ANAPHYLAXIS 397 



that they can be produced experimentally in the peritoneal cavity 

 of a living guinea pig renders their participation in such reactions in 

 the animal body a likely assumption. 



Our own work 41 on these substances induces us to believe that 

 proteotoxins so formed are identical with Bail's aggressins, a point 

 to which we will later refer. 



It is plain that the foregoing work has done away almost entirely 

 with the idea that anaphylactic phenomena were chiefly intravascular. 

 The brilliant experiments of Vaughan, of Friedemann, and of Fried- 

 berger seemed entirely convincing. They had succeeded in producing 

 a toxic substance apparently by cleavage of typical antigens in the 

 test tube by chemical and serological methods, and, on the face of it 

 there seemed no reason to doubt that such reactions might occur in 

 the circulating blood, thus explaining anaphylaxis. It has been on 

 the basis of the work of these pioneers, and experiments of others 

 based on the principles of this early work, that the intravascular 

 theories of anaphylaxis mechanism have been founded. For a time 

 these views held the center of the stage, and in their elaboration many 

 conditions were revealed which we believe have important bearing 

 on anaphylaxis in rabbits, perhaps in dogs, and in such special forms 

 of anaphylaxis as that produced by cellular antigens such as bac- 

 teria. However, from the beginning there have been irrefutable 

 experimental data which have prevented the complete acceptation 

 of the intravascular theory, indeed have caused it to seem likely that 

 in guinea pigs anaphylaxis was purely a cellular phenomenon and 

 that in anaphylaxis in general the intravascular occurrences were, 

 if at all important, secondary to the cellular mechanism. The most 

 important point which has always inclined workers to come back again 

 and again to the assumption of a participation of the body-cells, is 

 the necessary interval that must elapse (certainly in guinea pigs, and 

 with almost equal certainty in other animals) between the time of 

 injection of an antiserum, and the development of the anaphylactic 

 state in the animal. 



This observation, made by many of the earlier writers, has been 

 the crucial point of controversy not yet completely settled. The work 

 of Weill-Halle and Lemaire, which we have cited in a preceding- 

 section, seemed to show that the interval was not always necessary. 

 Richet, too, obtained experiments with crepitin which seemed to ex- 

 clude the necessity of the interval. It is interesting to note that he 

 spoke of his experiments as "reaction anaphylactique in vitro/' He 

 sensitized a dog to crepitin, then bled him during the hypersusceptible 

 period, mixed the serum with a harmless dose of crepitin, and in- 

 jected the mixture into a normal dog. Violent anaphylaxis resulted 

 almost immediately. 



At about the same time Friedemann published his very impor- 



41 Zinsser and Dwyer. Jour. Exper. Med., 1914, xx ; No. 6. 



