Читать книгу The Prolongation of Life: Optimistic Studies - Élie Metchnikoff - Страница 7

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Hypothesis of the causation of senility—Senility cannot be attributed to the cessation of the power of reproduction of the cells of the body—Growth of the hair and the nails in old age—Inner mechanism of the senescence of the tissues—Notwithstanding the criticisms of M. Marinesco, the neuronophags are true phagocytes—The whitening of hair and the destruction of nerve cells, as arguments against a theory of old age based on the failure of the reproductive powers of the cells

Although it has not been proved that living matter must inevitably undergo senile decrepitude, it is none the less true that man and his nearest allies generally exhibit such degeneration. It is therefore extremely important to recognise the real causes of our senescence. There have been many hypotheses on the subject, but there are comparatively few definite facts known.

Bütschli has supposed that the life of cells is maintained by a specific vital ferment which becomes feebler in proportion to the extent of cellular reproduction, but I cannot regard this as more than a pious opinion. The ferment has never been seen, and we do not know of its actual existence. According to the better-known theory of Prof. Weismann, old age depends on a limitation in the power of cells to reproduce, so that a time comes when the body can no longer replace the wastage of cells which is an inevitable accompaniment of life. As old age appears at different times in different species and different individuals, Weismann has concluded that the possible number of cell generations differs in different cases. He has not found, however, a solution of the problem as to why multiplication of cells should cease in one individual, whereas it proceeds much further in other individuals. Prof. Minot,6 the American zoologist, has developed a similar theory, and has employed an exact method to determine the gradual diminution in the rate of growth of an animal from its birth onwards. According to him, the power of reproduction of the cells weakens progressively during life, until a point is necessarily reached at which the organism, no longer capable of repairing itself, begins to atrophy and degenerate. Dr. Buehler7 has recently laid stress upon this theory.

There is no doubt that cells reproduce much more actively during the embryonic period. The process becomes slower later on, but, none the less, continues to display itself throughout the whole period of life. Buehler attributes the difficulty with which certain wounds heal in the case of old people to the insufficiency of cellular reproduction. He thinks in particular that the proliferation of the cells of the skin, to replace those which are worn off from the surface, becomes less active with age. According to him, it is theoretically obvious that a time must come when the replacement of the epidermic cells completely ceases. As the superficial layers of the skin continue to dry up and be cast off, it is plain that the epidermis must disappear completely. Buehler thinks that there must be a similar fate for the genital glands, the muscles, and all the other organs.

These theoretical considerations, however, are not compatible with certain well-known facts indicating that there is no general cessation of the power of cell reproduction in old age. The hairs and the nails, which are epidermic outgrowths, continue to grow throughout life, their growth being due to the proliferation of their constituent cells. There is no sign of any arrest in the development of these structures, even in the most advanced old age. The reverse is true. It is well known that the hairs on some parts of the body increase in number and in length in old people. In some lower races, for instance in the Mongols, the moustache and the beard grow vigorously in old age, whilst young people of the same race have only very small moustaches and practically no trace of beard. So also in white women the fine and almost invisible down which covers the upper lip, the chin, and the cheeks in the young may become replaced by long hairs which form a moustache or beard.

Dr. Pohl, a specialist in the growth of hair, has measured the rate of growth in different circumstances. He has shown that in an old man of 61 the hair on the temple grew 11 mm. in a month; on the other hand, the hair on the same region in boys of 11 to 15 years old grew in the same time only from 11 to 12 mm. Plainly, there is no case here of a progressive diminution of cell-proliferation with age. The same observer, it is true, has shown that the hair of young men of between 21 and 24 years grew at the rate of 15 mm. a month, whilst in the same individuals, at the age of 61 years, the rate of growth was only 11 mm.; but this diminution in the rate of growth is only apparent. The first figure concerned the hair taken from different regions of the scalp, whilst the second related only to the hair on the temples, and Dr. Pohl himself has shown that, in the latter region, the hair grows slower than in other regions. Moreover, in many boys of 11 to 15 years old, studied by this observer, the rate of growth was always less than 15 mm., and often less even than the 11 mm. recorded in the old man of 61.

I have been able to note that the nails grow even in very old people. In the case of Mme. Robineau, the centenarian, the nail of the middle finger of the left hand grew 2–½ mm. in three weeks. In the case of a lady of 32 years old, the corresponding nail grew 3 mm. in two weeks, the difference being out of all proportion to the enormous difference in the age. The centenarian’s nails had to be cut from time to time.

Although the hairs of old people grow, they become white, which is a phenomenon of senile degeneration. Although they increase in length, the colouring matter in them becomes reduced and finally disappears. In the “Nature of Man” I described the process by which this blanching takes place, and which may now be regarded as definitely proved. It is useful as a means of interpreting the real nature of the process of senescence. In several published works, I have explained my belief that just as the pigment of the hair is destroyed by phagocytes, so also the atrophy of other organs of the body, in old age, is very frequently due to the action of devouring cells which I have called macrophags. These are the phagocytes that destroy the higher elements of the body, such as the nervous and muscular cells, and the cells of the liver and kidneys. This part of my theory has encountered very strong criticism, especially with regard to the part played by the macrophags in the senescence of nervous tissue.

Neurologists in particular, have criticised my interpretation. For several years M. Marinesco8 has attacked my theory of the atrophy of the nerve-cells in old age. In the first place, he has stated that in old people, and even if these are very old, it is rare to find phagocytes surrounding and devouring the cells of the brain. In support of this contention, he has been good enough to send me two preparations made from the brains of two very old persons. After careful examination I was convinced that my opponent had been inexact. In the brain of the two centenarians (one of whom died at the age of 117 years) there were very many nerve-cells surrounded by phagocytes and in process of being destroyed by them. It happened, however, that as the sections were very weakly stained, it was more difficult to observe the facts than in the preparations upon which I had made my own observations. I have already recorded this fact in the second and third French editions of the “Nature of Man.”

Without taking notice of my reply, M. Marinesco has published another criticism of my theory in an article9 entitled “Histological Investigations into the Mechanism of Senility.” In that work, although he himself had invented the designation “neuronophag” for a phagocyte that devours nerve-cells, he denies the existence of such a power. He thinks that nerve-cells atrophy independently of the cells that surround them. The latter, the so-called neuronophags, only contribute to the atrophy inasmuch as they press against the nerve-cells and deprive them of nutrition. He is confident that the constituent parts of nerve-cells are never found in the neuronophags. There is no question of phagocytosis, of the existence of cells that devour their neighbours.

M. Léri has taken a similar view in a Report on the Senile Brain10 presented to a recent congress of alienists and neurologists. According to him “the nuclei which surround some of the atrophying nerve-cells do not play the part of neuronophags.” In his monograph “La Neuronophagie,”11 M. Sand elaborates the same view. He relies on his observation that “neuronophags are usually either devoid of protoplasm or display only a very thin layer of it. They never exhibit protoplasmic outgrowths, and they never have granules in their cellular bodies (p. 86).” Still more recently MM. Laignel-Lavastine and Voisin12 have taken the same view, maintaining that the neuronophags do not display phagocytosis.

Although I cannot undertake here to give a detailed reply to the arguments of my critics, I may point out a fallacy that vitiates their reasoning. The study of the intimate structure of nervous tissue involves the treatment of that very delicate substance by numerous active reagents. It is extremely important not to forget the possibility of alterations which may be produced in the processes of preparation and which are extremely difficult to avoid. A glance at the figures given by my critics shows me that the neuronophags in their preparations had been subjected to violent treatment. When M. Léri speaks of “the nuclei which surround some of the nerve-cells,” and M. Sand of “cells without protoplasm,” it is clear that they had been observing cells destroyed by the processes of the laboratory. The illustrations in the memoir of M. Marinesco show that in his preparations, too, the neuronophags had been very greatly altered.

It is well known that nuclei do not exist free in tissues, and that when they appear devoid of protoplasm, there has been some defect in the technical methods of preparing them for examination. As a matter of fact, neuronophags do not consist of nuclei with at the most a pellicle of protoplasm; like other cells, they have protoplasmic bodies which, however, are frequently destroyed by the violent processes of histological preparation.

The arguments of my critics recall to me the words of a medical student, who, on being asked to describe the microbe of tuberculosis, said that it was a little red bacillus. The bacillus in question, like most bacilli, is colourless, but it is usual to stain it so that it may be visible under the microscope. The student, knowing it only in particular preparations, had a false idea of its appearance.

In well-made preparations, neuronophags are typical cells with abundant protoplasm. When they have been preserved by a process that does not dissolve their contents, they show granules like those found in nerve-cells.

To study neuronophagy, M. Manouélian,13 in the laboratory of the Pasteur Institute in Paris, set himself to improve the technical methods of preparation. He succeeded in showing first that in the destruction of nerve-cells that occurs in cases of hydrophobia, the contents of these cells are absorbed by the surrounding neuronophags. “My observations on the cerebro-spinal ganglia of human cases of hydrophobia,” he wrote, “show clearly that the macrophags act as phagocytes of the nerve-cells.” “Most of the cells in the nerve-ganglia contain yellow, brown, and black pigmented granules, usually united in small masses. What becomes of these granulations on the destruction and disappearance of the nerve-cell? If, as M. Marinesco has it, there is no phagocytosis by the surrounding cells, but merely a mechanical interference, then the granules, on the destruction of the nerve-cells that contained them, should be found lying in the interstitial tissue. But this does not happen. The granules are ingested by cells which are true macrophags.”

By the aid of a very delicate mode of preparation, M. Manouélian has shown that in the case of senile brains the granules of the nerve-cells are absorbed by neuronophags. I have myself studied M. Manouélian’s preparations and can testify to the accuracy of his observations (Figs. 6 and 7).

Doubt is no longer possible. In senile degeneration the nerve-cells are surrounded by neuronophags which absorb their contents and bring about more or less complete atrophy. It has been supposed that in order to devour their contents, the neuronophags must penetrate the nerve-cells, and such an event has rarely been seen. But it is well known, the phagocytosis of red blood corpuscles being a typical instance, that to absorb a cell a phagocyte does not necessarily engulf it bodily or penetrate it, but may gradually denude it of its contents merely by resting in contact with it.

There has been some discussion as to the condition of nerve-cells which are on the point of being devoured by neuronophags. It has been noticed that such cells may display a considerable amount of degeneration without being devoured, whilst, on the other hand, cells apparently normal have been found undergoing phagocytosis. As I cannot state definitely what are the conditions that induce the phagocytosis of nerve-cells, I shall not attempt a discussion of the problem.

Although the destruction of nerve-cells by neuronophags is a general occurrence in senile brains, one may conceive of cases where this does not occur. And so, in old people who have preserved their faculties, it may well be that the neuronophags have refrained from attacking the nerve-cells. But as such instances are rare, so also phagocytosis is usually found in senile brains, and I cannot accept M. Sand’s denial of its existence, based on his study of two cases.

Fig. 6.	Fig. 7.
FIGS. 6. & 7.—Two nerve-cells from the cortex of the brain of an old dog aged fifteen years. The neuronophags surrounding the nerve-cells contain numerous granulations. (From preparations made by M. Manouélian.)

The general result of my investigation into the criticisms that have been published on this matter has confirmed me in my belief that neuronophagy plays a most important part in senescence, and recent observations that I have made with M. Weinberg have completely supported this view.

The bleaching of hair and the atrophy of the brain in old age thus furnish important arguments against the view that senescence is the result of arrest of the reproductive powers of cells. Hairs grow old and become white without ceasing to grow. The cessation of the power of reproduction cannot be the cause of the senescence of brain-cells, for these cells do not reproduce even in youth.