BACILLUS OF TYPHOID FEVER 425 



paratively easy to immunize animals actively against typhoid infection 

 by the systematic injection of graded doses, at first of dead bacilli, later 

 of fully virulent live cultures. Attempts to apply these principles pro- 

 phylactically have been made recently on a large scale by Wright and 

 his associates upon English soldiers in South Africa, and by German 

 observers in German East Africa. 



The first recorded experiment of this sort which was done upon human 

 beings was that of Pfeiffer and Kolle,' who in 1896 treated two in- 

 dividuals with subcutaneous injections of an agar culture of typhoid 

 bacilli which had been sterilized at 56° C. The first injection was made 

 with two milligrams of this culture. Three or four hours after the in- 

 jection the patient suffered from a chill, his temperature gradually rose 

 to 105° F., and there was great prostration and headache, but within 

 twenty-four hours the temperature had returned to normal. 



This experiment showed that such injections could be practiced upon 

 human beings without great danger. 



Simultaneously with the work of Pfeiffer and Kolle, Wright ^ con- 

 ducted similar experiments on officers and privates in the English army. 



The actual number of persons treated directly or indirectly under 

 Wright's ^ supervision in an investigation covering a period of over four 

 years comprised almost one hundred thousand cases. The methods 

 employed by Wright have been modified several times by him and his 

 collaborators in minor details; the principles, however, have remained 

 consistently the same. In the first experiments Wright employed an 

 agar culture three weeks old, grown at 37° C, then sterilized at a tem- 

 perature below 60° C, and protected from contamination by the ad- 

 dition of five-tenths per cent of carbolic acid. Later, Wright ^ employed 

 bacilli grown in a neutral one-per-cent pepton bouillon in shallow layers 

 or flasks. Great importance is attached both to the virulence of the ty- 

 phoid strain, which may to a moderate extent be standardized by pas- 

 sage through guinea-pigs, and to care in using low temperatures 

 for final steriUzation. The temperature recommended by Harrison,^ 

 working with Wright's method, is 52° C., after which the cultures are 

 carbolized. For the first dose in a human being, Wright recommends 



' Pfeiffer und Kolle, Deut. med. Woch., xxii, 1896; xxiv, 1898. 

 ^Wright, Lancet, Sept., 1896. 



3 Wright and Semple, Brit. Med. Jour., 1897; Wright and Leishman, Brit. Med. 

 Jour., Jan., 1900. 



* Wright, Brit. Med. Jour., 1901; Lancet, Sept., 1902; Brit. Med. Jour., Oct., 1903. 

 ''Harrison, Jour. Royal Army Medical Corps, 1907. 



