THE TOXINS OF DIPHTHERIA 361 



the contagion was apparently carried by the milk. Other observers 

 have, however, failed to obtain similar results. Dean and Todd, in 

 investigating an outbreak of diphtheria traceable to milk supplied, 

 found a vesicular eruption on the teats of the udder in which diphtheria 

 bacilli were present. They, however, came to the conclusion that these 

 bacilli were not the cause of the eruption, but were the result of a 

 secondary contamination, probably from the saliva of the milkers. The 

 occurrence of a true infection with the diphtheria bacillus in the horse 

 has been described by Cobbett. 



The Toxins of Diphtheria. As in the above experiments 

 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 toxins, 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 nitrate when injected into guinea-pigs and other 

 animals produces practically the same effects as the living bacilli ; 

 locally there is fibrinous exudation but a considerable amount 

 of inflammatory cedema, and, if the animal survive long enough, 

 necrosis in varying degree of the superficial tissues may follow. 

 The toxicity may be so great that "01 c.c. or even less may be 

 fatal to a guinea-pig in twenty-four hours. 



After injection either of the toxin or of the living bacilli, 

 when the animals 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. There is evidence that these paralytic phenomena 

 are produced by toxone (p. 171), as they may occur when there 

 is injected along with the toxin sufficient antitoxin to neutralise 

 the more rapidly acting toxin proper. This toxone is supposed 

 by Ehrlich to have a different toxic action, i.e. a different 

 toxophorous group, from that of the toxin, and to have a weaker 

 affinity for antitoxin ; much of it may thus be left unneutralised. 

 It is to be noted in this connection that paralytic symptoms are 

 of not uncommon occurrence in the human subject after treatment 

 with antitoxin, the explanation of which occurrence is probably 

 the same as that just given. One point of much interest is the 

 high degree of resistance to the toxin possessed by mice and 

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

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



