TOXINS AND ANTITOXINS 243 



in the mouse and the rat is probably due to tissue insusceptibility. 

 They do not possess antitoxin, and no other substance has been 

 found that will explain their refractoriness to diphtheria toxin. 

 According to Coca (1925) toxin circulates when injected into the 

 blood stream of the rat without being either detoxified or combined 

 with the tissues. Coca, Russell, and Baughman (1921) as well 

 as Glenny and Allen (1922) have shown that exceedingly large 

 doses are toxic. It should be remembered that it is impossible to 

 prepare pure toxin and that the toxin injected is present in the 

 filtrate of a broth culture that is at least seven to ten days old. 

 This contains autolysed products of bacteria, by-products of 

 metabolism other than toxin as well as the latter and also various 

 ingredients of culture media. It is to be expected that large 

 amounts of such a complex pharmacological product might pro- 

 foundly affect many physiological mechanisms that may be in- 

 volved in the maintenance of a refractory state to one ingredi- 

 ent, toxin. 



Symptoms in Susceptible Animals. — If a susceptible animal 

 such as a rabbit or guinea pig is given a subcutaneous injection 

 of a fatal dose of either a virulent culture or of toxin alone, one 

 observes a fairly definite train of symptoms. There is always an 

 incubation period of several hours which varies with the virulence 

 of the organism or amount of toxin and the size and age of the 

 animal. The significance of the incubation period is unknown. It 

 is generally assumed that this represents the time necessary for 

 the toxin to reach and be bound by the tissues. Richet, accord- 

 ing to Zinsser (1931) suggests that the toxin is not poisonous until 

 acted upon by the body. The selective action of toxin has been ex- 

 plained by assuming a difference of chemical affinity for or of 

 solubility in the various tissues of the body. 



Pathology in Lower Animals. — After twelve, fifteen, or twenty 

 hours or even several days, where the dose is small, the animals 

 develop an inflammatory edema and necrosis at the point of in- 

 oculation. This is destined to show definite extension. Simul- 

 taneously with the development of the reaction at the point of 

 inoculation, the animal also shows clinical evidence of illness. 

 It becomes quiet, the coat is roughened, there is some tempera- 

 ture change and weight loss as well as loss of appetite. Death 

 may be made to occur within four or five days if the proper dose 



