ences in which he described some experiments he had made with the specific organism of cholera, the comma bacillus, Koch's comma bacillus, the cholera spirillum, or the cholera vibrio, as it has been variously termed.
By experiment it had been learned that the cholera spirillum, like many other micro-organisms, would develop plentifully in certain nutritive substances, such as a very rich beef broth or jelly if kept at a certain temperature. Such an artificial propagation of a micro-organism is called "a culture" of that organism. Ferran found that the maximum virulence of the cholera spirillum was obtained in a culture of rich, slightly alkaline bouillon, and that from thirty to sixty drops of this culture would kill a guinea-pig, if inoculated under the animal's skin; but, if a smaller dose was inoculated, a local inflammation followed that might slough though the ulceration would heal spontaneously without forming pus; and this animal would not be subsequently affected by the injection of a quantity of the culture of the cholera spirillum that would rapidly prove fatal in an unprotected animal.
Ferran reasoned that if such a result could be obtained in the organism of a lower animal, why could it not be secured in the highest animal? Accordingly, he injected hypodermically in man, fifteen drops of his virulent culture: a hot, painful tumor, with local fever, and malaise followed, but without choleraic discharges from the bowels; and these symptoms disappeared in twenty-four hours. If a similar quantity was reinjected in the man a week later no general and few local symptoms followed. He therefore considered that by these injections of graduated doses he could arouse in each person's system that resistance to the disease that has been heretofore referred to. He did not believe that the cholera spirillum multiplied in the cellular tissue that is beneath the skin, but that it produced in the tumor formed at the point of inoculation a rapidly diffusible toxine that exercised some influence upon the nervous centers. The dangers of an attack of, and death from, cholera begin to disappear five days after the first inoculation, and each successive inoculation increases the guarantee of immunity; three inoculations, each of thirty drops of the bouillon culture, at intervals of five days, produced a profound immunity.
He continued his experiments, and in 1886 sent another memoir to the French Academy of Sciences, wherein he stated that cultures of the comma spirillum in which the living organism had been destroyed by a high temperature, would, when inoculated confer a tolerance that successfully resisted the effects of the living spirillum. He furthermore stated that an active principle was generated by the spirillum, that could be isolated by certain
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