394 INFECTION AND RESISTANCE 



cipitates into normal guinea pigs. With this additional evidence 

 in favor of his reasoning, Friedberger proceeded 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 

 iirst 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 

 that in all. probability at least as far as experimental ingenuity 

 has permitted us to penetrate into this very difficult problem up to 

 the present time the phenomenon of anaphylaxis must be regarded 

 as an acute intoxication, the poison which calls it forth being the 

 result of the union of an antigen and its antibody, the complex being 

 subsequently subjected to proteolysis by the action of alexin or com- 

 plement. The experimental extension of this conception to the phe- 

 nomena of bacterial anaphylaxis has promised to exert such an im- 

 portant influence upon our conceptions of infectious disease that we 

 will take up these investigations in a separate section. 



37 Here, then, we have a simple and apparently logical explanation 

 of anaphylaxis, entirely in accord with Vaughan's views of parenteral 

 digestion. An antigen is injected into an animal, specific antibodies 

 and enzymes against it develop in the animal ; reinjection of this 

 antigen results in relatively rapid proteolysis in the course of which 

 poisonous substances, the anaphylatoxins, are produced and anaphy- 

 laxis is the result. This hypothesis although very attractive does 

 not entirely meet with the facts as they have been developed since 

 Friedberger's first work. The premises on which it is based assume 

 in the first place that the poison or "anaphylatoxin" is formed out of 

 the matrix of the antigen ; further, it is definitely assumed that in the 



37 Much of this discussion is adapted from Zinsser, "More Recent De- 

 velopments in the Study of Anaphylactic Phenomena." Harvey Lecture 

 Arch, of Int. Med., Aug., 1915, Vol. 16, p. 223. 



