Regeneration

by Thomas Hunt Morgan

This analysis shows, I think, that the transformation of a piece into a new whole really involves a change in the fundamental structure itself. There cannot be much doubt that both the polarity and the bilaterality of the egg, or of a piece of the egg, belong fundamentally to the same class of phenomena, and we are forced to the supposition that they are inherent peculiarities of the living substance. Driesch thought at one time that it is only necessary to suppose that the protoplasm, and every part of it, possesses a primary polarity, and that some inequality in the material might determine the plane of bilaterality; but later he thought it necessary to assume also the presence of a bilateral structure in the protoplasm, and in all parts of it. This assumption of every part having a polar and a bilateral structure, and the polarity and bilaterality of the whole being the sum total of those of all its parts, is, I think, insufficient to meet the situation. If, for example, the first plane of cleavage coincides with the median plane of the body, the right blastomere has a structure that leads to the formation of the right side of the body, and similarly for the left blastomere. If the two blastomeres are separated, and each gives rise to a whole embryo with a new plane of bilateral symmetry, we must suppose that a new bilaterality has been produced. It does not make the problem any simpler to assume, as Driesch has done, that this is brought about by the elements rearranging themselves bilaterally on each side of a new plane that passes through the middle of the isolated blastomere, for what we need to have explained is what determines the new median plane. It seems to me that the problem is not any simpler, if we assume the polarity and bilaterality to be the property of a large number of elements, as Driesch has done, than if we assume at once the polarity and bilaterality as characteristic of the whole egg. The difficulty of understanding how a new bilaterality can be induced in a piece of the whole is as great on the one assumption as on the other. Not only is it, I think, a much simpler idea to suppose the structure is something pertaining to the whole and is not the sum total of smaller wholes, but the idea is more in accord with other phenomena.

We meet here, I think, with precisely the same problem that we meet with in the regeneration of parts of adult animals. If a planarian is cut in two lengthwise, along the middle line, each half produces new tissue at the cut-side, out of which the missing half is formed. In this case the old median plane remains, more or less, as the median plane of the new worm, i.e. the structure of the new part is built up on that of the old. Very much the same result follows when the worm is cut longitudinally into two unequal parts. The larger piece retains its old plane of symmetry and adds to the cut-edge a new part that completes the symmetry. The smaller piece also builds up new material along the cut-edge, and a new plane of symmetry is formed between the old and the new parts. Here, also, a median plane is established at the edge of the old material, but in this case the material lay to one side of the old middle line, and this involves the changing over to a large extent of the old material, so that it fits in with the new structures of the new median plane.

In those forms in which the readjustment takes place entirely in the old part, the change of conditions is more difficult to interpret. In some respects hydra gives us an intermediate condition, but since it is a radially symmetrical instead of bilaterally symmetrical form, the transformation is not so obvious. If a cylindrical piece is cut from the body, and is then cut lengthwise into two half-cylinders, each closes in and makes a cylinder of smaller diameter. A little new tissue may appear along the fused edges, but the missing half is not replaced, and a new hydra with a body of half size is formed from the piece. It is to all appearances a radially symmetrical form, and we must think, in this case, of the new axis of symmetry as having shifted to the middle of the piece. As yet no similar experiments have been made on a bilateral animal that regenerates by morphallaxis, so that we have nothing to appeal to for comparison with the bilateral egg, but the results, just described for the planarian and for hydra, indicate how a change might take place in pieces of adult animals that would lead to the formation in them of a new symmetrical structure. If we imagine a case of this sort, and suppose that after separating a piece from the side the cut-edge closed in and the piece assumed a symmetrical form, it is conceivable that a new plane of bilateral symmetry might soon appear in the middle of the piece owing to the symmetrical form of the piece; or the new plane of symmetry might slowly shift from the cut-edge toward the middle of the piece, after reaching which the balance or equilibrium would be attained. This statement, it must be confessed, is little more than a supposition, and rests on the unproven assumption that the internal symmetry may develop in response to a symmetrical change in shape of the piece as a whole, which is partly the outcome of purely physical factors. At present, however, I see no other probable inference from the facts.

If we suppose a bilateral structure is present in the fertilized egg, and that it corresponds to the first plane of cleavage, a change of the sort that we have just sketched above may be supposed to take place when the blastomeres are separated. The stimulus is found in the new spherical form assumed by the isolated blastomere, and we may imagine the change to take place, in the way indicated, by virtue of the old bilaterality that is present, the change beginning at the side originally in contact with the other half.

There are several facts which seem to indicate that a change in the axial relations of the egg is very easily brought about before any definite organs have appeared. The fact that the point of entrance of the spermatozoon in the egg of the frog[127] and of the sea-urchin[128] may determine the first plane of cleavage points to this conclusion. The fact that, in the frog, and also in the triton, the median plane of the embryo corresponds sometimes to the first, sometimes to the second plane of cleavage, and sometimes to neither one, shows that the bilaterality of the embryo-structure may or may not coincide with the plane of cleavage. In the fish also there seems to be no correspondence between the planes of cleavage and those of the embryo, so that different factors may determine the two. We should not be justified in concluding from this evidence that a bilateral structure is absent, but rather that it is of such a sort as to be independent of the cleavage, and that it can be also easily changed. It is probable that the kind of organization that we must suppose to exist in the egg is of a very simple sort, and capable of easy readjustment. There is certainly no evidence in favor of the view that the organization of the egg need be anything like the organization of the embryo that comes from the egg, although the organization of the egg may be perfectly definite in its character. Until we know more of the nature of this organization, it is useless to speculate further as to how it can be altered.

Another question of much importance in connection with our present topic is the part played by the individual cells in the early development of the whole egg, or of any part of the egg. Hertwig (’93) thinks that the development is brought about by the action of the individual cells on each other. Driesch, when he states that the fate of a blastomere is a function of its position in the whole, does not commit himself definitely one way or the other so far as the cell as a unit is concerned. Whitman and others have urged the insufficiency of the cell theory, and think that cell boundaries play no important part in the development, but that the embryo develops as a whole. This has seemed to me to be the more probable view in the light of certain results of experimental embryology. Driesch, in later papers, has also opposed Hertwig’s idea, and Wilson in his book on The Cell has also, to a certain extent, adopted this point of view. The formation of a typical larva in the sea-urchin and in amphioxus out of one-half or one-fourth the whole number of cells demonstrates, I think, the insufficiency of the cell-unit hypothesis. The discovery of continuous protoplasmic connections between neighboring cells, and the formation of new protoplasmic connections between all regions, as found by Mrs. G. F. Andrews,[129] gives us a basis of fact on which to rest the hypothesis of the embryo being a whole structure. This view meets with no great difficulty on the grounds that the nuclei are distinct centres of metabolic activity, for we know at present so little of what sort of action takes place between the nucleus and the protoplasm that we cannot rest our argument on any demonstrable relation.

The discovery that pieces below a certain minimum size are incapable of producing a whole organism is of capital importance. It has been pointed out that pieces of the egg of the sea-urchin less than one-sixteenth of the whole do not produce even the gastrula stage. In amphioxus the one-eighth blastomere seems to be near the lower limit of development. It has also been found that there is a lower limit for pieces of adult organisms below which they do not regenerate. This has been shown for hydra, tubularia, planarians, and stentor, and is probably true for all forms. This result is especially interesting in those cases in which the parts contain all the elements necessary to produce a new organism, and come from parts of the body that are totipotent in these respects. It seems certain that the lack of power of development in these cases is due entirely to the smallness of the piece. We can express the idea in another way by stating that a certain volume is necessary in order that a piece may produce the typical organization. This conclusion is important as showing that the organization is something enormously large as compared with the size of the chemical or physical molecules, and even of the crystal molecule. The size of a piece that is at the lower limit of organization is also very much larger than the smallest cells of which the embryo is made up, and this relation is a point in favor of the view that the organization is not simply the resultant of the interaction of the cells, but is something much larger than these cells; and we may even go further, I think, and add that it dominates the cells rather than is controlled by them.

In the light of the questions discussed in the preceding pages, we may now attempt to follow out in a more connected way some of the modern views and hypotheses dealing with the problem of development.

Hertwig, as we have seen, has opposed the Roux-Weismann hypothesis, and has formulated a view of his own. According to Hertwig, the cleavage divides the egg into equivalent parts,—an idea very similar to that of Pflüger. The cells he regards as units, and the development as the result of the interaction of the cells,—a process that in a way Roux had also assumed to take place between the different parts of the later embryo. Thus, while Hertwig’s hypothesis contains little that is really new, it has selected portions from several already existing hypotheses, and united them into a consistent whole. It has been objected to Hertwig’s view that the interaction of equivalent cells could never account for the introduction of new processes in the development; but if we grant that the cells are never entirely equivalent, whatever their potence may be, this objection can, I think, be met. Hertwig’s chief service has been his destructive criticism of the Roux-Weismann idea of qualitative nuclear division.

Hertwig maintains that each stage in the development is the cause of the next stage, and states that a description of the series of stages through which the embryo passes gives a causal knowledge of the phenomena of development. He claims that beyond this descriptive knowledge we cannot hope to penetrate. Both Roux and Driesch have taken issue with Hertwig, and have pointed out that while each stage in the development contains within itself the causes of the succeeding stage, yet we gain no idea as to these causes from a simple description of two consecutive stages themselves. To state that the fertilized egg is the cause of the cleavage gives us no idea of what sort of a process the cleavage is, or how it arises, or what determines the sequence of the divisions, etc. The blastula, for instance, contains the factors that produce the gastrula; but to state that, in a physical sense, the blastula is the cause of the gastrula is an erroneous interpretation of what is meant by causal knowledge. If Hertwig’s idea were correct, there would be as many causes in each embryo as there are stages in its development, and as many causes in the whole range of embryology as there are forms that develop multiplied by the number of stages in each embryo. What we should seek to discover is the particular cause that brings about each kind of process. If we could discover the cause in one single case, it is highly probable that it would be found to extend to a large number of other cases.