NEUROTOXINS OF SNAKE VENOM 149 



Calmette and Massol * confirmed the finding of Morgenroth that the neuro- 

 toxin can be separated from the neutral mixture of venom and antivenin 

 by means of a weak solution of hydrochloric acid and by almost any acid, 

 mineral or organic. More striking is their finding that the neurotoxic principle 

 of cobra venom can be extracted from the mixture of venom and antivenin by 

 means of 50 per cent alcohol, in which antivenin is insoluble. In fact, Cal- 

 mette and Massol found that the neurotoxin can be extracted from venom 

 solution by alcohol as high as 86 per cent. They employed findings to show 

 the reversible nature of the compound of venom and antivenin, and I shall 

 later return to this subject in a proper place, when discussing the properties 

 of antivenin. 



The neurotoxic principles of snake venom possess specific afhnity toward 

 the nerve tissues. Flexner and Noguchi showed that if a few minimal lethal 

 doses of ancistrodon venom be mixed with the mashed brain-substance of 

 susceptible animals the greater portion of the toxicity disappears from the 

 fiuid obtained by centrifugahzation of such mixture. This fixation of the 

 neurotoxic principles is very pronounced when the emulsion of brain sub- 

 stances is employed, but none or only slightly when the emulsions of other 

 organs are used. Myers, who made a similar experiment before these 

 authors, failed to obtain a positive result. 



Calmette lately also found that there is absorption of toxic principles of 

 cobra venom by the brain emulsion. 



After the work of Kyes cholesterin is known to possess a certain antihaemo- 

 lytic property against native cobra venom or lecithid, and the isolation by 

 Faust of a sapotoxin from the cobra venom, and the discovery by Ransom of 

 the antisaponic property of cholesterin, the phenomenon of Flexner and 

 Noguchi, the fixation of the neurotoxin by the nerve tissue, may have to be 

 viewed in a different light. It remains to be seen whether the ophiotoxin of 

 Faust is neutralized by cholesterin or not. In the case of positive outcome, 

 the phenomenon of fixation may simply be due to the action of cholesterin in 

 the brain emulsion. The fixation of tetanus toxin by the brain emulsion, as 

 discovered by Wassermann and Takaki, is no longer a specific phenomenon, 

 but is considered to-day to be the action of cholesterin, protagon, cerebrin, 

 etc. In this regard Noguchi demonstrated that tetanolysin is neutralized by 

 cholesterin, while Landsteiner showed that tetanus toxin is inactivated by 

 protagon. Again, it may be recalled here that Fraser discovered long ago 

 that the bile has antivenomous property against cobra venom. 



One of the most important and interesting questions concerning the neuro- 

 toxins of snake venoms, both from the practical and the theoretical points 

 of view, is the identity of these principles. It is no wonder that none of 

 the earlier investigators raised this question, because symptomatology does 

 not reveal such delicate differences. All investigations of pre-antitoxin age 

 passed it as granted that the neurotoxic effects of various venoms are pro- 



1 Calmette and Massol. Relations entre le venin de cobra et son antitoxine. Ann. Inst. Pasteur, 1907, 

 XXI, 939. 



