THE TOX7NES OF DIPHTHERIA. 341 



of the organisms could be detected by culture after twenty- 

 four hours. 



In rabbits after injection into the trachea and also after 

 subcutaneous injection, if the animals survive for some 

 time, paralytic symptoms may appear, and in a few days 

 gradually become more marked and lead to a fatal result, 

 death sometimes not occurring till the end of the fifth week. 

 This paralysis may also occur in dogs and other animals. 



In all these experiments, with the exception of Klein's 

 experiments on cows, the bacilli remained local. As the 

 symptoms of poisoning and ultimately a fatal result occur 

 when the bacilli are diminishing in number, or even after 

 they have practically disappeared, Roux and Yersin inferred 

 that the chief effects were produced by the products of the 

 organisms, and this supposition they proved to be correct 

 by a remarkable series of experiments with the filtered 

 cultures. 



The Toxines of Diphtheria. Roux and Yersin found as 

 above stated that a growth of virulent diphtheria bacilli in 

 broth produced at first an acid reaction, which was followed 

 later by a return to the alkaline condition. (Spronck, 

 however, has shown that when the broth is quite free from 

 glucose the acid reaction does not occur, and this is the 

 case when the meat from which the broth is made is kept 

 till traces of decomposition appear.) At the end of three 

 or four weeks, the reaction being then markedly alkaline, 

 the cultures freed from bacilli by filtration through a por- 

 celain filter were found to be highly toxic. The filtrate 

 when injected into guinea-pigs and other animals produces 

 practically the same effects as the living bacilli, with the 

 exception that locally there is no formation of false mem- 

 brane ; the internal organs show the same changes, and 

 locally there is inflammatory cedema, which may be 

 attended by a certain amount of necrotic change. The 

 toxicity may be so great that . i c.c. or even less may be 

 fatal to a guinea-pig in twenty-four hours. In rabbits, when 

 the dose is large, the intestines are found to be distended 

 with fluid, and there may be diarrhoea ; if the animals 



