EARLY STUDIES OF V. PIRQUET 151 



of only 0.001 gram gave rise to this at once. In other words, at the 

 time of the second injection the animal was eighty times more 

 sensitive than before the first. Richet further showed that while 

 the primary injection produces no material effect upon the blood- 

 pressure the second injection is followed by a marked drop. 



Evidently then the first injection has in some manner called forth 

 a hypersusceptibility to the special toxin, which in the present 

 instance is characterized by an increased velocity as well as an 

 increased intensity of reaction. This type of hypersensitiveness, 

 Richet has termed anaphylaxis, indicating the absence of protection, 

 in contradistinction to prophylaxis or immunity. 



Arthus Phenomenon. The following year (1903) Arthus then 

 showed that similar results may be obtained with substances which, 

 unlike the actinocongestin, are altogether non-toxic. For on inject- 

 ing rabbits at definite intervals with normal horse serum, he found 

 that the first two or three doses were promptly absorbed, but that 

 subsequent injections led to increasingly more severe local reactions, 

 so that at times gangrene even developed. This occurred no matter 

 whether the injections were all made subcutaneously or the first ones 

 given intraperitoneally and only the last ones hypodermically. If 

 the animals, moreover, were first injected subcutaneously, and subse- 

 quently intraperitoneally or intravenously, serious general disturb- 

 ances (dyspnea, diarrhea, convulsions) and even death resulted 

 (Arthus phenomenon). Corresponding results were obtained with 

 milk, and Arthus could show that the anaphylactic reaction in ques- 

 tion was specific, as an animal that had been sensitized with horse 

 serum, for example, was not injured by the subsequent injection 

 of either milk, white of egg, or the serum of other animals, but 

 only of horse serum. 



Early Studies of v. Pirquet. Corresponding clinical studies were 

 undertaken almost simultaneously by v. Pirquet, and were based 

 upon the independent observation that a second injection of horse 

 serum in a child was not followed by symptoms of serum sickness 

 at the expiration of ten days, as had been noted after the first injec- 

 tion, but that they occurred in the course of the same day on which 

 the second injection was given. He concluded that the then existing 

 doctrine regarding the time of incubation in the different infectious 

 diseases was erroneous, and propounded the hypothesis that the 

 pathogenic agent calls forth symptoms of disease only after it has 



