INTRODUCTION. 11 



It may also be mentioned that the formation of precipitates, which takes 

 place when the serum of injected rabbits and venom are mixed, may possibly 

 account for a slight decrease in the toxicity of the venom, occasionally noticed 

 after addition of venom to the serum of rabbits immunized against venom. 

 We may assume that this precipitate included a certain portion of the venom 

 and thus retarded its absorption and exerted a very slight protective influence. 

 An antivenin which, according to Phisalix, is responsible for the natural im- 

 munity of some poisonous animals against their own venom, can not be found 

 in the blood of Heloderma, as we have already mentioned. Neither does the 

 blood-serum of Heloderma contain any substance which fixes complement in 

 combining with a constituent of the heloderma venom (E. P. Corson-White). 

 Venom itself, however, is capable of binding a considerable quantity of com- 

 plement in a similar manner, as has been found in the case of snake venoms. 

 It appears doubtful whether this effect is due to the toxic substance proper or 

 to admixed proteid material. After repeated injections of venom, symptoms 

 of general anaphylaxis could not be observed. The sterile abscesses which 

 appear in animals that have received frequent injections of heloderma venom 

 may perhaps represent a local anaphylactic reaction related to the Arthus phe- 

 nomenon, to which a similar reaction observed after injection of snake venom 

 had indeed been compared by previous investigators. 



In this case also the reaction is perhaps not due to the toxin proper, but to 

 the proteid material admixed with the venom ; and this reaction could therefore 

 be in part avoided, perhaps, if the filtered fluid only were injected without the 

 precipitate found on heating, a procedure which entails a certain loss of venom, 

 inasmuch as the precipitate includes some toxin which has been adsorbed. 



The specificity of antivenin against snake venoms has been an object of 

 much controversy. We thought it therefore of sufficient interest to inves- 

 tigate the effect of Calmette's cobra antivenin upon the venom of Heloderma. 

 Both the venom of Heloderma and of Cobra are essentially neurotoxic and 

 secondarily hemolytic. Both venoms are therefore very similar in their effect 

 upon animal tissue. On the other hand, Heloderma is systematically less 

 nearly related to the Cobra than any of the snakes. Inasmuch as it has been 

 maintained that even among snakes the various neurotoxins are specifically 

 different and that cobra antivenin neutralizes mainly the venom of cobra, it 

 was not probable that cobra antivenin would exert any influence upon helo- 

 derma venom; but our investigations leave little doubt that Calmette's cobra 

 antivenin does exert antitoxic effect upon heloderma venom. This action is, 

 however, very slight and naturally very much less marked than in the case of 

 cobra venom. Our observations confirm, therefore, the belief that there exists 

 a graded specificity, and also prove that this specificity is less limited than has 

 been assumed by various investigators. 



The difference in the heat-resistance between the neurotoxin of heloderma 

 and of cobra venom makes it very improbable that both substances are iden- 

 tical, although they may be related to each other. The results of Faust r 

 which show a difference in the constitution of ophiotoxin and of crotalotoxin, 

 make this conclusion almost certain. 



