PROTECTIVE INOCULATION FOR CHOLERA. 225 



ences in which he described some experiments he had made with 

 the specific organism of cholera, the comma bacillus, Koch's com- 

 ma 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 propa- 

 gation of a micro-organism is called " a culture " of that organ- 

 ism. 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 fol- 

 lowed that might slough though the ulceration would heal spon- 

 taneously 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 un- 

 protected 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 dis- 

 charges 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 at- 

 tack 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 pro- 

 found immunity. 



He continued his experiments, and in 1886 sent another mem- 

 oir 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 liv- 

 ing spirillum. He furthermore stated that an active principle 

 was generated by the spirillum, that could be isolated by certain 



VOL. XLII. — 15 



