290 IMMUNO-CATALYSIS 



fibrinogen. These seven venoms— Bothraps atrox, Bothrops jararaca, 

 BothrofS numndjera, Crotalus adamanteus, Crotalus terrificus terrifi- 

 cus, Crotalus terrificus hasilicus and one of three specimens of Crotalus 

 horridus were found therefore to contain a substance which, hke 

 thrombin or papain, reacted with fibrinogen to form a fibrillar gel 

 indistinguishable from fibrin. 



The clotting action of the above snake venoms was found to be 

 independent of (a) the presence of calcium, showm by the fact that it 

 occurred just as promptly in fibrinogen solutions containing sodium 

 citrate; (b) the presence of tissue or platelet derivatives, shown by its 

 occurrence in fibrinogen solutions which contained these factors only 

 in minimal concentration. The velocity of the reaction was not af- 

 fected at all by the addition of cephalin or tissue extracts to the 

 fibrinogen; (c) the presence of prothrombin, for the prothrombin-free 

 fibrinogen which was unaffected by Ca+cephalin, was nevertheless 

 clotted by the venoms. These facts showed that the formation 

 of fibrin was catalyzed directly by the snake venom. The eleven ven- 

 oms which did not clot fibrinogen were found to hydrolyze protein and 

 render it indifferent to thrombin. 



The venoms arranged in order of their gelatin-splitting activity 

 showed also proportional clot-forming activity. When the proteolytic 

 activity of certain venoms was found to be below a certain level they 

 also failed to manifest any effect on fibrinogen. On the other hand, 

 some of the venoms which manifested a high degree of proteolytic 

 activity rendered the fibrinogen indiflferent even to thrombin. 



c. The Activation of Prothrombin to Thrombin by Snake 

 Venoms. Three of the 17 venoms— Notec/iis sentatus, Bothraps atrox, 

 Bothrops jararaca— used in dilutions as high as 1 : 1 ,000,000 (the first 

 two named in 1:10,000,000 dilutions), regularly catalyzed the trans- 

 formation of prothrombin to thrombin. The mixed venoms of Micrurus 

 and Crotalus terrificus hasilicus were found to be weakly active. 

 Notechis scutatus and a mixed Micrurus venom did not show any 

 effect on fibrinogen; their activity on plasma noted previously was 

 ascribed to their property of transforming prothrombin to thrombin. 

 The other three venoms activated prothrombin and acted also on 

 fibrinogen. 



Despite the fact that these venoms represent a heterogeneous mix- 

 ture of substances, the first 3 were found to be many times as effective 



