HA MORRHAGINS OF SNAKE VENOM 157 
bility of the hemorrhagic activity in glycerin or in a dried state has also been 
shown by this investigator. It is noteworthy that the hemorrhagic activity of 
various venoms is parallel with the amount of globulin-like bodies in these 
venoms. 
One can distinguish two distinct local effects produced by various venoms, 
one hemorrhagic and the other oedematous. Usually these two effects are 
- present simultaneously and are likely to be confused, but a closer analysis 
seems to have revealed their independence. Thus Weir Mitchell and Reichert 
found that the hemorrhagic effects are the action of the globulins of venom, 
but the oedematous effects are produced by the dialyzable, peptone-like, 
proteid fractions. Cobra venom, which is very rich in the peptone-like pro- 
teins, causes a marked cedema of the locality of the bite or of the injection of 
venom, without the characteristic hemorrhage in the same degree as in the 
case of viperine or crotaline poisoning. (Plate 26.) 
That the venom of vipers is much the same in its general effects as the 
crotaline venom is recognized by all investigators from the time of Fontana, 
Mitchell, Fayrer, and Brunton, and for the purpose of avoiding severe local 
reactions during immunization of animals Calmette employed various chemical 
and physical agents to eliminate this principle. The clearer and more defi- 
nite analysis of the hemorrhagic principles of snake venom was, however, 
demonstrated by Flexner and Noguchi by their biological methods. 
The venom of Crotalus adamanteus is richest in the hemorrhagic content, 
and the removal of this principle by means of heating to 75° C. for 30 minutes 
deprives this venom of nearly go per cent of its toxicity, that is to say, in 
order to kill an animal with the heated, hemorrhagin-free venom 10 to 20 
times the minimal lethal dose of the original, unheated venom is required, 
and the cause of death in the case of the heated crotalus venom is chiefly due 
to the presence of the thermostabile toxic principle of neurotropic nature. 
Again, the removal of the neurotoxic principle by means of brain emulsion, 
which is capable of fixing the neurotropic principle of various venoms, does 
not materially alter the hemorrhagic content, and at the same time no diminu- 
tion in the general toxicity of the crotalus venom takes place. Antivenin 
which is able to neutralize a large amount of neurotoxins, hemolysins, and 
hemagglutinins, but not hemorrhagins, is only effective against the fatal 
effects of certain neurotropic venoms, such as cobra or some ancistrodon 
venoms, but proves to be totally ineffective against the fatal action of crotalus 
venom. Inversely, it was found that the antivenin which is strongly anti- 
hemorrhagic, but not antineurotoxic, is without any protective action against 
the neurotropic venoms, while effective against hemorrhagic venom. 
Before the studies of Flexner and Noguchi there was no distinct demarca- 
tion drawn between the hemolytic and hemorrhagic processes, and they were 
described in confusion. But these investigators, by various means, soon 
cleared away the doubts surrounding the case. On one occasion they found 
that the antiserum from animals immunized with crotalus serum is markedly 
antihemolytic against crotalus venom, but that having no anti-hemorrhagic 
