202 THE VENOM OF HELODERMA. 



it is not so poisonous as the latter, if equal amounts of the mixture which is 

 called venom are compared. Cobra antivenin should therefore exert a powerful 

 protecting influence against the venom of heloderma. On the other hand, from 

 the point of view of zoological relationship, Heloderma is further distant from 

 the Cobra than any snake. According to the prevalent view cobra antivenin 

 should be without any effect on the venom of heloderma. 



In our experiments we used a cobra antivenin which Doctor Calmette 

 kindly put at our disposal; 1 c.c. of this antivenin was sufficient to neutralize 

 1 mg. of cobra venom (tested by Doctor Calmette) ; 0.01 mg. of cobra venom is 

 a dose lethal for a white mouse; 1 c.c. of Calmette's serum neutralizes, there- 

 fore, 100 lethal doses. We used white mice in our experiments. In all cases a 

 definite quantity of dry venom and Calmette's serum were mixed in vitro. 

 The mixture, having stood 45 minutes at room temperature, was injected into 

 the mice subcutaneously. In control experiments mice were injected with 

 mixtures of venom and 0.85 per cent NaCl solution, or rabbit serum, horse 

 serum, and diphtheria antitoxin. None of these latter substances exerted any 

 protecting influence. In another experiment less than a lethal dose of helo- 

 derma venom was used (namely, 0.1 mg.), and it was found that rabbit serum 

 did not increase the toxicity of heloderma venom. Cobra antivenin, on the 

 other hand, had a definite though very slight antitoxic effect on heloderma 

 venom; it is able to neutralize a fraction of a lethal dose. After the addition of 

 cobra antivenin a certain number of mice died as quickly under the influence of 

 heloderma venom as the control mice injected with venom plus 0.85 per cent 

 NaCl solution. In each experiment there were, however, others in which the 

 antivenin delayed the appearance of the heloderma- venom poisoning; 40 per 

 cent of the animals injected with one or two lethal doses of heloderma venom 

 mixed with either 0.5 or 0.75 c.c. of cobra antivenin survived, while all the con- 

 trols died. If more than one or two lethal doses of heloderma venom were used, 

 0.5 c.c. of cobra antivenin was without effect. In an experiment in which the 

 antivenin and the heloderma venom were injected at different places without 

 having been previously mixed in the test-tube, merely a delay in the lethal 

 action was noticeable. 



In an experiment the mixture was kept in the thermostat, and the venom 

 underwent some deterioration, in consequence of which some of the control 

 mice survived. This experiment is, therefore, inconclusive. 



Although the action of Calmette's cobra antivenin on heloderma venom is 

 very slight, the serum neutralizing only a fraction of a lethal dose, there can be 

 no doubt that it does exist. The same result was obtained in several experi- 

 ments, while horse and rabbit serum and the diphtheria antitoxin (namely, the 

 dissolved globulins) were without effect. We can not hold an unknown acci- 

 dental factor responsible for these results. 



We conclude then that Calmette's cobra antivenin has a slight neutralizing 

 action on the venom of Heloderma. The action is, however, several hundred 

 times weaker than on cobra venom. Our experiments prove, therefore, the 

 existence of a relative specificity of the snake-venom antitoxins, prepared with 



