Regeneration

by Thomas Hunt Morgan

If it be admitted that the same factors that affect the growth also affect in the same way the regeneration, we have made a distinct advance. It is, moreover, not difficult for us to understand how this is possible. If we consider first those cases in which growth takes place at one or more points at which the cells are undifferentiated, and compare this condition with that in regenerating animals that produce new tissue by proliferation, we can picture to ourselves that the same factors would act on the undifferentiated tissue in the same way in both cases. This does not explain what causes the organism to produce the new cells that appear over an exposed surface, and we must search for other factors to account for the out-wandering of cells, and for the local multiplication of the cells at the cut-end. We find a parallel to those cases in which the growth of an organism takes place throughout the whole body, in those animals in which the regeneration also takes place in the old part. This comparison should not, however, be pushed too far, since, in some forms, as, for example, a salamander, the growth of the animal takes place throughout the body, while regeneration takes place by the proliferation of new material. The difference in the regenerative process in a salamander and in a form like hydra is not due so much to the inability of the old cells of the salamander to increase in number as compared with those of hydra, but rather, it appears, to a certain rigidity or stiffness of the body of the salamander that prevents the rearrangement of the parts; and the recompletion of the form takes place in the direction of least resistance, i.e. at the open or cut-end of the body.

Regeneration by means of morphallaxis takes place only in those forms in which the body is not made up of a series of separated parts. This kind of regeneration occurs in those organisms in which the normal growth consists only in the enlargement of a system of organs already present. A piece of an animal of this sort usually contains the elements of each kind of organ, and from these the new parts are produced, both by proliferation at the cut-ends and by the enlargement of the parts that are present in the piece. In forms with separate segments we find, in some cases, resemblances between normal growth and regeneration, as shown, for example, in the earthworm. There is present in the young worm a region in front of the last segment, or, rather, a part of this segment, from which new segments are formed. In the regeneration of the posterior end a knob of new tissue is formed, and out of this a few segments develop, the last one having a growing region similar to that in the young worm. The subsequent stages in the regeneration involve the formation of new segments from the last one, as in the young worm. There is no such growing zone at the anterior end of the young worm, and none is formed in the regeneration of an anterior end, so that only the segments that are first laid down in the new part are present in the new anterior end.

An interesting comparison may be made between the phenomenon of growth and that of contraction and expansion of the protoplasm. The bending of heliotropic organisms toward or away from the light, and the similar bending of negatively stereotropic forms away from contact with a solid body, are supposed to be phenomena of growth, and resemble in many ways the phenomenon of contraction. In a plant that bends toward the light, it is found that the most obvious change involves the amount of water on the two sides of the stem, and this is most probably connected with a fundamental structural change in the protoplasm, that is too subtile for further analysis. In the regeneration of some forms it is found that they respond in the same way to light. While it cannot be demonstrated that these phenomena really depend on processes of contraction and of expansion, the results are nevertheless suggestive from this point of view. Furthermore, I think, one cannot study the regeneration of such forms as planarians, hydras, stentors, etc., without being struck by the apparent resemblance of the change in form that they undergo to a process of expansion. The idea of the expansion of a viscid body carries with it, of course, the idea of tension within the parts, and the return to the former condition is brought about by a release from the tension and a return to a more stable condition. If by the intercalation of new material the extended condition is fixed, a new state of equilibrium will be established.

It has been already pointed out that in a piece of a plant suspended in a moist atmosphere, the apical buds are those that first develop, and also grow faster than the others. The buds situated nearer the base may not even begin to develop, although they are at first as favorably situated, so far as external circumstances are concerned, as the uppermost ones. The roots appear first over the basal end, and those nearer the base grow faster than do those nearer the apex. There cannot be much doubt that the suppression of the basal buds and of the more apical roots is connected with the development of the apical buds and of the basal roots. This can be shown by cutting a piece in two, when some of the basal buds will grow into shoots and the apically situated root-buds, that are now on the base of one piece, will begin to grow. It seems to me this relation can be at least more fully grasped, if we look upon it as connected with some condition of tension in the living part. The tension can be thought of as existing throughout the softer, more plastic parts. As long as the apical bud is present at the end of a stem or branch, or even near the apex, it exerts on the parts lying proximal to it a pull, or tension, that holds the development of these parts in check; but if the apical bud is removed the tension is relaxed, and the chance for another bud developing is given.

It may be asked, how can it be explained that only the more apically situated buds of a piece develop, rather than the basal ones, since with the removal of the piece from the plant the tension has been removed also. The only answer that can be made, so far as I can see, would be that from the apex of the plant to its base the tension is graded, being least at the apex and increasing as we pass to the base. Those buds will first develop that are in the region of least tension, and their development will hold in check the other buds by increasing or reëstablishing the tension on the lower parts of the piece. A new system is then established, like that in the normal plant.

There are certain experiments with hydra that can, perhaps, be brought under the same point of view. When two long posterior pieces are united by their anterior cut-surfaces, each piece regenerates a circle of tentacles near the region of union, and each may produce a new head; or only one head, common to both pieces, develops at the side. Each piece has retained its individuality, which may be interpreted to mean that each piece has retained its original condition of tension. If, however, after a union of this kind one piece is cut off, as soon as the two have well united, near the place of union, so that it is relatively small as compared with the other component, it may produce a head at its exposed basal end, and neither heads nor tentacles may develop at the place of union of the pieces.

It is probable, in this case, that the larger component has acted on the smaller one, so that its polarity is changed and becomes like that of the larger component. It is possible, I think, to interpret this result in terms of our tension hypothesis. The condition of tension in the larger piece has overcome that of the smaller piece, so that the latter comes to have the same orientation that the larger piece has; and the development of a head at the free end then takes place. The development of this head holds in check the development of a head at the anterior end of the larger piece in the region of union of the pieces. When two pieces of hydra are united by unlike poles, i.e. so that they have the same orientation, it is found that if the pieces are not too long, a head develops at the free end and none in the region of grafting. The result is similar to that in plants; the development of the head at the free end suppressing any tendency that may exist to produce a new head by the posterior piece at the place of union. If the pieces united in this way are very long, a head develops at the apical end, and, in some cases, also near the line of union. This may be due to the pieces being so different at the place of union, that a head develops below this region before the unification of the two pieces is brought about, or because the formation of the head at the free end is relatively so far removed from the place of union of the pieces, that it does not influence the development of a head in this region.

These cases of grafting also illustrate another point of some interest. They show that the development of a head at the anterior end of a piece is not the result of the injury from the cutting or due to the action of some external condition on the free end, for the regeneration may take place when two anterior ends have been perfectly united to each other. The result can only be explained as the outcome of some internal factor such as polarity.

These examples have been chosen from hydra rather than from tubularia, in which somewhat similar phenomena have been observed, because in hydra the development of heteromorphic structures is of rare occurrence, while in tubularia external influence often calls forth a heteromorphic development. There cannot be much doubt, however, that in tubularia the same kind of internal factors are also at work.

A more striking illustration of the possible influence of tension of the parts is shown by an experiment with planarians. If the head of a planarian is cut off and the posterior piece is split partially in two along the middle line, as shown in [Fig. 31], A, and then one of the halves is cut off just anterior to the end of the longitudinal cut, the result is as follows: A new head develops at the anterior end of the long half ([Fig. 31], B), but no head develops on the posterior cut-surface, provided this part has reunited along the middle line with the long half, and a line of new tissue connects the anterior cut-surface of the long half and the more posterior cut-surface of the shorter half. At least this happens if the piece is not split too far posteriorly, i.e. through the region of the pharynx. If this is done, a new head may develop from the posterior cut-surface. In another way the development of the more posterior head can be brought about. If the shorter side-piece is kept from fusing with the longer side-piece in the middle line, it will invariably produce a new head ([Fig. 31], C). The lack of development of the posterior head, when the two cross-cut surfaces are united by a connecting part of new material, can, it seems to me, be best explained by the influence of the developing anterior head, or of the new side on the posterior new tissue, and this influence can, I think, be better appreciated if we suppose some sort of tension to be the influence at work.