HA MORRHAGINS OF SNAKE VENOM 159 
rounded and penetrated by a rich supply of blood and lymph vessels the 
hemorrhagin seldom invades the central nervous system in a seriously large 
quantity. Judging from the symptoms only, we readily comprehend that the 
hemorrhagin is most energetically absorbed at the spot nearest the place of 
venom injection. It is only when the venom enters the blood circulation that 
danger to life is more apparent; otherwise one will find that hemorrhage will 
gradually extend wider and wider, but with gradual diminution in its severity, 
to the remote parts of the body. Naturally a certain portion of the venom 
necessarily enters the circulation and finally reaches the vitally important 
region of the brain, and death may follow even the subcutaneous injections, 
but only after the application of a comparatively large dose. 
It is certainly not denied that venom hemorrhagin may have double func- 
tions and that hemorrhagic effects are only one of the two or more properties 
it possesses; it may attack certain constituents of the central nervous system 
as well, but, if it has such action at all, it must be altogether different from 
that of other neurotropic toxins of venom in general, because its symptoms 
are entirely different. Moreover, the hemorrhagic and neurotoxic effects — 
assuming their existence — are produced by the same fraction and disappear 
at the same time; these are inseparable by our present methods. 
In this connection reference may be made to ricin. As is well known, this 
phytotoxin possesses three functions, hemagglutinative, hemorrhagic, and 
neurotoxic. By pepsin digestion we can destroy agglutinating property, 
but hemorrhagic and neurotoxic effects still persist. At present we can not 
separate the two effects as the work of two distinct substances. Antiricin 
can neutralize all three properties. It may be that these effects are due to 
the actions of their correspondingly active principles, and the neutralization 
by the antiricin is due to the presence of three distinct anti-bodies in the latter. 
On the other hand, as the antiserum produced with the non-agglutinating 
digested ricin is able to neutralize the agglutinating function of unmodified 
ricin, it is not at all improbable that the toxic molecule of the ricin has three 
different toxophore groups and one common haptophore group; hence the 
neutralization by antiricin is to combine with and render the common hap- 
tophore group inactive. We therefore may consider this point still open to 
investigation. At all events, Flexner and Noguchi’s view, ascribing the chief 
toxic principle of crotalus venom to hemorrhagin, must remain unaffected. 
Flexner and Noguchi made a quantitative determination of hemorrhagin 
in various venoms. For this purpose intraperitoneal injections of venom were 
employed in guinea-pigs. The lethal dose having been left out of considera- 
tion and the animals which survived having been etherized 30 minutes after 
the inoculation, the existence and degree of hemorrhage were noted. If, as a 
standard, 1 mg. of cobra venom is taken as representing 10 minimal hemor- 
rhagic doses, the same quantities of water-moccasin and copperhead venom 
would contain 100 minimal hemorrhagic doses and of crotalus venom 1,000 
minimal hemorrhagic doses. If the quantity of venom necessary to cause 
death in a guinea-pig, weighing 300 grams, in 4 hours is injected, there will be 
