SPECIFICITY AND THERAPEUTIC VALUES OP ANTIVENINS 237 



theless it was some time before accurate differentiation of these toxins could 

 be realized. At present we are still far from being in a position to analyze 

 the exact cause of this individual difference in these seemingly identical 

 cytotoxins. Specificity, as we understand it from the immunity reactions, 

 is still an unknown factor and, beyond perceiving the fact as it is, we have 

 no right to infer an absolute difference. In fact, it is not at all improbable 

 that specificity is nothing but the expression of the variable surroundings 

 amidst which venom toxins coincidentally exist. 



The work of Faust demonstrated the probability that venom toxins exist 

 in a native state as ester-like compounds of proteins. If this assumption is 

 correct the venom immunity reactions would correspond to the protein im- 

 munity reactions, to which the well-known precipitation and complement- 

 deviation phenomena properly belong. Again, it is remarkable that immunity 

 reactions are obtainable only when antigens of colloidal character are injected. 

 This consideration may not be out of place here, bcause we may in the future 

 be able to modify the toxin molecules in such manner that they become non- 

 toxic without altering the radicals responsible for the production of anti- 

 toxins, as was done by Flexner and Noguchi with the haemorrhagins — toxoid 

 formation in Ehrlich's sense. 



In the following pages I will detail some of the more important investiga- 

 tions concerning the specificity of different type toxins of venoms. 



In 1899 Stephens observed that Calmette's antivenin could neutralize the 

 haemolytic principle of cobra venom, but failed to do so when tested against 

 the haemolysins contained in daboia venom and crotalus venom. He there- 

 fore suggested that the haemolysins of different venoms, hence snake toxins, 

 as a class, are not identical with each other. Having had no pure antivenins 

 he could not pursue this particular point farther. 



The more accurate determination of this species specificity of venom 

 cytotoxins calls for the employment of pure antivenins, that is to say, anti- 

 venins produced by injecting pure venoms of different species. With such 

 antivenins we can determine whether the antivenin produced with venom 

 A can neutralize venom B or C. Inversely, the action of venom A can be 

 tested with the antivenins produced with venom B or C, and so on. 



Up to the present time eight pure antivenins have been produced, namely: 

 (1) Daboia antivenin (Lamb) ; (2) Crotalus adamanteus antivenin (Flexner 

 and Noguchi); (3) Crotalus terrificus antivenin (Brazil); (4) Ancistrodon 

 piscivorus antivenin (Noguchi); (5) Lachesis lanceolatus antivenin (Brazil); 

 (6) Lachesis fiavoviridis antivenin (Kitashima, Ishizaka); (7) Notechis scu- 

 tatus antivenin (Tidswell); (8) Cobra antivenin (Lamb). 



The work of Lamb has been most extensive and systematic and has con- 

 tributed much to our knowledge concerning this particular phase of venom 

 immunity, while the results obtained by other investigators have assisted in 

 settling the question of individual specificity of type toxins. For the sake 

 of clearness and brevity the results of their investigations are presented in 

 tables 21 and 22. 



