Private sorrows--Death of Pasteur, 1895--Ill-health--Senile
atrophies--Premature death--Orthobiosis--Syphilis--Acquisition
of anthropoid apes.
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.