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 hemolysins of the crotalus as well as the 
cobra venom had also undergone a considerable diminution during this period. 
In testing the hemorrhagic activity of crotalus venom, it was quickly found 
that the content in hemorrhagin was undiminished. In other words, the 
hemorrhagins 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 hemorrhagins and the general toxicity in con- 
tradistinction to the other toxic principles is clearly demonstrated. 
Flexner and Noguchi also demonstrated that the hemorrhagins 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 4oo grams of body-weight, o.cor gm. of crotalus venom, given subcutane- 
ously, kills in about 3 hours, while a smaller dose than this produces extensive 
swelling, hemorrhage, and sloughing, but not death. With the same sample 
of the venom, 0.00005 gm. 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 hemorrhagin, 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- 
