HYPERSENSITIVENKSS 471 



RiCHET AND Portier's Work. — Ricliet and Hericourt (1898) ob- 

 served that when dogs were injec?ted with eel serum, they became 

 sensitive to this material. Richet (1913) says that neither he and 

 Herieonrt, nor any of the othei-s who had in the past observed 

 sensitiveness, appreciated the sionificance of their observations. 

 It was not until he and Portier rediscovered and investiojated the 

 phenomenon in 1902 that its significance was appreciated. They 

 named this particular kind of hypersensitiveness "anaphylaxis" 

 since in their opinion it was the opposite of ''phylaxis" or pro- 

 tection. 



Arthus Phenomenon. — The following year (1903) Arthus ren- 

 dered rabbits hypersensitive to horse serum. He injected the 

 antigen subeutaneously into the animals at definite intervals and 

 observed that whereas the material comprising the first three in- 

 jections was rapidly absorbed, such was not true when later in- 

 jections were made. ?^ollowing these injections the material was 

 not a])sorbed and there developed at the site of inoculation definite 

 induration and not infrequently gangrene. Arthus also observed 

 general systemic reactions in rabbits that had received several 

 subcutaneous injections and finally an intravenous injection of 

 horse serum. He noted also that the reaction is specific since 

 he found that animals sensitized to horse serum are not sensitive 

 to milk and, conversely, animals sensitive to milk are not sensitive 

 to horse serum. 



The Theobald Smith Phenomenon. — In America, Theobald 

 Smith (1903) observed anaphylaxis in guinea pigs used to test 

 diphtheria antitoxin. He advised Ehrlieh of his observations and 

 the latter had Otto investigate the phenomenon. They were un- 

 aware of the earlier work of Richet and Portier. 



Rosenau's and Anderson's Studies. — Coincident with Otto's 

 invastigation, Rosenau and Anderson (1906) reported extensive 

 studies of anaphylaxis. The results of both investigations were 

 published almost simultaneously. Onh^ a few facts of funda- 

 mental importance relative to anaphylaxis in animals have been 

 added since these studies appeared. 



They determined that one injection of a nontoxic dose of horse 

 serum will render guinea pigs hypersensitive to a second injection 

 of the antigen provided an interval of almost ten days is allowed 



