28 APPLIED IMMUNOLOGY 



One of the earliest investigators to devote special at- 

 tention to this subject was Richet. He injected an 

 animal with a dose of protein poison, and after com- 

 plete recovery from the symptoms produced, by inject- 

 ing a very much smaller dose which in a non-sensitized 

 animal would have no deleterious effects, was able to 

 cause death in a few hours. This hypersusceptibility 

 in the sensitized animal Richet ascribed to the forma- 

 tion of a special antibody by the first injection, which 

 on the second injection causes the splitting off of a 

 highly toxic substance from the toxin injected, giving 

 rise to the symptoms. Richet's conclusions were based 

 on the assumption that the phenomena only occurred 

 when toxic substances were injected. Arthus in 1903 

 showed that hypersusceptibility occurred when non- 

 toxic protein material was used, such as normal horse 

 serum, milk, etc. (Arthus' phenomenon). He also 

 showed that the symptoms could only be produced by 

 means of the same substance that w^as originally in- 

 jected; e.g. J that an animal first sensitized with horse 

 serum would not be affected with a subsequent in- 

 jection of milk or other protein material, but only 

 with horse serum. The studies of von Pirquet showed 

 that a certain interval must elapse after the first in- 

 jection of serum before a second injection will pro- 

 duce s}Tnptoms, and he concluded that this interval 

 represented a period of incubation necessary for anti- 



