6 THE VENOM OF HELODERMA. 



The discovery of Neuberg that a certain parallelism exists between the 

 hemolytic power of certain toxic substances and their contents in lipase sug- 

 gested the responsibility of the lipase for the hemolytic effect. It was therefore 

 of interest to compare the heat-resistance of the lipolytic and hemolytic sub- 

 stances in heloderma venom. After heating it to 60 C. for 30 minutes, its 

 hemolytic power is not impaired. No appreciable loss is noticeable after heat- 

 ing it 10 minutes to 100 C. After heating it to 100 C. for 30 minutes a great 

 part of its hemolytic power is lost, and after exposing it to a temperature of 

 120 C. for 15 minutes in the autoclave it has lost all of its hemolytic power. 

 According to Alsberg, lipase of heloderma venom is weakened after heating to 

 00 C. during 30 minutes; it is destroyed after an exposure to 100 C. lasting 

 10 minutes. The lipolytic power of venom is therefore distinctly less heat- 

 resistant than its hemolytic power; the venom is still hemolytic after its 

 lipase has been destroyed through heating. We may therefore conclude that 

 lipase and hemolytic principle are not identical in the venom of Heloderma and 

 probably not in snake venoms. Of course the possibility exists that after all 

 lipase and hemolytic principle have some components in common. 



We are not in a position to state definitely through what mechanism the 

 venom of Heloderma causes hemolysis. Certain facts suggest, however, that 

 lecithin and venom may increase the permeability of the erythrocytes. In the 

 case of cobra venom von Dungern and Coca and also Manwaring believed that 

 the venom splits the lecithin and that a splitting of lecithin is the real hemo- 

 lytic agent. In the case of heloderma venom we saw that the amounts of 

 venom and of lecithin required for hemolysis stood in inverse ratio. 



It seems to me that two facts indicate that the venom-lecithin mixture 

 increases the permeability of the erythrocytes. In the first place, I would thus 

 interpret the observations of Bang and Overton, who found that the action in 

 vitro of cobra or crotalus venom upon tadpoles is counteracted by addition of 

 CaCl 2 . Now, according to Jacques Loeb and W. J. V. Osterhout (Science, 

 Dec. 15, 1911, Jan. 19, 1912), CaCl 2 inhibits the entrance into the cells of vari- 

 ous salts of monovalent atoms. We may assume that it acts in a similar 

 manner in combination with venom, but in other cases CaCl2 may produce its 

 inhibiting influence by inactivating soaps, as has been previously pointed out 

 by Noguchi. In a similar manner I would interpret the observation of Goebel. 

 According to him, corpuscles suspended in 0.85 per cent NaCl solution, which 

 can not be hemolyzed by cobra venom alone, are hemolyzed if the latter are 

 suspended in isotonic solutions of saccharose. It seems to me that this fact is 

 similar to the results which I obtained in the course of my investigations into 

 the influence of external conditions upon the blood-cells of Limulus (Folia 

 Hsemotologica, Bd. 4, 1907; Pfliiger's Archiv, 1910, Bd. 131). In this case I 

 have shown that solutions of non-electrolytes behave somewhat similarly to 

 H 2 and produce similar lytic changes. We should therefore expect that cor- 

 respondingly they are also more favorable to hemolysis than are salt solutions. 



It would be of interest to study thoroughly the various factors in their 

 relation to hemolysis which 1 investigated previously in their significance for 



