ANAPHYLAXIS 395 



production of the poison after the antigen and antibody have met, the 

 complement or alexin plays an active part. Friedberger's hypothesis 

 as stated by him, moreover, seems to assume that the entire process 

 takes place intravascularly, a matter which we will discuss at consid- 

 erable length in a short time. It is important to note also that Fried- 

 berger, with Nathan, was able to show that this anaphylatoxin produc- 

 tion could take place within the animal body ; that is, within the peri- 

 toneum of a guinea-pig into which bacteria had been injected. 



The simplicity of Friedberger's explanation and the correctness 

 of his experimental data soon persuaded many investigators that, in 

 essence, his hypothesis probably contained the nucleus of the solution 

 of this difficult problem. However, even his own early experiments 

 aroused some misgivings concerning the matrix of the poisons pro- 

 duced, for he found that the poisons could be obtained as well when 

 boiled antigen was used as when the fresh, unheated substances were 

 employed, and the poisons were easily obtained from such organisms 

 as the tubercle bacillus, which is extremely insoluble and unamenable 

 to serum influence. It was also doubted whether one could truly 

 assume the participation of this specific antibody or sensitizer in the 

 production of Friedberger's poisons, since it soon developed that from 

 bacteria, at least, the poison could be produced when the organisms 

 were directly exposed to the action of fresh guinea-pig serum without 

 the presence of any immune serum. 



Experiments which soon cast a definite doubt on the assumption 

 that the poisons were produced by a decomposition of the antigen 

 were reported by Keysser and Wassermann, 38 These workers sub- 

 stituted insoluble substances like barium sulphate and kaolin for the 

 antigen; that is, the precipitates or bacteria used in Friedberger's 

 experiments. They found that if kaolin were treated with horse 

 serum and, then exposed to the action of guinea-pig serum or comple- 

 ment, poisons were produced identical in every respect to those pro- 

 duced by Friedberger's method. The conclusions they drew were 

 that the poisons were produced, not by action of the complement on 

 the antigen, but by its action on the horse serum absorbed by the 

 kaolin. In other words, they transferred the matrix of the poison 

 from the antigen to constituents in the serum itself, possibly the 

 sensitizer or amboceptor. Bordet 39 also was able to show that poisons 

 similar to those of Friedberger could be produced by the action of 

 fresh guinea-pig serum on agar, and recently Bordet has further 

 shown that this is the case even when the agar has been by special 

 methods deprived entirely of its nitrogenous components and repre- 

 .sents simply a complex of carbohydrates. Agar-guinea-pig serum 

 mixtures of this kind show an increase in total nonprotein nitrogen 



38 Keysser and Wassermann. Folia serol, 1911, vii; Ztschr. f. Hyg. u. 

 Infectionskrankh., 1911, Ixviii. 



39 Bordet. Compt. rend. Soc. de biol, 1913, Ixxiv, 877. 



