HiEMORRHAGINS OF SNAKE VENOM 159 



rounded and penetrated by a rich supply of blood and lymph vessels the 

 ha^morrhagin seldom invades the central nervous system in a seriously large 

 quantity. Judging from the symptoms only, v^e readily comprehend that the 

 hcemorrhagin is most energetically absorbed at the spot nearest the place of 

 venom injection. It is only vv^hen the venom enters the blood circulation that 

 danger to hfe is more apparent; otherwise one will find that hcemorrhage 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 haemorrhagin may have double func- 

 tions and that haemorrhagic 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 haemorrhagic 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, haemagglutinative, haemorrhagic, and 

 neurotoxic. By pepsin digestion we can destroy agglutinating property, 

 but haemorrhagic 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 neutrahzation 

 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 haemorrhagin, must remain unaft'ected. 



Flexner and Noguchi made a quantitative determination of haemorrhagin 

 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 haemorrhage were noted. If, as a 

 standard, i 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 haemorrhagic doses and of crotalus venom 1,000 

 minimal haemorrhagic 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 



