318 TYPHOID FEVER. 



hour's exposure to a temperature of 60 C., must be em- 

 ployed. In the work of Brieger and Fraenkel, attended 

 as it was with unsatisfactory results, this mode of procedure 

 was not employed. 



The Immunisation of Animals against the Typhoid 

 Bacillus. In considering this difficult question the reader 

 must note (i) immunisation against the living bacilli; (2) 

 immunisation against their toxines ; and (3) the relations 

 between these two conditions. Earlier observers had been 

 successful in accustoming mice to the typhoid bacillus by 

 the successive injections of small and gradually increasing 

 doses of living cultures of the bacillus. Later, Brieger, Kita- 

 sato, and Wasserman, in their joint researches on immunity, 

 obtained further results. One of the general principles on 

 which they worked was that a bouillon made from an 

 extract of the thymus gland contained bodies which were 

 inimical to the virulence of various bacilli, though the 

 medium was sufficiently nutritive to permit of their multi- 

 plication. Applying this principle to the B. typhosus, they 

 grew a culture very virulent to mice for three days on such 

 a bouillon, and then killed the contained bacilli by heating 

 at 60 C. for fifteen minutes. A small quantity was then 

 injected into each of a series of mice without fatal effect. 

 Ten days later it was found that these mice could tolerate 

 an otherwise fatal dose of the original living virulent cul- 

 ture. The experiments were repeated on guinea-pigs with 

 a similar result, and it was also found that the serum of a 

 guinea-pig thus immunised could, if transferred to another 

 guinea-pig, protect the latter from the subsequent injection 

 of a dose of typhoid bacilli to which it would naturally 

 succumb. Chantemesse and Widal, Sanarelli, and also 

 Pfeiffer, succeeded in immunising guinea-pigs against the 

 subsequent intraperitoneal injection of virulent living typhoid 

 bacilli, by repeated and gradually-increasing intraperitoneal 

 orsubcutaneous doses of typhoid culturesin bouillon, in which 

 the bacilli had been killed by heat or chloroform vapour. 

 Experiments performed with serum derived from typhoid 

 patients and convalescents have been adduced as bearing 



