paradoxa_ on an _Opuntia labouretiana_, he found that round the roots of
the graft the tissues of the host threw out a protective sheath of cork, or
turned in places to a gelatinous mass.
In some cases experimenters have overcome disharmony between two species, A
and B, by making use of a third species, C, with a vegetative affinity for
both A and B. Thus, an intermediary between the two disharmonic forms is
made, and by such an arrangement a single functional individual is produced
from pieces of three different species. Thus, upon A, as stock, a shoot of
C is grafted, while upon this shoot of C, as stock, a shoot of B in turn is
grafted.
In the matter of these different grades of disharmony, a comparison may be
made between sexual and vegetative affinities. In many cases the
spermatozoa of one species will not impregnate the eggs of another species.
In other cases, the alien spermatozoon may penetrate the egg and unite with
its nucleus, making, however, an unsatisfactory combination in various
degrees of infertility. Sometimes the fertilised egg divides only a few
times and then dies; sometimes development proceeds to the stage of the
blastula, the gastrula, or even further; but it then comes to an end,
through intrinsic causes beyond our ken, and, finally, complete destruction
follows.
Our acquaintance with what happens in transplantation of animal tissues is
smaller than in the sphere of botany.
Long ago, Trembley attempted to cause, by grafting, the union of two pieces
of hydroid polyps into a single individual. He divided, across their
middles, two specimens of _Hydra fusca_, and then, in a watch-glass,
applied the upper end of one to the lower end of the other. In one case he
was rewarded by the occurrence of complete union; for, after a few days, on
feeding the upper end with a worm, it was passed on into the lower end.
Later on buds arose, both above and below the point of union. Trembley,
however, was unable to graft on each other parts of different species,
parts of the green hydra, _Hydra viridis_, upon the common hydra.
Transplantations of single tissues or organs have been made more often, and
by several investigators. I shall mention only the older results of Ollier
and M. Bert, and those made in 1893 by A. Schmitt and Beresowsky.
Ollier exposed the bone of an animal, and, carefully removing a part of the
periosteum, planted it in the connective tissue under the skin in another
part of the body. The consequences differed according as the transplanted
tissue was imbedded in another animal of the same species, or of another
species. In the first case the piece of periosteum grew, obtaining a supply
of blood from vessels which grew out into it from the surrounding
connective tissue in which it was embedded. In a short time lamellae of bone
were formed by the layer of osteoblasts, so that a small plate of bone was
formed under the skin. This, however, proved always but a temporary
structure, for, being formed in an inappropriate spot, and, therefore,
being functionless, it was soon reabsorbed. In the second case, however, in
which the piece of periosteum was removed from the bone of a dog and
planted in a cat, rabbit, goat, camel, or fowl (or _vice versa_), formation
of bone did not occur; either the piece of periosteum was absorbed, or set
up suppuration around it, or became enclosed in a cyst.
Paul Bert's experiments were the following. He removed pieces two or three
centimetres long from the tails of white rats a few days old, skinned each
piece, and planted it in the connective tissue under the skin of the same
animal. In a few days circulation of blood was established in the pieces of
the tails, by union with vessels from the connective tissue in which they
were embedded. Muscles and nerves degenerated, but the other tissues,
bones, cartilages, and connective tissue, grew vigorously, so that, in
animals killed and examined a month after the operation, the pieces of
tail, implanted when they were two or three centimetres long, had grown
five to nine centimetres long.
The result was totally different when the transplantation was made from one
species to another. When the tip of the tail of a _Mus decumanus_ or a _Mus
rattus_ was transplanted to a squirrel, guinea-pig, rabbit, cat, dog (or
_vice versa_), either extensive suppuration took place, and the piece was
extruded, while sometimes the subject of the experiment died; or, after a
less turbulent course, the alien piece was absorbed. The continuance of
life and growth in the piece only took place when the two animals concerned
were allied very closely. Thus success followed transplantation from _Mus
rattus_ to _Mus decumanus_ (or _vice versa_), but not when it was from _Mus
sylvaticus_ to _Mus rattus_.
The recent experiments of A. Schmitt and Beresowsky lead to the same
conclusion. The former succeeded in making pieces of living bone 'take'
only when the transplantation was from one individual to another of the
same species, or to another part of the same individual. Beresowsky
transplanted pieces of frog's skin to the dog and the guinea-pig, and
pieces of dog's skin to the guinea-pig, and always found that they died, or
were thrust out as foreign bodies.
Precisely the same results follow transfusion of blood between animals of
different species. There is complete agreement among investigators. When
the blood is made to flow directly from the vessels of one animal to the
vessels of an animal of a different species, as from the dog to rabbit, or
from dog to sheep (or _vice versa_); or when it has been first freed from
fibrin and then injected, the result is always the same. 'We have always
found,' says Ponfick, summing up the results of the investigation, 'not
only that blood of another species acts in strong doses as a poison, and in
weaker or smaller doses is harmful, but that (and this seems to me my most
important result) in every case the blood-corpuscles are destroyed almost
completely, probably quite completely.' In a very few minutes, in the case
of disharmonic kinds of blood, the red corpuscles degenerate, and the
haemoglobin, becoming dissolved in the blood-plasma, soon appears in the
urine. In the case of transfusion of similar blood between individuals of
the same or of very closely related species, the haemoglobin does not appear
in the urine except after very large doses; and Ponfick infers that the red
blood-corpuscles, either all of them or most of them, remain unchanged in
the new animal.
Landois has carried out transfusion between the remotest species, between
different families of mammals, and between mammals, birds, and amphibia;
from these he drew 'the inference, important for classification of animals,
that those animals anatomically most nearly allied have their blood most
closely alike.' In fact, 'the destruction of the foreign blood happens the
more slowly the more nearly the animals are allied.' 'Thus, in doubtful
cases, experiments on transfusion might settle degrees of relationship.
Between individuals of the same species transfusion is a complete success;
when the species are closely allied, the transfused blood disappears only
very gradually, and large quantities may be transfused without harm. The
further apart the animals may be, in a system of classification, the more
violently the destruction of the foreign blood takes place, and the smaller
is the quantity that can be endured in the vessels. Thus, in the extent to
which blood transfusion may occur, I see a step towards the foundation of a
Darwinian theory applied to cells.'
As yet, transplantations and transfusions between animals of different
species have been considered with a view to their importance in surgery and
in medicine, rather than from their purely physiological side. From the
results given above, in which I believe, although there might be drawn from
literature contradictory results--in which, however, I cannot feel
confident--I am prepared to extend a conclusion to the animal kingdom that
is better supported in botany: the conclusion that the cells and tissues
possess, in addition to their definite microscopical characters, more
general, intrinsic, specific characters, and, that one may speak of the
vegetative affinities between tissues exactly as one speaks of the sexual
affinities between reproductive cells.
SUMMARY OF THE CONCLUSIONS IN THE FIRST SECTION.
Summing up what has been said in the preceding pages, we find a large
series of facts supporting our contention that cells multiply only by
doubling division. First comes the fundamental circumstance that
single-celled organisms exhibit only doubling division, as by that alone
the permanence of species, which experience shows us to exist, is possible.
Secondly, some facts of reproduction were considered. The formation of
germinal tissues, and, in the case of lower plants and animals, the
occurrence of budding in almost any part of the body, are easily
intelligible if every cell, like the egg-cell, has been formed by doubling
division, and so contains the rudiments of all parts of the organism; and
if thus, on the call of special conditions, every cell may become a
germ-cell again.
Thirdly, great stress is to be laid on those experiments in which the
process of development was interfered with at different stages, as these
showed that the separate cells which arose by division were not predestined
unalterably for a particular _role_, according to a predetermined plan
(facts of regeneration and heteromorphosis).
Fourthly, the results of grafting, transplantation, and transfusion
indicate that the cells and tissues of an organism possess, in addition to
their patent microscopical characters, latent characters, which show
themselves to be peculiar to the species.
How does Weismann attempt to reconcile his hypothesis of differentiating
division with these facts? By the provision of different complementary
hypotheses, which, as we have seen, amount to this, that he allows the set
of rudiments which he had turned out by differentiating division of the
cell to creep in again by a back-door. He accomplishes this by his idea
that the germplasm may undergo, simultaneously, doubling and
differentiating division. In these cases cell-division has a double aspect.
According to Weismann, this is possible, because the egg contains many,
sometimes as many as a hundred, _ids_, each of which is a combination
representing the species. Weismann believes that in an egg, while it is
preparing for its first division, the _ids_ are arranged in two groups--an
active army and a reserve army. By differentiating division the active army
is broken up into the divisions, brigades, and regiments of determinants
appropriate to the separate groups of cells, and so the course of the
development is conducted according to a preconceived plan. On the other
hand, the passive, reserve army multiplies by doubling division, and is
sent along with definite parts of the active army as baggage in a fixed or
inactive condition, so that it has no influence upon the normal course of
development nor upon the characters of the cells (fixed germplasm,
inactive, accessory idioplasm, bud-idioplasm).
In spite of this purely arbitrary, complementary hypothesis, the facts seem
to me to show that Weismann assumed an untenable position when he
attributed a reserve army of 'stable plasma' only to the sets of cells in
which it was necessary to suppose its existence. The experiments of
Driesch, Wilson, and myself show that a complete embryo may spring from a
half or quarter of the egg, and that the set of nuclei first to arise may
be shifted about in the egg like a heap of billiard-balls. In the face of
such facts there seems nothing left for the theory of Weismann but to endow
every cell with accessory germplasm to prepare it for unforeseen events.
This, however, would sterilize the other part of the theory, the doctrine
of determinants, and the mechanism of development dependent on a rigid
architecture of the germplasm. Consider the confusion that would arise when
the deploying of the active army was disarranged by external influences,
now in one fashion, now in another, if the reserve army, with its store of
latent rudiments, had to come to the help of the broken pieces. What would
compel the rudiments disposed to activity according to the prearranged plan
to become latent where they were no longer wanted? And what would stir into
activity in the necessary places the originally quiescent rudiments of the
reserve army? In fact, if the _roles_ of activity and quiescence are even
once to be exchanged by the rudiments in the cell, what object is there in
drawing a distinction so sharp between the two armies--the active army
which carries out the process of development according to a plan
prearranged in its minutest details, and a passive reserve army ordered
into quiescence and carried as baggage?
But here we come upon the scarlet thread that continuously has traversed
the theory of germplasm in all its changes. Weismann attaches the greatest
importance to the distinction. The twofold nature of the process of
development is a cardinal point in his theory, linked to his doctrine of
immortality for unicellular organisms and germ-cells and mortality for
somatic cells.
Between somatic cells and reproductive cells Weismann places a gulf that
cannot be bridged. Only the reproductive cells contain real germplasm, and
only these contain the conditions for maintaining the species, as they
alone serve for the starting of new generations of development. The somatic
cells, on the other hand, are endowed only with fragments of germplasm, and
hence they are incapable of preserving the species, and are doomed to
death. The reproductive cells, like unicellular organisms, are regarded as
immortal, the somatic cells as mortal. According to Weismann, cells cannot
pass from the one category to the other.
As I see Nature, this contrast has been artificially reasoned into her.
From several reasons, I do not think that it exists. In the first place, I
consider that the facts I have given show the hypothesis of a
differentiating division of cells and germplasm to be not proven and
arbitrary. Next, the reproductive-cells must be considered as much a part
of the organism as any other tissue. Sometimes they form the greater part
of the body, as in many parasites, and, like the other tissues, they are
subject to death, unless the conditions necessary to their further
development have occurred in time. But under such conditions other
cell-complexes may have death averted from them, as, for instance, when a
slip cut from a willow-tree is planted. Thirdly, the reproductive cells are
derived from the egg-cell just in the same way as other tissue cells are
derived from it. Like tissue cells in multicellular organisms, they arise
by the specialisation of material separated from the egg-cell, and, like
every other organ, attain the position assigned them in the plan of
development in the course of the general metamorphosis of position that all
the cells pass through. Often the sexual cells, like those of other
tissues, appear at a distance of several cell-generations from the egg. The
intervening generations are specially numerous in those animals and plants
in which several sexless generations come between the sexual generations
(_e.g._, many plants, coelenterates, worms, tunicates).
I cannot agree to the existence (in Weismann's sense) of special
germ-tracks. Naturally, I do not deny that the sexual cells arise from the
egg after definite sequences of cell-divisions; but this happens in the
case of all specialised cells, such as muscle, liver, kidney, and bone
cells. The conception of special germ-tracks has no more significance than
there would be in the conception of muscle, liver, kidney, and bone
tracks. Though Weismann associates with germ-tracks the idea that germplasm
travels along them, proof of this has yet to be brought forward.
Finally, a word about the meaning of 'immortal.' In a scientific work the
word must be used in a philosophical sense. In calling a being immortal one
implies both individuality and indivisibility. This, at least, was the view
of the old philosophers, who have defined the idea of immortality. Thus
says Leibnitz in his _Theodice_: 'I hold that the souls which one day
become the souls of men existed already in the seed, that they have existed
always in organised form in the ancestors, back to Adam--that is to say, to
the beginning of things.'
In his doctrine of immortality, Weismann has not concerned himself with the
two implications--individuality and indivisibility. He calls a unicellular
organism immortal, simply because its life is preserved in the organisms
arising from it by division. The immortality of the unicellular forms
depends upon their divisibility, upon a property which, according to the
philosophical use of the word, is incompatible with immortality. According
to Weismann, one immortal organism gives rise to several immortal
organisms, but, as these are subject to destruction by external agents, the
separate individuals are mortal. The unicellular organism is not immortal
in itself, but only in as much as it may give rise to other organisms. In
this way Weismann comes in conflict with the idea of individuality, and is
compelled to transform his conception. For he says 'that among unicellular
organisms there are not individuals separated from each other in the sense
of time, but that each living being is separated into parts so far as space
is considered, but is continuous with its predecessors and successors, and
is, in reality, a single individual from the point of view of time.'
Consequently Weismann must take the same view of the germ-cells, which,
according to his theory, are immortal in the same way as unicellular
organisms, and, in the same sense, he must make a single individual of all
the germ cells arising from a single germ cell, and, with them, of all the
organisms developed out of them. Adam is immortal quite as much as
unicellular organisms, for he survives in his successors.
In brief, Weismann assigns immortality not to the unicellular individual,
but to the sum of all the individuals arising from it, all the individuals
of the same species, living contemporaneously and successively--in fact, to
the conception of a species.
In my view, what Weismann has tried to express by the word 'immortality' is
no more than the continuity of the process of development. So he himself
says in the course of a defence in which, however, he did not intend to
give up the standpoint he had taken; he wishes to imply, by the immortality
of unicellular organisms, only 'the deathless transformation of organic
material,' or 'a transformation of organic material that always comes back
to its original form again.'
Thus, Weismann himself really has implied that his distinction between
immortal unicellar organisms, immortal germplasm, and mortal somatic
cells, is a misconception. For the continuity of the process of
development, or the mode of transformation of organic material, depends
upon the continual formation and eventual destruction of newly-formed
material, but in no way implies the continuous existence of the organised
material in a state of organisation. From this point of view, the
immortality of unicellular organisms and of the germplasm breaks down, and,
above all, the artificial distinction between somatic cells and
reproductive cells. For, in the latter, the organic process of development,
with its transformation of organic material, also occurs.
Here I may give the conclusion of this division of my argument. Cells
multiply only by doubling division. Between somatic cells and reproductive
cells there is no strong contrast, no gulf that cannot be bridged. The
continuity of the process of development depends upon the power of the
cells to grow and to divide, and has already been set forth in the
sayings--_Omnis cellula e cellula, omnis nucleus e nucleo_. Whatever
novelty the doctrine of the continuity of the germplasm brings into this
saying depends upon error, and is in contradiction to known natural facts.
II. ARGUMENTS AGAINST THE DOCTRINE OF DETERMINANTS.
Weismann has united his doctrine of determinants with his assumption of a
differentiating division. He conceives that every little group of cells in
the adult body possessed of definite character and of definite position in
the body--in fact, every group of cells that is independently variable--is
represented in the egg and in the spermatozoon by a number of little
particles--the biophores--and that these, joined in a system, form the
determinants. The innumerable determinants, he thinks, are, so arranged in
the germplasm, and are endowed with such powers, that, during the process
of development, they reach, at the right time, the right place for their
expansion into cells. For instance, in the case of a mammal with
parti-coloured fur, as many architecturally arranged determinants would be
present as there were different spots and stripes in the fur, due to colour
and length of the hairs.
This chain of ideas, made sharp and definite by Weismann, has recurred
again and again in theoretical biological literature in a vague way. In my
view, it rests upon a false use of the conception of causality, and upon a
false implication given to the relation between the rudiment and the
product of the rudiment, each mistake involving the other.
Because, if its development be not interfered with, a definite egg
necessarily gives rise to a definite kind of animal, a complete identity
between the rudiment and the product, between cause and consequence, has
been assumed more or less consciously. The conception of the sequence has
been as if an organism caused its own development in a closed system of
forces, in a kind of organic perpetual motion. It has been overlooked that,
in the course of the development, many other conditions must be fulfilled,
as without them the product never would come from the rudiment.
That the same adults may come from the eggs depends upon the egg-cells, in
the ordinary course of events, being in similar conditions of anabolism and
katabolism, being affected by gravity, light, temperature, and so forth, in
the same way. Thus, when we are attempting to grasp the fundamental nature
of the course of organic development, we must not omit the part played by
these factors.
We may dwell for a moment upon this weighty point, as its significance is
commonly misunderstood.
The course of each organic development depends in the first place, upon the
absorption and metamorphosis of matter. Inorganic matter perpetually is
being turned into organic material to serve for the growth and development
of the rudiments. Thus, what in one stage of the development is mere
inorganic material, and an external condition of the development of the
rudiment, in the next stage is become a part of the rudiment. The food-yolk
of an egg, for instance, like the oxygen of the atmosphere, appears, in its
relation to the material of the rudiments, to be something supplied from
outside, an external condition of the development; yet it is continually
passing into the rudiments and altering them, even though the alteration
may be purely quantitative. From this follows the very simple inference
that during the course of an organic development external matter is always
being changed into internal matter, or that the rudiments are continually
growing and changing at the expense of the surroundings.
Now, let one reflect that the egg and the adult are two terminal states of
organised material, and that they are separated from each other by an
almost inconceivably long series of connecting, intermediate states;
consider that each stage of the development is the rudiment and the
producer of the succeeding stage, of the stage that follows, as the
consequence of it; consider that what was external in each antecedent stage
has entered the rudiment and become part of it in the succeeding stage.
Then it will be understood that it is a logical error to assume that all
the characters present in the last link of the chain of development have
their determining causes in the first link of the chain. The mistake lies
in this: in the failure to distinguish between the causes contained in the
egg at the beginning of the development, and the causes entering it during
the course of development from the accession of external material in the
various stages. As there can be no absolute identity between rudiment and
product, it is erroneous to transmute the visible complexity of the final
stage of the development into an invisible complexity of the first stage,
as the old evolutionists did, and as the new evolutionists are attempting
to do.
But there is another error in the doctrine of determinants. This is in
intimate union with the error just discussed, and, to put it shortly,
consists in attributing to a cell--and the egg and spermatozoon are
cells--the possession of characters not peculiar to cells, but resulting
from the co-operation of many cells.
The characters of an adult active organism, like a plant or an animal, are
exceedingly numerous, most varied in their nature, and essentially
different. Some characters depend upon the healthy co-operation of nearly
all the parts of the body, or of a group of organs; others are peculiar to
an organ, and may be referred to its shape, structure, position, function,
and so forth. Others, again, depend upon individual cells, or even upon
separate parts of cells. Is it really possible that all these characters,
so many and so heterogeneous, have special, material bearers in the germ,
and that these bearers are either simple biophores or determinants--that is
to say, groups of biophores?
I can conceive a cell as endowed only with the material bearers of such
characters as really belong to a cell itself. Thus, a reproductive cell
might have material particles as the rudiments for producing horn, chitin,
chondrin, ossein, pigment, or chlorophyll, or for nerve-fibrils,
muscle-fibrils; but not for producing a hair, or a separate ganglion of the
spinal cord or the biceps muscle. The rudiments for hairs, nerve-ganglia,
muscles, and so forth, must be groups of cells, for only groups of cells,
and not specially arranged groups of particles within a cell, are able to
grow into hairs, spinal ganglia, or muscles.
In a short statement, made in 1892, I said: 'The mistake into which
speculations upon the nature of organic development has led so many
investigators is this: they reflect the characters of the adult upon the
undivided egg, and so people that sphere of yolk with a system of tiny
particles, corresponding to the parts of the adult, qualitatively and in
spacial relations. But in this method of thinking, it is left out of count
that the egg is an organism which multiplies by division into numerous
organisms like itself, and that, in each stage of the development, it is
only by the mutual action of all these numerous elementary organisms that
the development of the whole organism slowly proceeds.'
Weismann himself, in a discussion of the pangenes of De Vries, has partly
shown that one cannot assume the existence in the cell of material
particles that are the bearers of qualities foreign to the nature of a cell
and transcending it. In reference to the attempt to explain zebra-striping
by pangenes, he says (_Germplasm_, English edition, p. 16): 'There can be
no "zebra-pangenes," because the striping of a zebra is not a cell
character. There may perhaps be black and white pangenes, whose presence
causes the black or white colour of a cell; but the striping of a zebra
does not depend on the development of these colours _within a cell_, but is
due to the regular alternation of thousands of black and white cells
arranged in stripes.' Again (p. 17), he says: 'The serrated margin of a
leaf, for instance, cannot depend on the presence of "serration-pangenes,"
but is due to the peculiar arrangement of the cells. The same argument
would apply to almost all the obvious "characters" of the species, genus,
family, and so on. For instance, the size, structure, veining, and shape
of leaves, the characteristic and often absolutely constant patches of
colour on the petals of flowers, such as orchids, may be referred to
similar causes. These qualities can only arise by the regular co-operation
of many cells.'
Notwithstanding so correct a declaration, Weismann himself, in his doctrine
of determinants, has fallen into the error he himself has exposed. To
represent characters of the adult due to groups of cells and organisms, he
imagines in the egg-cell, not simple particles like pangenes, but
architecturally arranged groups of particles, determinants.
No real change has been made. Conditions are reflected upon the cell that
in their real nature surpass its possibilities. With right and reason one
may adduce, against his own determinants, what Weismann has said about
pangenes, for exactly the same reasons: 'There cannot be zebra-determinants
or serration-determinants, because zebra-striping, like the serrated edge
of a leaf, is no cell character.'
The error in Weismann's doctrine of determinants may be made clearer by an
analogy.
The human state may be conceived as a high and compound organism that, by
the union of many individuals, and by their division into classes with
different functions, has developed into a form always becoming more
complicated. To carry out our comparison better, let us assume that all the
individuals united in the human state arose from a single pair. The single
pair would be the rudiment of the whole state, and would bear the same
significance in the development of the state, as the fertilised egg bears
to the development of the adult. The characters of the state, its different
organisations for protection, for tilling the soil, for trade, for
government, and for education, must be explained causally from the
characters of the first pair, which we take as the human rudiment, and from
the outer conditions under which that pair and the generations that arose
from it had to live.
As the state develops, urban and district communities, unions for husbandry
and manufactures, colleges of physicians, parliaments, ministries, armies,
and so forth, appear. All this visible complexity depends upon individuals
associated for definite purposes and specialised in different directions.
It would certainly not occur to anyone to explain the growth of this
complexity in the developing state by the assumption that this secondary
complexity was preformed as definite material particles present in the
first pair, although the first pair is the rudiment of the whole. Much
comment is unnecessary; everyone must feel that this attempt to explain the
causal relations is on the wrong track, that it is perverse to try to
explain the complex characters of the human state by a system of
architecturally arranged particles stored within the first pair. The
organisations arising from the co-operation of many men are something new,
and cannot be regarded as present in the organizations of one man. No doubt
they depend, in the last resort, upon human nature, but by no means in this
crude, mechanical fashion.
But what applies to the causal relations between the state-organism and men
applies also, _ceteris paribus_, to the explanation of the causal relations
between the rudiments in the egg and the organism to which the egg gives
rise. For these an explanation cannot be expected on the lines of
Weismann's doctrine of determinants, as that implies a fundamentally
erroneous assumption. It refers organizations that depend upon
cell-communities to organizations of material particles within a cell.
'To understand inheritance,' says Naegeli, with truth, 'we require not an
independent, special symbol for every difference resulting from time,
space, and quality, but a substance that, by the linking of the limited
number of elements in it, can exhibit every possible combination of
differences, and that by permutation can pass into another combination of
differences.'
This standpoint is clearer when interpreted in terms of cells. The
hereditary masses contained in the egg and spermatozoon can be composed
only of such particles as are the bearers of cell-characters. Every
compound organism can inherit characters only in the form of
cell-characters. The innumerable, and endlessly variable, characters of
plants and animals are of composite nature. They find their expression in
differences of shape, structure, and function in the organs and tissues,
and in the special methods in which these are interrelated. They depend
upon the co-operation of many cells, and, for this reason, cannot be
carried into the hereditary mass of any cell by material bearers. They are
secondary formations, that can arise only after the multiplication of
cells, and from the varied combination of cell-characters that accompanies
the multiplication of cells.
In the foregoing pages I have attempted to prove the untenability of the
doctrine of determinants from general considerations. I shall now attempt
the same by analysis of a concrete case. The frog's egg may serve for this.
It is a familiar object, frequently studied. Consider its mode of division,
and the formation of the blastula, gastrula, and germinal layers.
In cleavage the nucleus plays the chief part, and thus has been accepted as
the bearer of the hereditary mass. But no single, special determinant gives
the impulse for cleavage; rather, the co-operation of all the particles
that are essential to the nature of the nucleus. The chromosomes, which we
may regard as independently growing and dividing units, must have doubled
by assimilation of food material from the yolk; perhaps, also, the
centrosome may have doubled in the same way before the nucleus is in a
condition to divide. This condition itself appears the necessary result of
many different processes of nutrition and growth, as the result of
complicated chemical processes that run their course within the separate,
elementary, vital units of the nucleus.
The multiplication of the nucleus into two, four, and eight
daughter-nuclei, and so forth, gives the impulse for the breaking up of the
yolk into a corresponding number of cells. In that process the direction
of the cleavage-planes, the relative positions and the different sizes of
the cells exhibit, under normal conditions, the most marked regularity. But
it may be shown directly that this regularity is not the result of special
determinants lying within the nucleus. For all these phenomena, which are
characteristic in the cleavage of the frog's egg, as well as in the
cleavage of all other eggs, are determined directly by the qualities of the
yolk surrounding the nucleus.
In several publications I have shown clearly that the external form of an
egg and the arrangement of its contents, according to the different
specific gravities of the component particles, determine the position of
the nucleus and of the successive planes of division. Similarly, the
different sizes of the cells first formed and the unequal rate of division
shown at the two poles of the egg depend upon the constitution of the yolk,
upon the cleavage of the yolk into a portion richer in protoplasm and a
portion poorer in protoplasm, and upon the differences in the bulk of
protoplasm that in this way reaches each of the first-formed cells.
In many cases it has been shown that there is a constant relation between
the first three cleavage-planes of the egg and the long axis of the animal
that arises from the egg. Weismann and Roux make this a proof that, in
nuclear division, the nuclei that arise have different qualities; that the
protoplasmic masses lying to the right and left of the median plane are set
apart to build up the right and left halves of the embryo; that,
similarly, the first transverse and horizontal cleavage-planes divide the
protoplasm of the egg into pieces predetermined for the formation of the
anterior and posterior, dorsal and ventral, parts of the embryo.
But I think I have shown beyond possibility of doubt that these events are
due not to the existence of special, mysteriously working groups of
determinants within the nucleus, but merely to the specific shape of the
whole egg and to the segregation of the yolk. It is self-evident that, as
the body of the embryo builds itself up from the actual material of the
egg, the way in which the material of the egg is disposed must be of great
influence upon the formation of the shape of the embryo. And so, in a
recently published work, I stated that the growing embryo, especially in
its early stages, must conform in many ways to the shape of the fertilised
egg.
Thus, to bear out what I have been saying by actual examples, the
distribution of the actual particles of the fertilised egg must correspond
to the disposition of the bulk of material in the blastosphere; for, in the
breaking up into cells, the spacial arrangement of the substances of
different weights undergoes no change. Thus, amphibia, the eggs of which
have the poles different in character, produce blastospheres the poles of
which are unlike; while eggs, like those of the fowl, where the yolk does
not divide, give rise to blastospheres with unsegmented yolk. In such cases
the more or less complete segregation of the yolk and gravity, which causes
a separation of the contents of the egg according to the weights of the
particles, are agencies determining the particular kind of development. It
is no case of special groups of determinants within the nucleus.
Thus, an oval and an elongate egg produce respectively an oval and an
elongate blastosphere. The blastosphere determines the orientation of the
gastrula, and so forth. In fact, the original distribution of mass in the
material of the egg is carried directly on to the following stages of
development (oval eggs of triton, insects, etc.).
So, finally, in many eggs, where, in addition to a polar differentiation,
there is also a bilateral symmetry in the distribution of substances of
different specific gravities and of different physiological value, the
resulting blastospheres, from the reasons given above, assume a bilaterally
symmetrical form.
Although, then, in eggs with polar differentiation, which have either one
axis longer or are bilaterally symmetrical, under normal conditions the
planes of the first two segmentations may correspond to the principal axes
of the future embryo, the cause for this agreement lies in the structure of
the egg, and is not to be looked for, as Roux and Weismann suppose, in
differentiating processes of cleavage, undergone by the nuclei in their
first divisions. It is in this way that there are to be explained the
investigations made by Van Beneden and Juelin upon the eggs of ascidians, by
Wilson upon the egg of _Nereis_, by Roux upon the egg of _Rana esculenta_,
and by me on the egg of _Triton_.
As it fails with the process of cleavage, so Weismann's doctrine of
determinants fails when we analyse the formation of the blastosphere, the
gastrula, and the germinal layers.
The formation of the blastosphere seems to me to be due to the co-operation
of the following processes:
(1) In the division of the egg-cell cavities arise between the four, eight,
and sixteen pieces, and thus the whole contents of the egg become arranged
more loosely. (2) The more the cells multiply by division and become
smaller in circumference, the more closely they apply their lateral
surfaces to each other, especially at the outer surface of the whole, so
assuming the arrangement of cell-epithelia. (3) By the secretion of fluid,
a constantly growing central cavity is formed _pari passu_ with the
approximation of the superficial cells, and this probably also brings with
it an increase of the internal pressure, and a wider curvature of the wall
of the sphere.
Now, is there any part of these processes that has to do with the breaking
of the nuclear contents into groups of determinants with different
qualities? By no means. The egg divides into many pieces, because such
division is a general property of cells, and it is not associated with
separate, special material bearers. The appearance of spaces between the
cells, resulting from division, is due to forces some of which reside
within the single cells, some of which come from without. In especial, the
assumption of a spherical shape--an assumption occurring also to a greater
or less degree when the results of division leave each other--is caused by
the yolk actively arranging itself round the two nuclei as centres of
attraction. The attempt to become spherical is opposed by other forces, in
accordance with which the cells resulting from division press against each
other. These forces that press the cells together seem to increase, as the
size of the cells diminishes, so that the cells approximate their lateral
faces continually more closely. The secretion of fluid into the interior of
the sphere and the resulting increase of the outer surface results from the
characters of the whole wall, and cannot be explained by single, specially
determined cells.
Finally, to take the case of the special kinds of blastospheres (_e.g._, of
amphioxus, amphibia, reptiles, birds, and so forth), it has been already
shown that these are produced by the shape of the egg, by the bulk of the
yolk, and by the segregation of the yolk-particles under the influence of
gravity; that, in fact, the shapes are determined by the general gross
conditions of the structure of the egg.
Plainly, the blastosphere cannot be pre-existing as a structure of
particles in the fertilised nucleus; there cannot be blastosphere
determinants. The conditions for the origin of the blastosphere come into
existence only by the process of segmentation, and it is only by its
capacity to divide that the egg contains the conditions for blastosphere
formation. Here we have epigenesis--the appearance of a new formation, not
the becoming visible of pre-existing complexity.
The conditions of gastrulation and of the formation of the germinal layers
are similar. The invagination of the blastosphere comes about by the
co-operation of all the cells of its wall, by local differences in the
rates of growth in that wall, from dissimilarities in its curvature, from
many causes which have not yet been sufficiently sought out and
investigated. As cell division itself depends not upon special particles,
but upon changes in the entire nuclear contents, it follows that the growth
of the blastosphere-wall, which is merely the sum of the growth of all the
cells in it, cannot be determined by special groups of determinants.
As an attempt to explain gastrulation, the origin of the germinal layers
and many other events of development, the doctrine of determinants has
reversed cause and effect. Certain cells do not become invaginated into the
segmentation cavity because they possess groups of determinants that impel
them to the assumption of inner layer characters. The reverse is the truth.
Local conditions of growth cause the invagination of a set of the cells of
the blastosphere-wall. This invaginated layer of cells, brought into a new
position with regard to its environment, becomes the endoderm and receives
the stimulus to assume the character appropriate to the new environment. It
is unlogical to speak of endoderm in the fashion of many textbooks and
treatises on embryology, while the so-called endoderm cells still form part
of the outer surface of the blastosphere, or even while they are still in
process of formation by cleavage. For 'inner germinal layer' implies a
condition of position which is created by the invagination.
In fact, it is impossible, in thinking of the gastrula as in thinking of
the blastosphere, to conceive that in the egg, which is a simple cell,
there can be preformed by material particles in the nucleus a condition
which implies the existence of two layers of cells.
Thus analysis of a special case leads to the same conclusion as is reached
by the general reasoning of the earlier part of this section.
FOOTNOTES:
[7] _The Germplasm_, pp. 68, 69.
[8] The following treatises contain criticisms of Weismann's theories: W.
Haacke, _Gestaltung und Vererbung_; Leipzig, 1893; Herbert Spencer,
articles in _Contemporary Review_ (1893-94); Romanes, _An Examination of
Weismannism_; Longmans, 1893.
[9] Notwithstanding the objections raised by Bergh, Verworn, and Haacke, I
abide by the supposition that the nucleus of reproductive cells contains
the hereditary mass or germinal material. My reasons may be found in my
text-book on _The Cell_ (English edit., p. 274). Briefly they are: 1. The
equivalence of the male and female hereditary masses. 2. The equal
distribution of the growing nuclear mass of the primary egg-cell among the
daughter-cells that, arising from it, build up the organism. 3. The
preservation of a constancy of bulk of the hereditary mass when
fertilization occurs. 4. The isotropism of protoplasm. Following Pflueger, I
mean by isotropism that the protoplasm of the egg does not contain local
areas for the formation of different organs; but that, according to the
conditions, any part of the protoplasm may be employed in the formation of
any organ. Isotropism is merely the negation of His' doctrine of the
presence of local areas for definite organs, and without losing its
meaning, is compatible with the fact that many eggs have their poles
different, and that others have a bilateral symmetry which determines the
plane of the first division. 5. The fact that the first stages of many
embryonic developments consist in the multiplication of the nuclear
material and its distribution in the yolk, following which the yolk-mass
cleaves into cells.
[10] English edition, p. 32.
[11] English edition, p. 34.
[12] In this section upon heteromorphosis I rely upon the following
treatises, which have appeared recently. Loeb, _Untersuchungen zur
physiologischen Morphologie der Thiere. Organbildung und Wachsthum_. Heft,
1 and 2 (1891-1892). H. de Vries, _Intracellulare Pangenesis_ (1889). H.
Driesch, _Entwicklungsmechamische Studien_, i.-vi.; _Zeitschrift f.
wissenschaft, Zool._, vol. liii.-lv. The same, _Zur Theorie der thierischen
Formbildung._ _Biol. Centralblatt_, vol. xiii., 1893. Chabry, _Contribution
a l'embryologie normale et teratologique des Ascidies simples. Jour. de
l'Anat. et de Physiol._ (1887). Wilson, _Amphioxus and the Mosaic Theory.
Journal of Morph._ (1893). See also _Anatomischer Anzeiger_ (1892).
[13] Roux tried to give experimental evidence in favour of his mosaic
theory in a treatise _On the Artificial Productions of Half-Embryos by the
Destruction of one of the first two Cleavage-Cells, and on the
Reconstruction of the Lost Parts_. _Virchow's Archiv._, vol. cxiv., 1888.
Roux defends his mosaic theory against Driesch and myself in (1) _Ueber das
entwicklungsmechanische Vermoegen jeder der beiden ersten Furchungszellen
des Eies. Verhandl. der Anat. Gesellsch. der 6'ten Versamml. in Wien_,
1892. (2) _Ueber Mosaikarbeit und neuere Entwicklungshypothesen._
Anatomische Hefte von Merkel und Bonnet (1893). Also in _Biol.
Centralblatt_ (1893); in the _Anatom. Anzeiger_ (1893), and in the treatise
_Die Methoden zur Erzeugung halber Froschembryonen und zum Nachweis der
Beziehung der ersten Furchungsebenen des Froscheies zur Medianebene des
Embryo. Anatom. Anzeiger._ (1894); Nos. 8 and 9.
If, as would appear from the last treatise, Roux would avoid being reckoned
with evolutionists, he must abandon his mosaic theory, and this he has not
done. I think in the present essay, on theoretical and experimental grounds
I have shown the untenability of Roux's mosaic theory.
[14] The terms vertical and horizontal refer to the vertical axis of the
egg, which passes through the animal and vegetative poles.--_Translator's
note._
[15] Further details concerning these experiments may be found in HERTWIG,
_Ueber den Werth der ersten Furchungszellen fuer die Organbildung des
Embryo_. Experimentelle Studien am Froschund Tritonei. _Archiv. fuer
Mikrosk. Anatomie_, vol. xlii., 1893, p. 710; Plate xli.; Figs. 1, 2, 27.
[16] For the facts in this section I rely in particular upon the writings
of Voechting, Bert, Ollier, Trembley, Landois, Ponfick, and others:
H. VOeCHTING: _Ueber Transplantation auf Pflanzenkoerper_. _Untersuchungen
zur Physiologie und Pathologie_; Tuebingen, 1892.
VON GAeRTNER: _Versuche und Beobachtungen ueber die Bastarderzeugung im
Pflanzenreich_, 1849.
LEOPOLD OLLIER: _Recherches experimentales sur la production artificielle
des os au moyen de la transplantation du perioste, etc._ _Journal de la
physiologie de l'homme et des animaux_, tom. ii., 1859, pp. 1, 169, 468.
LEOPOLD OLLIER: _Recherches experimentales sur les greffes osseuses_. The
same, tom. iii., p. 88, 1860.
PAUL BERT: _Recherches experimentales pour servir a l'histoire de la
vitalite propre des tissus animaux_. _Annales des Sciences naturelles, Ser.
V., Zoologie_, tom. v., 1886.
VON RECKLINGHAUSEN: _Die Wiedererzeugung (Regeneration) und die
Ueberpflanzung (Transplantation)_. _Handbuch d. Allgem. Pathologie des
Kreislaufs aus Deutsche Chirurgie_, 1883.
TREMBLEY: _Memoires pour servir a l'histoire d'un genre de Polypes d'eau
douce_, 1744.
LANDOIS: _Die Transfusion des Blutes_; Leipzig, 1875.
ADOLF SCHMITT: _Ueber Osteoplastik in klinischer und experimenteller
Beziehung_. _Arbeiten aus der chirurgischenklinik der Koenigl. Universitaet,
Berlin._
PONFICK: _Experimentelle Beatraege zur Lehre von der Transfusion_.
_Virchow's Archiv._, vol. lxii.
BERESOWSEY: _Ueber die histologischen Vorgaenge bei der Transplantation von
Hautstuecken auf Thiere einer anderen Species_. _Ziegler's Beitraege zur
pathologischen Anatomie und zur allgemeinen Pathologie_; Jena, 1893.