396 INFECTION AND RESISTANCE 



ing at a time just preceding the occurrence of hemolysis (to exclude 

 the supposed toxic action of hemoglobin), and injected the super- 

 natant fluid of such mixtures into normal rabbits. The result was 

 marked illness resembling anaphylaxis, and Friedemann thus had 

 succeeded in producing the anaphylactic poison in vitro under con- 

 ditions as nearly as possible similar to those occurring in the circu- 

 lation of the anaphylactic rabbit. In the conclusions drawn from 

 his experiments he expresses the opinion that the poisons were not 

 preformed in the red blood cells, but were formed by the proteolysis 

 exerted by "amboceptor" and complement. In this statement he sets 

 down the basic conception of the production of anaphylactic poisons 

 now generally held. 



Friedemann, then, in attempts to apply the same methods to the 

 study of serum anaphylaxis, attempted to produce similar poisons 

 by the action of rabbit alexin upon the washed precipitates formed 

 by mixtures of antigen and precipitating sera. In this he failed 

 probably because of his choice of rabbits as subjects for experi- 

 ment. Where he had failed, however, Friedberger 39 succeeded 

 by using guinea pigs. Doerr and Russ 40 had previously shown 

 that feeble symptoms of shock could be produced by the injection 

 of serum precipitates into normal guinea pigs. With this addi- 

 tional evidence in favor of his reasoning, Friedberger pro- 

 ceeded as follows: 



One c. c. of a rabbit serum which precipitated sheep serum in a 

 dilution of 1 to 10,000 was mixed with 30 c. c. of a 1 to 50 sheep 

 serum dilution. This was kept one hour at 37.5 C. and over night 

 in the ice-chest, when a heavy flocculent precipitate had formed. 

 This precipitate was washed to remove all traces of serum, and to it 

 were added 2 c. c. of fresh normal guinea pig serum as comple- 

 ment. This was again allowed to stand for 12 hours and then the 

 supernatant fluid was injected into a guinea pig intravenously. In 

 most cases the pigs so treated showed marked symptoms soon after 

 the injection and died within a few hours. 



Friedberger concludes, therefore, that anaphylactic shock is a 

 true intoxication due to a poison produced from the products of a 

 precipitin-precipitinogen reaction by the action of a complement; 

 he speaks of the formed poison as anaphylatoxin. The experiment 

 just outlined, moreover, seems to show, contrary to Friedberger ? s 

 first ideas, that the entire reaction may go on under certain circum- 

 stances in the blood stream without intervention of sessile precipitins 

 upon the cells. 



We have, thus, in the cited work of Friedberger the culmination 

 of a long series of investigations the end result being the conclusion 



39 Friedberger. Berl klin. Woch., 32 and 42, 1910; also Zeitschr. f. 

 Immunitatsforsch., Vol. 4, 1910. 



* Doerr and Russ. Zeitschr. f. Immunitatsforsch., Vol. 3, p. 181, 1909. 



