158 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 



property it failed to counteract the fatal effects of the venom in vivo. In 

 another instance they found that crotalus venom solution remained almost 

 unaltered in its general toxicity after being kept at 70 C. for a period of 

 8 weeks, while that of Cobra had undergone a deterioration down to one- 

 tenth of the original activity. The haemolysins of the crotalus as well as the 

 cobra venom had also undergone a considerable diminution during this period. 

 In testing the haemorrhagic activity of crotalus venom, it was quickly found 

 that the content in haemorrhagin was undiminished. In other words, the 

 haemorrhagins of crotalus venom are remarkably stable in this particular 

 respect, although against high temperature, acids, and other chemical pro- 

 cesses, such as oxidation, they are more sensitive to inactive modification. 

 Here the persistence of the haemorrhagins and the general toxicity in con- 

 tradistinction to the other toxic principles is clearly demonstrated. 



Flexner and Noguchi also demonstrated that the haemorrhagins of crotalus 

 venom constitute the chief toxic constituents of this venom, by showing the 

 difference which arises from the different modes of introduction into the 

 body. With the neurotropic venoms it matters but little in the final issue 

 whether they are injected into the blood circulation, into the muscular sub- 

 stances, into the serous cavities, or under the skin. Usually death follows 

 more quickly when the venom reaches the central nervous system according 

 to the mode of administration, while the minimal lethal dose remains the 

 same or not very different. On the other hand, if the crotalus venom is 

 injected directly into the brain substance or into the cranial cavity, death is 

 brought about by a small fraction of the minimal lethal dose that is esti- 

 mated by the subcutaneous administration of the venom. Taking guinea-pigs 

 of 400 grams of body- weight, o.ooi gm. of crotalus venom, given subcutane- 

 ously, kills in about 3 hours, while a smaller dose than this produces extensive 

 swelling, hasmorrhage, and sloughing, but not death. With the same sample 

 of the venom, 0.00005 S m - suffices to kill the animals in about 3 hours when 

 injected into the brain. Thus the direct application of crotalus venom to the 

 brain is about 20 times more poisonous than that administered under the skin. 



The above experiments clearly point out the difference in the modes of 

 producing fatal effects by cobra venom on one hand and by crotalus venom 

 on the other. Flexner and Noguchi explain this difference on the ground 

 that the neurotoxin, the chief toxic principle of cobra venom, has a specific 

 affinity to the nervous tissue, namely, the ganglion cells of certain parts of 

 the central nervous system, and is not much absorbed or fixed by the other 

 tissues; hence its final effects are nearly the same, irrespective of the mode of 

 injection, although more time is required for the subcutaneous injections 

 than for the intravenous or intracranial administrations. On the other 

 hand, the haemorrhagin, the chief toxic principle of crotalus venom, has a 

 specific affinity to the endothelial cells composing the wall of the blood and 

 lymph vessels, and when it is introduced at a remote part from the vitally 

 important organ, namely, the brain, it has to travel to the latter in order to 

 produce fatal effects, but as the entire system of the living body is sur- 



