360 INFECTION AND RESISTANCE 



systematic and purposeful study of the problem was deferred until 

 Eichet and Portier 3 attacked it in 1902. 



Richet and Hericourt 4 had observed in 1898 that dogs treated 

 with eel serum, which is toxic per se, could be killed by a second 

 injection of an amount too small to injure normal untreated animals. 

 Some years later Richet, in collaboration with Portier, 5 determined 

 a similar fact in the case of a poisonous substance, "actinocongestin," 

 which they isolated by extraction of the tentacles of actinia. 



Some of the facts of Richet and Hericourt's observations are as 

 follows: Actinocongestin injected intravenously into dogs in quan- 

 tities of 0.05 to 0.075 gram per kilo weight may cause illness, with 

 vomiting, diarrhea, and respiratory distress, but does not kill. A 

 dose of 0.002 gram per kilo causes no symptoms in a normal dog. 

 If, however, 0.002 gram of the poison is injected into a dog which 

 has previously received a sublethal dose and recovered, the result 

 is violent illness and often death. It was obvious, and this was 

 clearly stated by Richet, that the first dose had induced a condition 

 of markedly greater susceptibility to the poison. 



He, therefore, spoke of the phenomenon as "anaphylaxis" ("ac- 

 tion anaphylactique de certains venins") to express its antithesis to 

 prophylaxis or protective effects. 



Although it has been disputed by a number of writers that 

 Richet's investigations constitute the beginnings of our modern 

 understanding of the anaphylactic phenomena, yet his recognition 

 of the distinct dependence of the hypersusceptible condition upon a 

 preceding inoculation with the same substance, and his conclusion 

 that a definite incubation time must elapse after the first injection 

 before susceptibility is developed, defined two of the most important 

 criteria of the condition and initiated purposeful investigations in 

 this field. It is true, on the other hand, that, like v. Behring and 

 most of his other predecessors, he was working with primarily toxic 

 substances, and the final recognition of the general biological sig- 

 nificance of the anaphylactic phenomenon was necessarily deferred 

 until a similar development of hyper susceptibility was noted in 

 animals injected with various antigens which of themselves were 

 entirely harmless. In this the history of anaphylactic investigations 

 is similar to that of other reactions to antigen injections, lysin, ag- 

 glutinin, and precipitin formation, in which the first observations 

 were made upon pathogenic bacteria or their products, and in which 

 subsequent extension of the investigations revealed that the response 

 to inoculation with bacterial proteins represented merely a single 

 phase of a general biological reaction on the part of animals to treat- 

 ment with the large class of substances known as antigens. 



3 Richet and Portier. C. E. de la Soc. BioL, p. 170, 1902. 



4 Richet and Hericourt. C. E. de la Soc. BioL, 1898. 



5 Portier and Richet. C. E. de la Soc. BioL, p. 170, 1902. 



