ANTI-ENZYME IMMUNITY 291 



in this respect as crystalline trypsin. A 1:2,000,000 dilution of Bo- 

 throfs atrox often produced a complete activation of prothrombin to 

 thrombin; and 1:25,000,000 dilution manifested a definite, if partial 

 effect. The reacting proportions therefore varied from 1 : 1 000 and 

 1 : 10,000, which can be interpreted as evidence of a catalytic process 

 and different from simple chemical combination. 



As with trypsin, the transformation of prothrombin with snake 

 venoms was independent of calcium ion, platelets or tissue derivative 

 (cephalin). Moreover the rate of transformation and the amount 

 of thrombin formed were not affected by the addition of these 

 factors. 



From the above discussion it is apparent that the clot-forming 

 agents in snake venoms act in a manner comparable to enzymes. The 

 question as to what degree these enzymes contribute to the patho- 

 logical symptomology arising from snake poisoning and what is the 

 direct bearing of the neutralizing property of antivenom immune 

 sera on the anti-enzyme immunity will be taken up next. 



d. Anti-Thrombin, Anti-Proteolytic, and Anti-Necrotic Activities 

 of Antivenin. In a meeting of the British Medical Society, Stephens 

 and Myers (1898) discussed a demonstration held in 1896 in the Phys- 

 iological Society by Professor Kanthack showing that cobra venom 

 mixed with shed blood in a test tube prevented fibrin formation; he also 

 showed that this action could be prevented by previously mixing the 

 poison with antivenomous serum— the mixture clotting as normal 

 blood did; and finally he showed that the action of the serum was 

 specific. This appears to be an early observation on the proteolytic 

 activity of snake venom and its neutralization by antivenomous 

 serum. According to Vellard (1930) the neurotoxic, clot-forming, and 

 proteolytic properties of snake venoms are the most important from 

 the point of view of toxicity. In vivo, while the clot-forming activity of 

 venom causes more or less extensive intravascular thrombosis, the 

 proteolytic activity of venoms may render the serum difficult to clot, 

 maintaining the blood in the vessels in fluid form for a long time even 

 after death has occurred. Autopsies of the animals confirmed the in 

 vitro studies. The local necrotic action of certain venoms is due 

 principally to their clot-forming and proteolytic properties; one can 

 study this effect satisfactorily in vivo by intra-dermal injection in the 

 ear of a rabbit of a sublethal dose of venom. In vitro experiments show 



