216 PROTEIN POISONS 



The fact that animals which have once received an 

 injection of protein are liable to sudden death after a second 

 injection of the same kind has been known for many years. 

 Ever since the opening of the Hygienic Laboratory of the 

 University of Michigan (1888), animals once used have 

 been segregated and kept in cages marked "used animals," 

 which indicated that conclusions could not be safely drawn 

 from results obtained when these animals were employed a 

 second time. In the standardization of diphtheria antitoxin 

 it soon became evident that the guinea-pigs that survived 

 one test could not be relied upon in a second one. In the 

 late nineties, Parke, Davis & Co., large manufacturers of 

 antitoxins, ascertained this fact and offered to supply the 

 Hygienic Laboratory of the University of Michigan with 

 " used" guinea-pigs at a small price. The offer was accepted, 

 but the animals were found dear at any price, as they 

 suddenly and unexplainably died when treated with horse 

 serum. 



This condition evidently was observed by others, and 

 Theobald Smith mentioned it to Ehrlich, who set Otto to 

 work to find the explanation. Otto 1 published his results 

 under the title "Das Theobald Smithsche Phanomen der 

 Serumiiberempfindlichkeit." However, simultaneously with 

 these observations on animals used in the standardization 

 of antitoxin, the profession had occasion to observe the 

 effects of injections of antitoxin in human beings. As 

 early as 1903, v. Pirquet 2 wrote concerning certain clinical 

 effects following antitoxin treatment, and in 1905 he and 

 Shick published a monograph "the serum disease," "Die 

 Serumkrankheit. ' ' 



Definition. Friedemann 3 offers the following definition: 

 "We speak of anaphylaxis when the organism, in conse- 

 quence of a previous treatment with an antigen, after a 

 period of incubation becomes hypersensitive to the same 

 or to a closely related substance, and when this condition 



1 V. Leuthold Gedenkschrift, 1906. 



a Wien. klin. Woch. 



3 Jahresb. u. d. Ergeb. d. Immunitatsforschung, 1910, vi. 



