Regeneration

by Thomas Hunt Morgan

Bonnet takes care to state that the pre-formed germs may not appear to us like miniature copies of the part into which they develop, but they are so constructed that, as they absorb nourishment and become larger, they assume a characteristic form.

Weismann, who has also accepted the pre-formation hypothesis to account for the development of the egg, has applied the same conception of pre-formation to the process of regeneration. He believes that partial, latent germs are present in different parts of the body, and that these germs are present especially in animals that are liable to injury and in those parts of the body that are likely to meet with accidents. In these essential respects, Weismann’s idea is the same as Bonnet’s; but in regard to the location of the germs, and their manner of awakening, and as to how the forms, liable to injury, have acquired their power to regenerate, Weismann adopts more modern standards. He believes that the germs are located in the nucleus. Those that bring about the development of the egg are supposed to be different from those that bring about regeneration, because the method of regeneration is generally different from the method of development of the egg.

Regeneration, on Weismann’s view, is brought about by latent cells containing pre-formed germs in the chromosomes of the nucleus. These germs are called the determinants. Since at each level in an animal, or in a part of an animal, regeneration may occur and replace the missing part, it is assumed that the germs are correspondingly different at each level, and represent all the parts that lie distal to that region. Weismann does not suppose that there is a single germ at each level that represents all the distal parts, but that in each layer, or organ, or part there are many cells that contain germs corresponding to the distal regions. The qualities of the latent cells are sorted out by means of the qualitative divisions of the chromatic material of the nucleus. Moreover, since the new part can itself regenerate, the further assumption is made that during regeneration new subsidiary or latent cells are laid down at each level. This is supposed to be brought about by a quantitative division of each germ after it has reached its definitive position in the new part.

Weismann’s general attitude toward the problem of regeneration is summed up in the following statements: “It may, I believe, be deduced with certainty from those phenomena of regeneration with which we are acquainted, that the capacity for regeneration is not a primary quality of the organism, but that it is a phenomenon of adaptation.” Again, “Hence there is no such thing as a general power of regeneration; in each kind of animal this power is graduated according to the need of regeneration in the part under consideration.” “We are, therefore, led to infer that the general capacity of all parts for regeneration may have been acquired by selection in the lower and simpler forms, and that it has slowly decreased in the course of phylogeny in correspondence with the increase in complexity of organization, but that it may, on the other hand, be increased by special selective processes in each stage of its degeneration in the case of certain parts which are physiologically important and at the same time frequently exposed to loss.”

The evidence brought forward in the preceding pages leads, I think, to precisely the opposite conclusions, and, in certain cases at least, it has been shown that there can be no relation between the power of regeneration and the extent of exposure of a part to injury or to loss. It is unnecessary to enter here further into this question, since it has been discussed already in Chapter V.

Weismann’s statement that the power of regeneration has decreased “in correspondence with the increase in the complexity of the part” cannot by any means be entirely accepted. If the complexity of a part is of such a kind that the part cannot sustain itself independently until regeneration has taken place, or if the exposed surface of the wound is such that it cannot be closed over, or if the new part cannot be properly nourished, or if the tissues have changed in such a way that their cells can no longer multiply, then the statement is, to a certain extent, true. On the other hand, when we find that one of the most complicated organs of the body, the eye, can regenerate in the salamander, if only a piece of the optic cup is left attached to the nerve, we may well doubt if there is any such direct and general connection between regeneration and complexity as Weismann maintains.

Weismann’s so-called “mechanism” of qualitative nuclear division is the basis of his conception of pre-formation. We are, I think, at present in a position to reject not only this conception, since it finds no support either in observation or experiment, but also his view that regeneration is brought about by latent cells; for it has been shown in a large number of cases that the new cells come directly from the old, differentiated ones. In a previous chapter it has been pointed out that Weismann’s idea that regeneration has been acquired by a process of natural selection, and is under the influence of this supposed agent, is in direct contradiction to a number of known facts. Under these circumstances we are warranted, I think, in concluding that the entire Weismannian point of view is wrong.

The process of regeneration has been often compared to the process by which a broken crystal completes itself. Herbert Spencer, in particular, has elaborated this idea. In his book on the Principles of Biology, he says: “What must we say of the ability an organism has to recomplete itself when one of its parts is cut off? Is it of the same order as the ability of an injured crystal to recomplete itself? In either case new matter is so deposited as to restore the original outline. And if, in the case of a crystal, we say that the whole aggregate exerts over its parts a force which constrains the newly integrated molecules to take a certain definite form, we seem obliged, in the case of the organism, to assume an analogous force.” Spencer has called attention to a superficial resemblance between the renewal of a part of a crystal and the regeneration of an animal, and without further inquiry into the profound differences between the processes, assumes that “analogous forces” are at work. Now that we know something more of both processes, we find so much that is totally different, that there remains no basis for Spencer’s conclusion, namely, that analogous forces must be present. Furthermore, Spencer’s statement that the whole crystal aggregate exerts over its parts a force of some kind is diametrically opposed to our idea as to the method of “growth” of a crystal in a saturated solution. The new material is added always at the surface of the crystal, and the growth of each point is self-determining. There is no central force that controls the deposition of new material in the different regions. Rauber’s work on the so-called regeneration of the crystal has given us a clearer conception of how the process is brought about. He has shown that when a piece is broken from a crystal, and the crystal suspended in a saturated solution of the same substance, it becomes larger by the deposition of new material over all its surfaces. The addition of new material may be more rapid over the cut-surface than elsewhere, but it must not be supposed that the more rapid “growth” takes place in order to complete the form of the crystal, for the growth over the cut-surface follows precisely the same laws that regulate the “growth” over all the other surfaces, that is taking place at the same time. In this respect we find an essential difference between the regeneration of a crystal and that of an animal, since in the latter the growth takes place only over the cut-surface; and, in forms that regenerate by proliferation, at the expense of the old material, so that the old material is correspondingly diminished as the new part grows larger. Regeneration may even take place in an animal deprived of all food, and also in one that is starving to death and diminishing in size. In those forms that regenerate by a change in shape of the entire piece into that characteristic of the typical form, the process bears not even the remotest resemblance to the process in the crystal. It is so obvious from every point of view that the comparison is entirely a superficial one, that it seems useless to point out further differences between the two processes.

Pflüger (’83) has given, in brief outline, an hypothesis to account for the process of regeneration. He states that since there is always replaced exactly what is lost, the new part cannot arise from a pre-existing whole germ. If, for instance, the leg of a salamander is cut off at any level, as much comes back as is removed. The assumption of a leg germ is insufficient to account for the fact that only as much comes back as is lost, and not always a whole leg. Pflüger, therefore, offers another hypothesis. He assumes that food material is taken up at the wounded surface and organized into the substance of the new part. The new material is laid down at the surface of the old material, and is then organized into the kind of tissue that lay just beyond that region in the whole limb. Upon this first layer a new layer is deposited that is organized into the next part of the limb, and so on, until the whole missing part is replaced. Pflüger does not give any idea of how the new material is deposited at the cut-surface, but from what we know of the histology of the process we must suppose, if we should adopt Pflüger’s interpretation, that new cells are produced by the old ones, and that these new cells form the successive layers out of which the new limb is produced. Pflüger speaks of an arranging molecular force, which we can only suppose, in the light of what has just been said, to act from cell to cell through the continuous protoplasm. Pflüger also pointed out that in certain cases the organization can take place only in a certain direction, that is, in some forms regeneration can take place from one side of a cut-surface, but not from the other. He interprets this as due to a polarization of the protoplasm, one surface having peculiarities that are absent in the other.

There are certain objections to Pflüger’s hypothesis that suggest themselves. In the first place the new part does not, in many cases, replace all that has been removed, and hence it is difficult to see how the building up in the way Pflüger supposes, could take place. In these cases the new material forms only the distal end of the part removed, and the relation of the old to the new part is of secondary importance. Again, in cases of heteromorphosis, as when a tail develops on an anterior cut-surface of a piece of an earthworm, the result must be due to quite different factors from those suggested by Pflüger. The results are, in fact, the reverse of what the hypothesis demands. Furthermore, when the entire piece is transformed into a whole new organism, there is very little in the process to suggest a change like that postulated by Pflüger. On the other hand there cannot be much doubt that the old part may have some influence, and in certain cases a very important influence on the new part, but whether this is a purely molecular influence is open to doubt. In whatever way this influence may act, it is only one of a number of factors that take a share in the result. The amount of new material, that is formed before the organization of the new part begins, seems to be also a factor; and the one that determines how much of the missing part can be replaced, and this in turn seems to be connected with the lowest organization size that can be produced. The distal end of the new part forms always the distal end of the organ that is to be produced. If enough new material has developed (before the organization of the new part takes place) to produce all of the missing part, the latter is formed, but if the material is insufficient to produce the whole structure, then as much of the distal end as possible is formed. In some cases, as in the planarians, the missing intermediate regions may subsequently develop behind the distal part that is first produced.