EXPERIMENTAL INOCULATION. 383 



cellular degenerations the cells have been observed to return 

 to the normal under the curative influence of the antitoxins 

 (vide infra). In the other organs of the body there are no 

 constant changes. 



We have said that the general distribution of pathogenic 

 bacteria throughout the body is probably a relative phenomenon, 

 and that bacteria usually found locally may occur generally, and 

 vice versa. With regard to the tetanus bacillus it is, however, 

 probably the case that very rarely, if ever, are the organisms 

 found anywhere except in the local lesion. 



(b) The Artificially-produced Disease. The disease can be 

 communicated to animals by any of the usual methods of inocu- 

 lation, but does not arise in animals fed with bacilli, whether 

 these contain spores or not. Kitasato found that pure cultures, 

 injected subcutaneously or intravenously, caused death in mice, 

 rats, guinea-pigs, and rabbits. In mice, symptoms appear in a 

 day, and death occurs in two or three days, after inoculation 

 with a loopful of a bouillon culture. The other animals men- 

 tioned require larger doses, and death does not occur so rapidly. 

 Usually in animals injected subcutaneously the spasms begin 

 in the limb nearest the point of inoculation. In intravenous 

 inoculation the spasms begin in the extensor muscles of the 

 trunk, as is the case in the natural disease in man. After death 

 there is found slight hyperaemia, without pus formation, at the 

 seat of inoculation. The bacilli diminish in number, and may 

 be absent at the time of death. The organs generally show 

 little change. 



Kitasato states that in his earlier experiments the quantity of 

 culture medium injected along with the bacilli already contained 

 enough of the poisonous bodies formed by the bacilli to cause 

 death. The symptoms came on sooner than by the improved 

 method mentioned below, and were, therefore, due to the toxins 

 already present. In his subsequent work, therefore, he em- 

 ployed splinters of wood soaked in cultures in which spores 

 were present, and subsequently subjected for one hour to a 

 temperature of 80 C. The latter treatment not only killed all 

 the bacilli, but, as we shall see, was sufficient to destroy the 

 activity of the toxins. When such splinters are introduced 

 subcutaneously, death results by the development of the spores 

 which they carry. In this way he completed the proof that 



