HYPERSUSCEPTIBILITY 219 



of incubation and forms a toxic substance named apotoxlne. He com- 

 pares the reaction to the combination of amygdaline and emulsine to 

 produce hydrocyanic acid. This hypothesis resembles somewhat that 

 of Friedberger, which has been investigated intensively by many 

 workers. Friedberger prepared a toxic substance, which he named 

 anaphylatoxin, by mixing antigen, precipitating serum and complement. 

 He obtained a precipitate by mixing sheep serum with a specific immune 

 precipitating serum from the rabbit. This precipitate was washed, sus- 

 pended in fresh guinea-pig serum for twelve hours, then centrifuged. 

 The supernatant fluid was found to be extremely toxic for guinea-pigs. 

 The reduction of complement in anaphylaxis has been emphasized by 

 Friedberger in the development of his hypothesis concerning ana- 

 phylatoxin. Thomson, however, has found that this reduction is not 

 constant and that it is in proportion to the quantity of the free antibodies 

 in the circulation. It is insignificant when the animal has been sensi- 

 tized with a small single dose of antigen, but if the animal has been 

 sensitized by repeated doses and the precipitin content of the blood is 

 high, the diminution in complement is likely to be marked. The symp- 

 toms following injection of anaphylatoxin include the usual clinical 

 manifestations, with fall of temperature, retardation of coagulation of 

 the blood and leucopenia. The poison resists heat at 56 C. for one-half 

 hour, resists desiccation and is precipitated by alcohol. Subsequently 

 it was found that bacteria and their antisera could be employed in the 

 same fashion as the precipitinogen and precipitin. Doerr and Russ 

 found that precipitates are toxic without the addition of complement, 

 and in view of this fact and the production of passive anaphylaxis by 

 precipitating sera, reached the conclusion that precipitin and the sub- 

 stance produced by the primary injection in anaphylaxis are inseparable. 

 Kraus and his co-workers have contradicted this parallelism and point 

 out that the guinea-pig is a poor producer of precipitin; rabbits may 

 produce a powerful anaphylactic substance without producing precipi- 

 tins; goats produce precipitin readily but have a serum incapable of 

 conferring passive anaphylaxis. Biedl and Kraus pointed out the fact 

 that injections of pepton produce symptoms similar to anaphylaxis in 

 the dog. Karsner has confirmed this in the guinea-pig. Biedl and 

 Kraus found that following injection of pepton into a dog the animal 

 subsequently fails to react to anaphylaxis and hence they formulatedV. 

 the hypothesis that the poison of anaphylaxis is a pepton-like body. 

 Doerr offered the hypothesis that the actual disturbance is in the physi- 

 cal character of the blood. He assumes, however, that this disturbance 

 is produced by a toxic agent originating in complement. The com- 

 plement is supposed to contain the toxic substance held in check by an 

 antagonistic substance ; the latter is adsorbed by precipitates or bacteria, 

 thus liberating the toxic substance. The further investigation of the 

 so-called anaphylatoxin led to the discovery by Keysser and Wasser- 

 mann that a similar substance could be produced by the action of com- 

 plement on barium sulphate or kaolin. Besredka then found that placing 

 fresh serum upon pepton agar produces a toxic fluid which induces 



