160 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 
required respectively, 0.coor gm. of cobra, equaling 1 minimal hemorrhagic 
dose; 0.2 mg. water-moccasin, equaling 20 minimal hemorrhagic doses; 
0.6 mg. copperhead, equaling 60 minimal hemorrhagic doses; and 1 mg. 
rattlesnake venom, equaling 1,000 minimal hemorrhagic doses. 
The above estimate would amply justify the view of Flexner and Noguchi 
that the chief toxic constituent of crotalus venom resides in the hemorrhagin. 
Morgenroth has also shown that the hemorrhagin of,crotalus venom is 
extremely sensitive to the influence of acids. This investigator found that 
the inactivation of hemorrhagin can be brought about by a very weak dilu- 
tion of hydrochloric acid and its action is almost instantaneous. Even if the 
acid is injected after the venom, provided the venom was promptly followed 
by the acid injection, no hemorrhage is produced in the peritoneum of 
guinea-pigs and consequently no fatality results, even from a large quantity 
of the venom. I was able to confirm his observation to a large extent. 
Flexner and Noguchi had shown, prior to Morgenroth, that the hzmor- 
rhagin is very sensitive to acid treatment. They utilize this mode of modifi- 
cation of hemorrhagin for immunization, the disagreeable local effects having 
been easily eliminated without impairing the property of venom to produce anti- 
hemorrhagin in the immunized animals. They considered this phenomenon 
as an example of toxoid formation of hemorrhagin in Ehrlich’s sense. It is 
very interesting also to notice that a weak solution of trichloride of iodine 
produces a similar modification of the hemorrhagin and can be used for 
an easy accomplishment of crotalus immunization. Flexner and Noguchi 
have not made investigations as to the comparative merits of the unmodified 
and modified venoms in producing antivenins, but, at all events, as the degree 
of immunity reaches a certain point, the unmodified venom may gradually 
be substituted, should the modified venom prove in any respect inferior to 
the unmodified in producing strong antivenin. 
Lachesis flavoviridis s. Trimeresurus riukiuanus contains chiefly hemor- 
rhagin, while hemolysin, agglutinin, and neurotoxin are present only in 
trifling quantities. According to Ishizaka, the hemorrhagin of this venom 
becomes inactive when shaken with chloroform, or acted upon by hydrogen 
sulphite, ferric chloride, and acetic or hydrochloric acid. 
The removal of hemorrhagin by heating to 73° C. diminished its toxicity 
to one twenty-seventh, while chloroform treatment diminished it to one- 
seventeenth of its original strength. On the other hand, hemolytic and neuro- 
toxic effects are not reduced by these treatments. 
Ishizaka also found, as Flexner and Noguchi did, that tryptic digestion of 
the venom completely destroys its toxicity. The modified hemorrhagin 
(chloroform, SH,) of this venom was capable of producing anti-hemorrhagin 
in the animals by repeated injections—this confirming the toxoid formation 
of hemorrhagin first described by Flexner and Noguchi. 
The same author made an attempt to remove hemorrhagin by means of 
endothelial cells of the aorta and richly vasculated organs, but no absorption 
was observed. 
