Regeneration

by Thomas Hunt Morgan

Giants may be looked upon as hypertrophied individuals, since all the organs of the body are larger than the normal. The enlargement is, in this case, not due to external influences, but to some peculiarity of the organism itself. Whether the size is due to more cells being present, as seems probable, or to the cells being larger, or to both, has not, so far as I know, been determined for man. In a mollusk, Crepidula fornicata, in which large and small adult individuals occur, it has been shown by Conklin (’98) that the difference is due entirely to the larger number of cells in the larger individual. In this case external conditions, in so far as they retard the maximum possible growth of the individual, are responsible for the differences in size. The distinction is, in this case, rather between large normal individuals and dwarfs, than between giants and normal or average individuals.

The voluntary muscles of the body of man grow larger, and may be said to hypertrophy, as a result of doing certain kinds of work. The muscles of the hand and arm grow large through use, and become smaller again if not used; but the muscles of the fingers of a musician do not hypertrophy, although the total amount of work done may be very large. It is only when muscular work is done against great resistance that enlargement of the muscles takes place. The factors that may bring about the enlargement will be discussed later.

The kidneys seem to give the most satisfactory evidence of compensating hypertrophy. Nothnagel[52] states that it has been shown in man, in the rabbit, and in the dog, that when one kidney has been removed the other enlarges; and that this takes place both for young animals, in which the kidneys have not reached their full size, and in adult animals, in which the remaining kidney becomes larger than normal. In the adult the enlargement is due to hypertrophy, in Virchow’s sense, in the tubules and in the epithelium of the canals. In the young animal there is, in addition, a hyperplastic growth that leads to an increase in the number of glomeruli, etc.

Experiments have shown that the same amount of urea is excreted by the animal after the removal of one kidney as before; in fact, this is true immediately after the operation, before any increase in the size of the organ has taken place. This means that, under normal conditions, the kidneys do not perform their maximum of work. It is important to observe in this connection that the remaining kidney gets more blood than it would get if the other were present. Nothnagel sums up the changes that take place in this way: First, the removal of one kidney; second, an increase in the flow of blood in the remaining kidney; third, an increase in the functional activity and excretion of this kidney; fourth, along with the increase in the flow of blood, there is a necessary increase in the amount of food that is brought to the kidney in the blood; fifth, this food is taken up in larger amount than before by the cells, which leads to an increase in the growth of the cells, which produces hypertrophy. The increase in size, looked at from this point of view, Nothnagel says, has nothing mysterious about it. The enlargement seems to be an adaptation; but the enlargement does not take place because it is an adaptive process, but because it cannot be helped under the conditions that arise. We shall return again to Nothnagel’s interpretation, when we come to consider other views.

Experiments of the sort just described are most easily carried out on the paired organs of the body, such as the salivary glands, the tear glands, the mammæ of the female, and the testes of the male. In regard to the latter two organs the evidence, especially in the case of the testes, is conflicting, but the recent experiments of Ribbert seem to give definite results. Nothnagel had found that after the removal of one testis there is no hypertrophy of the other. He pointed out that this result does not stand in contradiction to his hypothesis in regard to the kidneys, for the loss of one testis does not lead to a greater functional activity in the other. Each acts for itself alone. The result shows further, he adds, that the process of hypertrophy is not an adaptive one, but a physical or a physiological process. Ribbert on the contrary thinks that even Nothnagel’s statistics give evidence of hypertrophy, and Ribbert’s own experiments give unmistakable evidence of a considerable enlargement of the remaining testis. In his experiments, young rabbits were used that were born of the same mother and in the same litter. One of the testes was removed from some of the individuals, and after some months the remaining testis was taken out and its weight compared with that of the control animal. In sixteen out of seventeen experiments there was found to be a noticeable increase in the single testis as compared with either testis of the control animal. The results show that in some cases the single testis weighs almost as much as the two together of the control animal. It is important also to notice that in this case the enlargement has taken place in an organ that has not been active, as was the case with the kidney.

Ribbert has also shown that hypertrophy takes place in the mammæ of the rabbit after the removal of some of them. Five out of the eight mammæ were removed in three cases, and seven out of the eight in two other cases from young rabbits about two months old. Ribbert found that if the operator is not careful to remove completely all the tissue of a mamma an active regenerative process takes place from the part that remains. After five and a half months the single remaining mamma of one animal measured six and one-half by three and four-fifths centimetres, and the corresponding one in the control animal five and three-fourths by three and one-half centimetres. The glandular tissue was also found less developed in the control animal.

In another experiment the rabbit experimented upon bore young when it was six and a half months old. Soon after the birth of the young and before the mamma had been used the animal was killed and the single mamma that had been left was measured. It was much enlarged and projected more than the normal mammæ. It measured nine by five centimetres. In a normal control animal[53] the corresponding mamma measured seven by five centimetres. The number of acini was in the proportion of sixteen in the animal operated upon to ten in the normal. The results show a distinct compensating hypertrophy, due to a hyperplastic increase in the number of elements of the gland.

A further example of compensating hypertrophy has been found after the removal of the spleen, when the lymphatic glands of other parts of the body become enlarged. There are also observations which go to show that after the removal of some of the lymphatic glands others undergo an enlargement.

Ziegler[54] has given a critical review of the various opinions and hypotheses that have been advanced to account for the process of hypertrophy. According to Cohnheim[55] hypertrophy in bones, muscles, spleen, and glands is due to hyperæmia, i.e. increased blood supply. He thinks that neither mechanical nor chemical stimuli can cause directly new processes of growth. Recklinghausen[56] thinks that hypertrophy is not due to any extent to an increase in the food supply. Samuel[57] explains hypertrophy as due to a removal of, or to a decrease in, the resistance to growth and also to the influence of the nerves. Klebs[58] thinks that three factors enter into the problem, (a) inherited peculiarities, (b) overfeeding, (c) a removal of the controlling influences. Weigert believes that reparative processes are due to the removal of influences that prevent growth, and not to a direct stimulus. He thinks that a stimulus may start a functional act, but can never start a nutritive or a formative one. Good nourishment, for instance, may bring a tissue to a maximum development that is predetermined by innate peculiarities, but “idioplastic forces” are not thereby increased. Pekelharing[59] thinks that hypertrophy is due to a disappearance of a resistance to growth, and also to a stimulus causing proliferation.

We see from these various opinions how little is really known; how little has been determined as yet by experiment as to the causes that bring about hypertrophy. Many of the views are more or less plausible in the absence of direct, experimental evidence, but it remains for the future to decide as to the correctness of all of them. They are valuable as suggestions, in so far as they show the different possibilities that must be taken into account.