ANTI-ENZYME IMMUNITY 289 



4. Antibody Against the Plasma Clotting Enzymes of 

 Snake Venom 



a. Enzymic Nature of Blood Clotting Activity of Snake Venoms. 



Schmidt (1892, 1895), one of the earliest men to work on the plasma- 

 clotting problem, termed thrombin a fibrin-ferment. 



Eagle studied (1937, 1939) several snake venoms with regard to 

 their blood clotting properties. Certain venoms were shown to inhibit 

 the clotting process when added to blood in vivo and in vitro, a few had 

 no significant effect, and a large number exercised marked clotting 

 action on whole blood, plasma, or fibrinogen. 



Trypsin, like Ca-platelets (or Ca-tissue), catalyzes the transforma- 

 tion of prothrombin to thrombin, and papain, like thrombin, catalyzes 

 the transformation of fibrinogen to fibrin. Eagle investigated the 

 question as to whether the clotting action of snake venoms depends 

 on their enzyme content, and whether these venoms are of two types. 

 The question formulated by him was as follows : 



(a) Is there one type which, like trypsin and like the Ca-platelet 

 system, acts on prothrombin to form thrombin; and 



(b) another which, like papain and thrombin, acts directly on 

 fibrinogen to form fibrin. The experimental data supported his assump- 

 tions. 



Fibrinogen. The purified fibrinogen used in these experiments did 

 not clot on the addition of calcium and lung extract, but promptly 

 formed clot by thrombin. 



Prothromhin. The crude prothrombin preparation was freed from 

 fibrinogen. The isotonic solution of prothrombin preparation rapidly 

 evolved thrombin in large amounts on the addition of 0.5 volume of 

 1 per cent calcium chloride and cephalin (or lung extract). The addi- 

 tion of calcium alone had either no demonstrable effect, or caused a 

 very slow elaboration of minute quantities of thrombin, less than 2 

 per cent of the amount elaborated from the same prothrombin in the 

 presence of an adequate amount of cephalin or tissue derivatives. 



b. The Clotting of Fibrinogen by Snake Venoms. Eight of the 

 seventeen venoms tested exercised active clotting effects, and one 

 (_Crotalus horridus') yielded variable results. 



Seven of the nine venoms which clotted plasma also clotted purified 



