Cholera--Experiments on himself and others--Illness of M. Jupille
--Death of an epileptic subject--Insufficient results.
The acute period of the struggle in defence of the phagocyte theory
now seemed to have come to an end and Metchnikoff turned his thoughts
towards a new field of ideas.
Having elucidated the essence of inflammation, he wished to study the
origin of another pathological symptom, _i.e._ the rise in temperature
which constitutes a feverish condition. To that end he undertook a
succession of experiments on cold-blooded animals; he injected microbes
into crocodiles and serpents, hoping thus to provoke a rise in their
temperature. But those experiments did not give the results expected.
In the meanwhile (1892) cholera had made its appearance in France; the
specificity of the cholera vibrio was not finally established at that
time. The observations made by Pettenkoffer on the immunity of certain
regions, despite the presence of the cholera vibrio in the water, and
the experiments made upon himself by that scientist, seemed to plead
against the specificity of the cholera vibrio; but other facts spoke in
its favour. Desirous of solving this question, Metchnikoff went to a
cholera centre in Brittany in order to fetch the necessary materials.
Having done so, he attempted to produce cholera in divers kinds of
animals, but without success.
As he failed to solve the problem of the specificity of the cholera
vibrio on animals, he resolved to experiment upon himself and consumed
a culture of cholera vibriones. He did not contract cholera, which made
him doubt the specificity of the vibrio, and therefore he consented to
repeat the experiment on one of his workers (M. Latapie) who offered
to submit to it: the result was the same. He then did not hesitate to
accept the offer of a second volunteer (M. Jupille). The preceding
results having led him to suppose that the cholera vibrio became
attenuated _in vitro_ and might perhaps serve as a vaccine against
cholera, he gave a culture of long standing to the young volunteer.
To his astonishment and despair, Jupille began to manifest the typical
symptoms of cholera, and a doctor who was particularly conversant
with the clinical chart of the disease declared the case a severe one
because of the nervous symptoms which accompanied it.
Metchnikoff was in mortal anxiety, and even said to himself that he
could not survive a fatal issue. Fortunately the patient recovered,
and this terrifying experiment proved indisputably the specificity of
the cholera vibrio. Yet the irregularity of its action showed that in
certain cases conditions existed which prevented the inception of the
disease, and Metchnikoff supposed that this might be due to the action
of the different intestinal micro-organisms.
In order to simplify the question, he began by making experiments
outside the organism. He sowed the cholera vibrio with divers other
microbes and saw that some of them facilitated its culture whilst
others prevented it. Similar experiments within the organism of animals
gave no conclusive results; the simultaneous ingestion of the cholera
vibrio and of favourable microbes did not induce cholera.
The flora of the intestines, complex as it is, probably played a part
on which it was difficult to throw any light. Yet Metchnikoff did not
give up the idea of producing a vaccine against this disease with
attenuated microbes, or, if not, to prevent its inception by preventive
microbes. His thesis was strengthened when one of his pupils, Dr.
Sanarelli, discovered a series of choleriform bacilli in the absence of
any cholera epidemic, one of those microbes being found at Versailles,
a town which had remained immune during every cholera epidemic.
Metchnikoff thought that this microbe, or some choleriform bacillus,
similar though not specific, probably served as a natural vaccine
against cholera in those localities which were spared by the epidemic
though the cholera vibrio was brought there. This was a question that
could only be solved by experiment.
At the time when he had himself absorbed a cholera culture, Metchnikoff
admitted the risk of catching the disease; still, his eagerness to
solve the problem had silenced in him all other considerations and
feelings opposed to his irresistible desire to attempt the experiment.
This "psychosis," as he himself called it later, recurred now, in spite
of all the emotions he had gone through on the previous occasion, and
he decided once again to experiment on man. It is true that he now
only had to deal with choleriform microbes from Versailles which he
believed to be quite harmless as they came from the water of a locality
free from cholera. He therefore ingested some of the Versailles
choleriform vibriones and gave some to several other people. Contrary
to expectation, one of the latter, an incurable epileptic, showed some
symptoms of cholera, but recovered. But as, a short time later, this
patient died from a cause which remained obscure, Metchnikoff thought
that possibly the experiment might have had something to do with it,
and finally resolved to perform no other experiments on human beings.
How could that unforeseen result be explained? Metchnikoff supposed
that the intestine of the subject contained favourable microbes
which had exalted the virulence of the bacillus, in itself weak
and innocuous. If it were so, then certain intestinal microbes
would influence the inception of diseases and the action of the
micro-organisms would vary according to the society in which they found
themselves. As such problems could only be solved through experiment,
he again energetically sought for a means of conferring cholera upon
animals. After many failures and difficulties, it occurred to him to
try new-born animals whose intestinal flora, not yet developed, could
not interfere with the swarming of the ingested bacilli. He chose young
suckling rabbits for his experiments and, with the aid of _favourable_
microbes, he succeeded at last in giving them characteristic cholera,
through ingestion; thus it became possible to study intestinal cholera
on these animals.
However, numerous researches on the prevention of cholera by means
of divers microbes gave no results sufficiently conclusive to permit
their application to human beings. The problem was rendered extremely
complicated and difficult by the many and varied influences of numerous
intestinal microbes and the inconstancy of microbian species in the
same individual.