466 IMMUNITY. 



and by increasing the doses, a high degree of immunity 

 may be arrived at. 



Anti-Cholera Inoculation. Haffkine's method for in- 

 oculation 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 of passage, that is, by growing the organism 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. Subcutaneous 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, encouraging. In the human 

 subject two or sometimes three inoculations are made with 

 attenuated virus before the virus exalte is used. Wasser- 

 mann and Pfeiffer, and also Klein, have found, however, 

 that guinea-pigs immunised by Haffkine's method are not 

 immunised against intestinal infection when the animal is 

 treated by Koch's method (that is, by paralysing the 

 intestines with opium, vide p. 413). Notwithstanding this 

 fact Haffkine's method may still have a beneficial effect, 

 though it may not be preventive in all cases. 



2. Immunity by Dead Cultures of Bacteria. In some 



