VENOM H/EMOLYSIS AND VENOM AGGLUTINATION 183 



Lamb also found the diminution of haemolysis with much larger doses of 



venom. 



In the meanwhile Noguchi was still pursuing his study on venom haemo- 

 lysis and tried to clear up the mechanism of lysis produced by venom in 

 the presence of certain thermostabile chemical substances other than that 

 (lecithin) discovered by Kyes. Noguchi thinks that the haemolysis caused by 

 venom can in many instances be due to the sensitizing effects of venom on the 

 haemolytic action of certain substances which are already active by themselves. 

 In other words, venom inflicts upon the blood cells certain injury and renders 

 them more vulnerable to the solvent action of these substances. Thus in 

 the case of lecithin, a typical venom activator, Noguchi points out that this 

 substance is quite haemolytic by itself. The haemolytic power of lecithin is, 

 however, about one-twentieth of what it is when used in the presence of 

 venom. This proportion is not the one which is estimated at the beginning 

 of experiments, but is obtained at the time when the reaction is almost com- 

 pleted. As was shown somewhere else, the velocity of reaction of different 

 chemicals is extremely variable according to the nature of the substance, but 

 the final sum of reaction is not parallel to the velocity of reaction. Now let 

 us take lecithin. This substance does not start to act until many hours after 

 the addition to the blood suspension, but gradually reveals its lytic property 

 in about 3 or 4 hours, and continues to be active until 18 to 24 hours. 



On the other hand, the venom lecithin haemolysis does not require a latent 

 period, but completes the reaction within half an hour or so. If a com- 

 parison of the hemolytic strength of venom lecithin and lecithin alone be 

 taken within the first 5 minutes the proportion would be no lysis with lecithin 

 against the very powerful rapid lysis of venom-lecithin mixture. If an esti- 

 mate be made after i or 2 hours it would be i to 200-300 or more in favor of 

 the latter. However, this proportion shdes gradually to the advantage of 

 lecithin, as the time requisite for its completing reaction gains, until the ratio 

 is about I to 20 after 24 hours. 



There is no question as to the formation of a definite new haemolytic com- 

 pound (lecithid) in the mixture of venom and lecithin, together with a reduced 

 incubation period of haemolysis, but it is amazing to see how rapidly this 

 reaction takes place. If a sufficiently large amount of lecithin be added, 

 haemolysis occurs instantaneously, while an insufficient amount delays the 

 process very markedly, notwithstanding the comparatively large amount of 

 venom. 



The rapidity with which lecithin haemolyzes the blood cells with the aid of 

 venom (cobra) is almost without parallel in the enzymic process — perhaps 

 with the exception of lipase upon neutral fats. Another example of a rapid 

 completion of haemolytic process is furnished by sodium oleate. This sub- 

 stance is able to haemolyze about the same amount or shghtly more of the 

 blood corpuscles as lecithin or oleic acid, but its reaction is all over within an 

 hour. In this body we see that the zymotoxic (or toxophore) group of the 

 compound is set to a rapid action through the presence of sodium. 



