H^MORRHAGINS OF SNAKE VENOM 157 



bility of the haemorrhagic activity in glycerin or in a dried state has also been 

 shown by this investigator. It is noteworthy that the haemorrhagic 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 haemorrhagic and the other oedematous. Usually these two effects are 

 present simultaneously and are hkely to be confused, but a closer analysis 

 seems to have revealed their independence. Thus Weir Mitchell and Reichert 

 found that the haemorrhagic e&"ects are the action of the globulins of venom, 

 but the oedematous eft"ects are produced by the dialyzable, peptone-hke, 

 proteid fractions. Cobra venom, which is very rich in the peptone-Uke pro- 

 teins, causes a marked oedema of the locahty of the bite or of the injection of 

 venom, without the characteristic haemorrhage 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 haemorrhagic principles of snake venom was, however, 

 demonstrated by Flexner and Noguchi by their biological methods. 



The venom of Crotalus adamanteus is richest in the haemorrhagic content, 

 and the removal of this principle by means of heating to 75° C. for 30 minutes 

 deprives this venom of nearly 90 per cent of its toxicity, that is to say, in 

 order to kiU an animal with the heated, haemorrhagin-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 haemorrhagic 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, haemolysins, and 

 haemagglutinins, but not hsemorrhagins, 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- 

 haemorrhagic, but not antineurotoxic, is without any protective action against 

 the neurotropic venoms, while effective against haemorrhagic venom. 



Before the studies of Flexner and Noguchi there was no distinct demarca- 

 tion drawn between the haemolytic and haemorrhagic 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 

 antihaemolytic against crotalus venom, but that having no anti-haemorrhagic 



