IMMUNITY AGAINST CHOLERA. 42 1 



being within certain limits specific, constitute an additional aid 

 in the diagnosis of an organism supposed to be the cholera 

 spirillum. 



A curious fact, however, is, that immunity produced by the above method 

 is only exerted against the living organisms, and does not protect against the 

 toxins — that is, it is due to certain substances which act as germicides (indi- 

 rectly), but which are not antitoxic. Further, it does not protect the guinea- 

 pig from the intestinal infection by Koch's method (Pfeiifer and Wassermann, 

 Sobernheim, Klein), nor does the anti-cholera serum protect young rabbits 

 against the choleraic affection produced by ingestion of the cholera vibrios 

 (Metchnikoff). The inference from these latter results appears to be, that 

 when the vibrios are introduced into the tissues, they are killed by certain 

 substances in the serum, but in the intestine they are in a sense outside of the 

 tissues, and can there multiply and produce toxins. Metchnikoff has prepared 

 a true antitoxic cholera serum by injections of repeated and gradually increased 

 doses of the toxin, and has found that this antitoxic serum has a distinct effect 

 against the choleraic affection of rabbits. 



Anti-cholera Inoculation. — Haffkine's method for inoculation 

 against cholera exemplifies the above principles. It depends 

 upon (a) attenuation of the virus — that is, the cholera organism, 

 and (b) exaltation of the virus. The virulence of the organism 

 is diminished by passing a current of sterile air over the surface 

 of the cultures, or by various other methods. The virulence is 

 exalted by the method oi passage — that is, by growing the organ- 

 ism in the peritoneum in a series of guinea-pigs. By the latter 

 method the virulence after a time is increased twenty-fold — that 

 is, the fatal dose has been reduced to a twentieth of the original. 

 Cultures treated in this way constitute the virus exalte. Subcu- 

 taneous injection of the virus exalte produces a local necrosis, 

 and may be followed by the death of the animal, but if the 

 animal be treated first with the attenuated virus, the subsequent 

 injection of the virus exalte produces only a local oedema. After 

 inoculation first by attenuated and afterwards by exalted virus, 

 the guinea-pig has acquired a high degree of immunity, and 

 Haffkine believed that this immunity was effective in the case 

 of every method of inoculation, that is, by the mouth as well as 

 by injection into the tissues. After trying his method on the 

 human subject and finding it free from risk, he extended it in 

 practice on a large scale in India in 1894, and these experiments 

 are still going on. So far the results are, on the whole, distinctly 

 encouraging. In the human subject two or sometimes three in- 



