514 APPLICATION OF METHODS OF BACTERIOLOGY 



genuine infection. 1 These diversities of opinion are hardly 

 surprising when we remember that animals never suffer 

 naturally from typhoid fever, and therefore offer many 

 obstacles to its faithful reproduction, and that the vigor of 

 this organism when cultivated from various sources is liable 

 to a wide range of fluctuation. Numerous investigations 

 lead to the belief that the poison peculiar to this organism 

 is so intimately bound up with its protoplasmic structure 

 as to make its separation difficult, if not impossible. How- 

 ever, by the use of dead cultures (i. e., cultures of well 

 developed organisms destroyed by heat) results are obtained 

 that leave no doubt that the clinical symptoms and patho- 

 logical changes seen in man and in animals under experiment 

 are referable to a specific intoxication, and, as a rule, the 

 only effects that follow the introduction of this organism 

 into animals are referable to the intoxicating action of the 

 materials used. In fact, the results of modern investigations 

 have placed bacillus typhosus in the category of endotoxin 

 producers, and through the use of the toxins (not pure, but 

 mixed with other substances in the culture media) produced 

 by it animals have been rendered immune from otherwise 

 fatal doses of highly toxic cultures. The serum of such 

 animals has also been shown to possess a certain degree of 

 immunizing power. 2 



Because of the variations in the morphology and physiology 

 of this organism, and because of the difficulty experienced 

 in efforts to reproduce in lower animals the condition 

 found in the human subject, our knowledge of typhoid 

 fever, though fairly accurate in many respects, is, never- 



1 Infective or septic poisoning of the tissues as a result of the growth 

 of bacteria within them. 



2 Pfeiffer and Kolle, Zeitschrift fur Hygiene und Infektionskrankheiten 

 1896, Bd. xxi, S. 208. 



