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 Pfciffer and Kolle, 1 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 2 con- 

 ducted sim^ar experiments on officers and privates in the English army. 



The actual number of persons treated directly or indirectly under 

 Wright's 3 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 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 temperature below 60 C., and pro- 

 tected from contamination by the addition of five-tenths per cent of 

 carbolic acid. Later, Wright 4 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 typhoid 

 strain, which may to a moderate extent be standardized by passage 

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

 sterilization. The temperature recommended by Harrison, 5 is 52 C., 

 after which the cultures are carbolized. 



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



2 Wright, Lancet, Sept., 1896. 



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

 Jour., Jan., 1900. 



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

 1903. 



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



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