388 INFECTION AND RESISTANCE 



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 remained unchallenged. 



Pick and Yamanouchi, 7 whose extensive investigation cannot be 

 fully reviewed here, were unable to obtain such a separation; in 

 fact, they conclude that the same substances which sensitize are also 

 toxic, and, working with a large variety of methods, find that both 

 the sensitizing and toxogenic properties of proteins show no differ- 

 ences either in chemical condition or in resistance to chemical agents 

 or heat. 



The work of Pick and Yamanouchi, however, was done with 

 rabbits and, therefore, as bearing on the theory of Gay and Southard, 

 the work of Doerr and Russ 8 is more directly to the point. These 

 workers using guinea pigs, and both horse and beef sera, obtained 

 results which are practically diametrically opposed to those of Gay 

 and Adler. They found that the euglobulins, obtained by % satura- 

 tion with ammonium sulphate, are the most strongly sensitizing and, 

 at the same time, the most toxic of the fractions of the sera. As 



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



7 Pick and Yamanouchi. Zeitschr. f. Immunitatsforschung, 1, 1909. 



8 Doerr and Russ. Zeitschr. f. Immunitatsforschung, Vol. 2, 1909. 



