Regeneration

by Thomas Hunt Morgan

Exception may be taken, I believe, to parts of Vöchting’s conclusions, especially in the light of the recent experiments in grafting in animals. It is by no means to be granted without further demonstration that the properties of the whole organism are only the sum-total of the action of the individual cells. If, as seems to be the case, the cells are organically united into a whole, the properties of this whole may be very different from the sum of the properties of the individual cells, just as the properties of sugar are entirely different from the sum of the properties of carbon, hydrogen, and oxygen.

The statement that like poles repel and unlike poles attract is, I believe, a conclusion that goes beyond the evidence. The experiments show that like poles do often unite in plants, and this has been abundantly shown to be the case in the lower animals, and even in forms as high as the earthworm and the tadpole. Even if when like poles are united subsequent changes take place, that in some cases, although apparently not in animals, lead to the death of the graft, it by no means follows that this has anything to do with the attraction or repulsion of the parts, but rather with some difficulty in obtaining food, or with the transportation of substances through the plant. In the lower animals we have seen that when like poles are united there is sometimes a stronger tendency to produce new organs at or near the place of union than when unlike poles are united, but it would be going too far, I think, to state that this is due to repulsion of the parts, especially in the sense in which the like poles of a magnet repel each other. It seems to be due rather to the two parts failing to unite into a whole organization, each retaining the same structural basis that it had before grafting, but this is a very different principle from that of an attraction and repulsion of the parts, and the question of the union of the parts appears also to be a different question from that of the organization of the parts themselves.

In the mammals, and in general in all forms in which there is a dependence of the parts on each other, it is impossible to carry out grafting-experiments on the same scale as those described in the preceding pages. The principal difficulties are to make the parts unite, and to supply nourishment and oxygen to the graft. Owing to the dependence of the parts of the body on each other for a constant supply of oxygen and food derived from the blood, as well as for the removal of the waste products, the parts cannot remain alive, or even in good condition, while new connections are being established. For this reason, as well as for others, it would not be possible, for instance, to graft the arm of a man upon another man. The tissue may have the power of uniting even in this case, as is seen when the bone is broken and subsequently reunited, but the difficulty would be in supplying the grafted arm with nourishment, etc., during the long time required for the union to take place. Smaller parts of the body may be successfully grafted, and there are several recorded cases in which parts of a finger, or of the nose, are said to have been cut off and to have reunited after being quickly put back in place. Pieces of human skin may be grafted without great difficulty upon an exposed surface, and it has been said that small pieces succeed better than larger ones, owing, most probably, to their being able to absorb sufficient oxygen, etc., and keep alive until new blood vessels have grown into the grafted piece.

There are a number of old and curious observations in regard to cases of grafting in higher animals. It was found by Hunter and by Duhamel that the spur of a young cock could be grafted upon the comb, when it continued to grow to its normal size. The comb, being richly supplied with blood, furnished the nourishment for the growth of the spur. Fischer transplanted the leg of an embryo bird to the comb of a cock, or of a hen, where it grew at first, but after some months degenerated. Zahn transplanted the fœtal femur to the kidney, where it grew for a time, but later degenerated. Bert transplanted the tail of a white rat to the body of Mus decumanus, where it continued alive; but he found that the tail of the field mouse, Mus sylvaticus, did not grow so well on the rat, and the tail of a rat would not unite at all with the body of a dog or of a cat. Bert bent over the tip of the tail of a rat, and grafted the distal end into the skin of the back of the same animal. After the tip had established union with the surrounding tissues, the tail was cut off at its base. The grafted tail remained alive, but did not regenerate at its free end.

There are several cases described by pathologists in which the skin of one mammal has been transplanted to another. The transplantation of the skin of the negro upon a white man has been brought about, but the evidence as to what subsequently happened is contradictory. It appears that while in many instances the transplanted skin has remained alive for a time, yet later it was thrown off by new skin growing under it and replacing it.

Leo Loeb has described a curious instance of grafting pieces of skin of different colors in the guinea pig. If a piece of black skin from the ear of a guinea pig is grafted upon the white ear of another animal, it unites and continues to live, but if a piece of white skin is grafted upon a black ear, it is slowly thrown off and replaced by new black skin that has regenerated around the edge of the graft from the tissue of the black ear.

In the literature of pathology there are many cases described in which parts of the body of mammals, particularly internal organs, have been grafted in unusual regions. The results have not always been the same, for while in some cases it appears that the operation has succeeded, in others the grafted part is subsequently absorbed, and in still other cases the graft may be at first partly absorbed and later begin to grow again. It appears that the establishment of an adequate blood supply is the most important element of success. Ribbert, who has made an extensive and successful series of experiments, has stated that the grafting takes place better when small pieces of an organ are used, since these can draw immediately on the surrounding regions for their oxygen, etc., while larger pieces are found to break down in the interior, owing to the fact that this part is too far removed from the supply of oxygen, food, etc. After the grafted piece has established a blood supply of its own, it may continue to grow. Ribbert transplanted small pieces of different tissues of the rabbit and guinea pig in, and upon the surface of, the lymph glands of the same or of another individual. The lymph gland was chosen because small pieces of tissue can be afterwards easily detected. A small piece of tissue about as large as a pin’s head is cut off from whatever tissue is to be grafted, and as quickly as possible placed in a small cleft made in the lymph gland. After several days, weeks, or months, the gland is removed and the graft examined by means of serial sections.

Most of the experiments were made with “epithelial organs,” and according to Ribbert, if pieces of such organs are composed of epithelium only, they cannot be successfully grafted. For instance, the cells of the cornea can be readily separated from their underlying connective tissue, and can be kept alive in the lymph gland, but the cells diminish in number, show retrogressive metamorphosis in the direction of atrophy, and are finally absorbed. It seems that epithelium by itself cannot extract nourishment from its surroundings. Nothing is easier, however, than to transplant epithelium, if its connective tissue is present. The connective tissue furnishes so good a basis for nourishment that the epithelium not only lives, but may continue to proliferate. Ribbert finds that pieces of skin roll in after their removal. Then a process of growth takes place corresponding to that which follows a wound in the skin. The surface is closed and a small cyst is formed with a central cavity. The epithelium undergoes no changes during the first days or weeks. It remains stratified and shows an active process of cornification and desquamation. Similar results were obtained when pieces of the conjunctiva were transplanted, either under the skin in the anterior chamber of the eye, or in the lymph gland.

A small piece of the lining epithelium of the trachea with its underlying cartilage was also placed in the lymph gland. The epithelium grew, and covered over the wounded surface, forming over it only a single layer of cells. The old many-layered epithelium also became arranged in a single layer.

The wax glands, found in the inguinal folds of the rabbit, were also transplanted. The gland is composed of closed, compressed alveoli, surrounded by large, polygonal, clear cells. Small pieces of a gland, transplanted upon the lymph gland, underwent characteristic changes. The cells of the alveoli were changed into a stratified epithelium; and broken-down cells, and wax, were found in the interior of the alveoli. The central alveoli underwent the greatest change, while some of the peripheral alveoli that were in contact with the lymph gland remained unchanged. It seems that the difference is due to the better nourishment of the outer alveoli. After several months the alveoli swell up and degenerate. Transplanted pieces of the salivary glands also change, the alveoli producing a lining epithelium like that of the transplanted wax gland. The same change was observed in a piece of a salivary gland transplanted in the body cavity.