386 INFECTION AND RESISTANCE 



The point of their third argument has been discussed above. 

 It is clear that Gay and Southard separate distinctly the substance in the 

 antigen which sensitizes from that which exerts the toxic action on second injection. 



Another theory which is based on such a separation of a sensi- 

 tizing and shock-producing element in the original antigen is that 

 of Besredka. 



Besredka 5 assumes that in the injected antigen (serum) there are two 

 separate substances. One of these, the sensibilisinogen, induces, during the time 

 of incubation, a specific antibody (sensibilisin) . This antibody remains in part 

 attached to tissue cells and in part circulates freely in the blood. The other 

 substance in the antigen he calls " antisensibilisin." This, at the second injection, 

 reacts with the sensibilisin and anaphylactic shock results. The nature of the 

 symptoms is explained by the fact that the antibody or sensibilisin is attached to 

 cells of the central nervous system, and shock can result only when such attach- 

 ment is present. Thus, in passive transference of sensitization, the property of 

 hypersusceptibility is bestowed upon the normal animal by the sensibilisin or 

 antibody present in the circulating blood, but the significance of this body for 

 anaphylaxis is not in evidence until a connection with the central nervous system 

 has been established. 



There is much in Besredka's theory which is at variance with 

 prevailing conceptions of biological phenomena of this category. The 

 fact that an antigen should give rise to an antibody which reacts 

 not with the substance that induced it, but with a third body, is 

 quite out of keeping with experience. 



However, it is clear that in both theories, that of Gay and South- 

 ard, as well as that of Besredka, the cardinal point is this separa- 

 tion in the antigen of two substances, a sensitizing and a toxic or 

 shock-producing, and, since this forms the chief argument against an 

 antigen-antibody conception of anaphylaxis, it will be necessary to 

 examine the experimental evidence on which it is based. 



Gay and Adler 6 attempted to show such a dual function of the 

 original antigen by chemical methods. They report that, by frac- 

 tional precipitation of horse serum with ammonium sulphate, the 

 successive protein fractions obtained, as saturation is increased, are 

 found to be less sensitizing and more toxic as more and more am- 

 monium sulphate is added. The first fraction (euglobulins) obtained 

 by % saturation is as sensitizing as whole serum and corresponds to 

 anaphylactin, but is nontoxic when injected into sensitive animals. 

 The last fraction, while distinctly less sensitizing than either the 

 whole serum or the first fraction, is at least as toxic as the whole 

 serum. 



In these experiments, therefore, we have a strong argument in 

 favor of the separate presence in an anaphylactic antigen of two 

 bodies, the one sensitizing and the other toxogenic. However, this- 

 assertion has not been borne out by later work. 



5 Besredka. Loc. cit. 



6 Gay and Adler. Jour. Med. Res., Vol. 13, 1908. 



