THE TOXINES OF DIPHTHERIA. 365 



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. 

 They showed that broth cultures of three or four weeks' 

 growth freed from bacilli by filtration were 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 forma- 

 tion of false membrane ; the internal organs show the 

 same changes, and locally there is inflammatory oedema, 

 which may be attended by a certain amount of necrotic 

 change. The toxicity may be so great that .05 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 survive for two or three days 

 there is usually albuminuria, and, post mortem, nephritis is 

 found to be present. 



After injection either of the toxine or of the living 

 bacilli, when the animals such as guinea-pigs, rabbits, dogs, 

 etc., survive long enough, paralytic phenomena may occur. 

 The hind limbs are usually affected first, the paralysis 

 afterwards extending to other parts, though sometimes the 

 fore-limbs and neck first show the condition. Sometimes 

 symptoms of paralysis do not appear till two or three weeks 

 after inoculation. After paralysis has appeared, a fatal 

 result usually follows in the smaller animals, but in dogs 

 recovery may take place. One point of much interest in 

 relation to the relative nature of toxicity is the high degree 

 of resistance to the toxine possessed by mice and rats. 

 Roux and Yersin, for example, found that 2 c.c. of toxine, 

 which was sufficient to kill a rabbit in sixty hours, had no 

 effect on a mouse, whilst of this toxine even T V c.c. pro- 

 duced extensive necrosis of the skin of the guinea-pig. 



Preparation of the Toxine. The obtaining of a very 

 active toxine in large quantities is an essential in 

 the preparation of anti- diphtheritic serum. Certain 



