Metchnikoff’s health had suffered from the numerous emotions provoked by the struggle in defence of the phagocyte doctrine and also from a series of sad events. In 1893, sickness and death fell upon our family; I lost a sister and a brother at a short interval and had myself to undergo a serious operation. My husband nursed me night and day, as a mother might have done, and went through the deepest anxiety on account of post-operative complications. All this told on him all the more that he had just endured cruel moral suffering during the experiments on cholera mentioned above. In 1894, an agricultural crisis in Russia influenced our material situation and gave him many worries. In the autumn of 1895, M. Pasteur’s health became worse and, soon afterwards, he died.

This series of calamities depressed Metchnikoff, his old cardiac trouble returned, and he again became a prey to insomnia. We spent part of the holidays in the mountains, thinking it might do him good, but he did not care for a prolonged rest; he was preoccupied by the thought of his interrupted experiments and only thought of returning to the laboratory.

In 1898, he had some disquieting symptoms of kidney trouble, a little albumen. He consulted the celebrated German physician, von Noorden, who found nothing serious, but this did not reassure him and he continued to worry about himself.

Already some time previously, theoretical considerations on senile atrophies had directed his thoughts towards old age. His reflections now turned towards the psychological aspect of the problem; he analysed his personal sensations and realised that he, at the age of 53, felt an ardent desire to live. This imperious instinct for life, in spite of the inevitable evolution towards personal death and old age, brought his thoughts back to the disharmonies of human nature. But now, through all his gloomy reflections, he was borne up by the unshakable conviction that Science would succeed in correcting those disharmonies and he continued to work with untiring energy.

He had prescribed for himself a hygienic diet, based on the idea that the cause of his own condition and senility in general was due to a chronic poisoning by intestinal microbes. This diet consisted in avoiding raw food in order not to introduce noxious microbes into the intestines, and in absorbing their useful enemies, the acid-forming microbes of sour milk. This diet was very favourable to his health.

After he had finished his book on immunity he at last allowed himself to pass on to the new questions which preoccupied him, i.e. senility and death.

He set forth a sketch of his ideas in 1901 in a paper which he read at Manchester (Wilde Lecture) on the “Flora of the Human Body.” He reviewed this flora and pointed out the harmful effect of the microbes, especially those of the large intestine the toxins of which effect a chronic poisoning of the cells of our organism and thus provoke their gradual weakening. He then indicated the means of combating this evil, on the one hand by stimulating the vital activity of the cells exposed to enfeeblement, by means, for instance, of small doses of specific cytotoxins, and, on the other hand, by direct action on intestinal microbes. He concluded by saying that “the intestinal flora is the principal cause of the too short duration of our life, which flickers out before having reached its goal. Human conscience has succeeded in making this injustice obvious; Science must now set to work to correct it. It will succeed in doing so, and it is to be hoped that the opening century will witness the solution of this great problem.”

Metchnikoff considered that our chronic poisoning by intestinal microbes weakens our cellular elements; he supposed that the same cause might provoke senile phenomena, manifestly due to weakness of the tissues.

One of the first manifestations of senility being the whitening of hair, he began to study the mechanism of that. He had previously observed the dominant part played by phagocytosis in all phenomena of atrophy, and it occurred to him that it may be phagocytes which destroy the colouring matter of hair, a substance which, in the form of tiny granules, is enclosed within the hair cells. In fact, he found that the whitening process is accompanied by a stimulation of the amoeboid cells which introduce their protoplasmic prolongations into the periphery of the hair. They absorb the coloured granules, or pigment, and digest it, partly on the spot, partly after carrying it into the root of the hair, often even in the connective tissue which supports the hairy scalp. As the pigment becomes destroyed, the hair loses its colour and whitens. The cells which devour the pigment—pigmentophages—belong to the category of macrophages which, in general, absorb all the enfeebled cells in the organism.

Metchnikoff was able to note similar phenomena in divers other senile atrophies either by his own ulterior researches or by collaboration with his pupils (MM. Salimbeni and Weinberg).

In the same way that the whitening of the hair depends on the destruction of pigment by pigmentophages, the wrinkles of the skin, weakness of the muscles, friability of the bones, and senile degenerescence of divers organs are caused by the destruction of weakened cells which do not defend themselves and thus become the prey of the stronger and more resisting macrophages. Senility is thus no other than a generalised atrophy. What is it that provokes it? The answer is: The swarming microbes in our large intestine. They form the permanent source of a slow poisoning of our organism. This fact alone suffices to explain one of the principal causes of the enfeebling of our tissues. It is not simultaneous in all the cells because of their different powers of resistance. The struggle and destruction of the weak by the strong is the cruel law of nature; therefore the macrophages, more resisting to poisons, take advantage of the weakening of other cells in order to devour them, and this is one of the causes of senility.

These reflections and the biological researches which confirmed them allowed Metchnikoff gradually to build up a philosophical doctrine, which he expounded in 1903 in his work, Études sur la nature humaine.

He considered “old age” as a pathological phenomenon. He saw in it one of the most important disharmonies of human nature, because of the fact that neither senility nor death is accompanied by a natural instinct. The accomplishment of every physiological function leads to satiety or to a desire for rest; after a busy day, man feels an instinctive need for rest and sleep. But, in his maturity, he has no desire to grow old, and in his old age none to die. It is rare that one should aspire to die, and nobody wishes to grow old. These facts are in contradiction with other natural phenomena; they are all the more discordant that they play an immense part in our psychical life.

After a general review of opinions on human nature, Metchnikoff analysed it from the biological point of view; he revealed its discords and concluded that it is far from being perfect. In his eyes, the lack of harmony in the human being is an inheritance from our animal ancestors; they have handed down to us a whole series of remains of organs which are not only useless but even harmful in the new conditions of human existence.

The large intestine, inherited from mammalian ancestors, holds the first place among those noxious organs. This reservoir of food refuse was very useful to our animal forebears in their struggle for existence; it allowed them not to interrupt their flight whilst pursued by their enemies. In man, whose life conditions are different, a large intestine of that size, without offering the same advantages, is a source of slow and continuous poisoning and a cause of premature senility and death.

Man, after acquiring a still higher development, realised these evils and made concentrated efforts to fight them and to soothe his own terrors. It is for that object that the divers religious and philosophical systems were created, in which humanity sought for consolation. Finding none there, man turned to Science, which, at first, neither solved his doubts nor eliminated his sufferings. But Science provided him with rational methods of research, owing to which he gradually progressed and conquered a series of truths, allowing him gradually to struggle against some of his troubles and to solve some of his problems. Science has already done much to diminish the diseases which are among the chief scourges of humanity. It has thrown light upon the causes of many of them and has found preventive and curative remedies for several.

Surgery, antiseptics, serotherapy, vaccinations already yield secure results. Hygiene and prophylaxis are in course of development, and a vast prospect is open to them in the future. But our heaviest burdens, senility and death, common to all, have yet scarcely been studied. Having expounded his views on senility and proved that it is a pathological phenomenon, Metchnikoff concluded that to struggle against it was quite as possible as to struggle against disease.

The principal causes which bring about premature senility are: alcoholism, chronic poisoning by intestinal microbes, and infectious diseases, headed by syphilis. Surely Science will discover efficacious means against all these.

The strengthening of the beneficent cells in our organism; the transformation of the wild intestinal flora into a cultivated flora, by the introduction of useful microbes; the struggle against infectious diseases and alcoholism—all these are workable means of fighting pathological and premature senility.

When old age becomes physiological and no longer painful it will become proportionate with the other epochs of our lives and cease to alarm us. But how is the fear of death to be explained, since it is a general and inevitable phenomenon? How is it that we have no natural instinct for death? Metchnikoff supposes that this lack of harmony in our nature comes from the fact that death is as premature as senility and arrives before the natural instinct for it has had time to develop. This supposition is confirmed by the fact that old people who have reached an exceptionally advanced age are often satiated with life and feel the need of death as we feel a need of sleep after a long day’s work. That is why we have a right to suppose that, when the limit of life has been extended, owing to scientific progress, the instinct of death will have time to develop normally and will take the place of the fear which death provokes at the present day. Both death and old age will become physiological and the greatest discord in our nature will be conquered.

Our manner of life will have to be modified and directed according to rational and scientific data if we are to run through the normal cycle of life—orthobiosis. The pursuit of that goal will even influence the basis of morals. Orthobiosis cannot be accessible to all until knowledge, rectitude, and solidarity increase among men, and until social conditions are kinder.

Man will then no longer be content with his natural inheritance; he will have to intervene actively in order to correct his disharmonies. “Even as he has modified the nature of plants and animals Man will have to modify his own nature in order to make it more harmonious.”

In order to obtain a new race, one forms an ideal in relation to the organism to be modified. “In order to modify human nature, it is necessary to realise what is the ideal in view, after which every resource of which Science disposes must be taxed in order to obtain that result. If an ideal is possible, capable of uniting men in a sort of religion of the future, it can only be based on scientific principles. And if it is true, as is so often affirmed, that it is impossible to live without faith, that faith must be faith in the power of Science.”

In those words, Metchnikoff ends his book on Human Nature.

The public at large and many critics did not understand the deep and general meaning of Metchnikoff’s thoughts. They reproached him with having an insufficiently exalted ideal, for they only saw in his doctrine the desire of postponing senility and living longer. They did not understand that to revolt against the lack of harmony in nature, through which all humanity has to suffer, not only physically but morally, was to aspire to perfection. They did not consider that, in order to attain that end, all human culture and the whole social state would have to be modified; that this could only be done through many virtues, intense energy, and great self-control. They had not understood the elevation and power of an ideal which aspired to perfect not only the direction of life but human nature itself. They had not understood the audacious beauty of such a struggle, the benefit conferred by the belief that the human will and the human mind are capable of transforming Evil into Good according to a conceived ideal!...

In the meanwhile Metchnikoff, convinced that Knowledge is Power and that “Science alone can lead suffering Humanity into the right path,” quietly continued his task.

One of the most characteristic symptoms of old age is the hardening of the arteries—arterio-sclerosis. He therefore especially wished to elucidate the mechanism of that phenomenon.

Whilst many, yet unknown, factors come into play in senility, one disease, syphilis, often provokes arterio-sclerosis, indisputably due to a morbid agent. Metchnikoff therefore began to study this disease, of which the origin is infectious—especially as he thought he could do so experimentally.

Long before this, he had conceived the idea that the study of those human diseases which cannot be transmitted to ordinary laboratory animals might be carried out on anthropoid apes, of all animals the nearest to man. He had spoken of it to M. Pasteur, but, at that time, the Institute could not afford to acquire these costly animals. In 1903, at the Madrid Congress, Metchnikoff received a 5000 fr. prize and utilised this money in the acquisition of two anthropoid apes. The same year M. Roux won the Osiris prize of 100,000 fr. which he devoted to the same object, and it was decided that the two together would undertake researches on syphilis. Other donations, 30,000 fr. from the Morosoffs of Moscow and 250 roubles from the Society of Dermatology and Syphilography of the same city, completed the capital required to execute the projected plan.

The following is a short sketch of the researches that were undertaken and the results that were obtained.

The inoculation of anthropoid apes with syphilis was successful. The chimpanzee was found to be most sensitive to the disease; it manifests primary and secondary symptoms identical with those of man. Lower monkeys, though less sensitive, also contract syphilis but generally only show primary characteristic manifestations. The possibility of rapidly provoking in apes, even of the inferior kinds, syphilitic lesions similar to those of man has a very great importance, for it provides a sure means of diagnosis in doubtful human cases. Owing to the liability of apes to contract syphilis, experimental vaccination and serotherapy could be attempted on them; but, though these experiments were sometimes encouraging, the results obtained were not constant enough to justify their application to man. Thus, it was found possible to attenuate the virus by successive passages in certain lower apes, and yet, though attenuated for the chimpanzee, it did not confer upon him immunity against the active virus.

In 1905, Schaudinn discovered the syphilitic treponema in man. By using this discoverer’s method, the same microbe was found in apes inoculated with human virus, which confirmed the specific character of the treponema.

An observation was then made which was of great importance on account of its consequences: it was ascertained that the syphilitic microbe was absorbed by the less mobile mononuclear phagocytes and remained localised near the entrance point long enough to allow of a local treatment which might succeed in being curative as it had time to act before the microbes had passed into the general circulation of the organism. This supposition was proved to be correct by a series of experiments on monkeys, and, in 1906, a young doctor, M. Maisonneuve, inoculated himself with syphilis and applied the treatment with a perfectly satisfactory result.

It might have been thought that this simple, safe, and innocuous method would at once come into practice, but it was not so. Between opposition on the one hand, and carelessness of the subjects themselves on the other, this useful discovery remained for a long time without being utilised. All the above results were obtained through experiments on anthropoid apes, and the study of syphilis, until then purely clinical, entered at last into the field of experimental science.

Researches upon syphilis were but an interlude; Metchnikoff, returning to his principal work, resumed the study of senility and of the intestinal flora. During many years he applied himself to researches concerning the part played by the latter within the organism.

He was able to confirm the deductions expounded in his Études sur la nature humaine, and in 1907 he published a new work, Essais optimistes, in which he developed the same ideas, amplified by the results of his new researches, and answering the criticisms excited by his first book.

In the Essais optimistes he studied first of all the phenomena of old age in the different grades of the scale of living beings, of which he compared the life duration. He concluded that there was an indubitable connection between this and the intestinal flora.

The shorter the intestine, the fewer microbes it contains and the longer the relative duration of life. As an example, he quoted the relatively great longevity of birds and bats. Those animals, adapted to aerial life, have to weigh as little as possible. To that end, they empty their intestine very frequently and this in consequence is not used as a reservoir for alimentary refuse; as it is but little developed, it contains a much smaller number of microbes. The longevity of flying animals is relatively much greater than that of mammals with a large intestine full of microbes, a constant source of slow poisoning.

After treating the question of longevity, Metchnikoff dealt with that of death.

Living beings die, in the great majority of cases, in consequence of diseases or accidents with an external cause; one involuntarily wonders whether there is such a thing as “natural death,” i.e. arising exclusively from causes due to the organism itself. A review of known facts allowed Metchnikoff to draw the following conclusions: unicellular inferior beings have no natural death; they merely die by accident. Their individual life is very short and comes to an end by multiplication or division of a unit into two; there is no trace of a corpse in this loss of previous individuality.

Among superior plants, certain trees attain considerable dimensions (dragon-tree, baobab, oak, cypress), live for centuries, and die from external causes. Their organism presents no internal necessity for a natural death. On the other hand, a multitude of other plants have but a short life and their natural death coincides usually with the ripening of the seed. It has even been observed that it is possible to retard the death of a plant by preventing it from fructifying. For instance, lawns made up of grass mown before it runs to seed remain green and living whilst grass allowed to flower and bear seed becomes yellow and dries up. It is a well-known fact that fruits and seeds are frequently poisonous. Therefore Metchnikoff supposed that the death of the plant may be due to an auto-intoxication by poisons manufactured by it in order to defend its seeds and ensure the next generation; in Nature, the individual does not count, but the species. Once the survival of this is ensured the individual may disappear.

A similar phenomenon of auto-intoxication is manifested by lower vegetables, yeasts, and microbes. Pasteur, who discovered the microbe of lactic fermentation, found that this micro-organism, which itself produces lactic acid, perishes because of the over-production of this substance. Yeasts, again, cannot bear an excess of alcohol, their own product. Thus the vegetable kingdom offers us examples of the absence of natural death as well as examples of a natural death due to an auto-intoxication of the organism.

In the animal kingdom examples of natural death are also to be found, but only very exceptionally. Those examples are provided by Rotifera (inferior worms) and by EphemeridÆ. Their adult life is reduced to the sexual act, almost immediately followed by death without an external cause. Their life is so short that they do not even feed and lack developed buccal organs. That in itself constitutes an organic cause of inevitable, i.e. natural, death.

Among human beings natural death is extremely rare. It sometimes occurs in very old people, under the shape of a peaceful last sleep. The likeness it bears to sleep is so striking that Metchnikoff thought himself authorised to form the following hypothesis concerning the analogy in their mechanism.

According to a theory of Preyer’s, fatigue and sleep are due to a periodical auto-intoxication set up by the products of the vital activity of our organism. These products are destroyed by oxidation during sleep, after which fatigue disappears and awakening comes. According to Metchnikoff it may be that the mechanism of natural death also consists in an auto-intoxication by the progressive accumulation of toxic products during the whole of life. The analogy between sleep and natural death allows the supposition that, as before going to sleep an instinctive desire for rest is felt, in the same way natural death must be preceded by an instinctive desire to die. Moreover, this is confirmed by concrete examples. Thus that of an old woman of ninety-three who expressed that desire in the following terms to her great-nephew: “If ever you reach my age, you will see that death becomes desired just like sleep.” The same thought had been expressed by the biblical patriarchs who fell asleep satiated with life.

When, owing to the progress of Science, men reach the development of the instinct of death, they will look upon Death with the same calm as do very old people, and it will cease to be one of the principal causes of pessimism. It is for that reason that we must learn to prolong life and to allow all men to realise their complete and natural vital cycle, thus ensuring their moral balance.

Psychological observations allowed Metchnikoff to conclude that pessimism is much more frequent in youth than in maturity or in old age. He attributes this to the gradual development of the vital instinct which is only completely manifested in middle age. Man then begins to appreciate life; made wiser by experience, he demands less and is therefore better balanced.

Metchnikoff proffers examples in support of his theory. He analyses the psychic evolution of Goethe as reflected in his Faust and describes that of “an intimate friend.” These examples prove that natural psychological evolution already leads to a relative optimism. But, as long as senility is pathological and death premature, the apprehension that they inspire antagonises the normal evolution of optimism. A victory over those present evils will direct the normal course of life in the right way; one normal active period will succeed another; the accomplishment of individual and social functions corresponding with each period will become realisable; the death instinct will have time to develop, and Man, having been through his normal vital cycle, will sink, peacefully and without fear, into eternal sleep.