72 THE PRINCIPLES OF IMMUNOLOGY 



can rattlesnake ; and the hydrophinae or poisonous sea snakes. The 

 venoms secreted by special glands are injected during the bite 

 through fine canals in the fangs (not the forked tongue), and are 

 all hemolytic. The fact that the blood of snakes contains poisons 

 similar to those of the venom indicates that the poison glands 

 secrete with little alteration the poison of the blood. Never- 

 theless, snake bites may be poisonous for snakes of other species, 

 and also for other members of the same species. Geoffroi 

 and Hunauld, in 1737, and Fontana, in 1781, noted the anticoagu- 

 lant action of venom, but the work of Weir Mitchell in 1860, 

 and of Weir Mitchell and E. T. Reichert in 1886, served as the great- 

 est stimulus to modern investigation. Mitchell and Reichert 

 showed that the venom of the rattlesnake produces rapid coagula- 

 tion of the blood and death, but that if the animal survives the blood 

 is reduced in coagulability. C. J. Martin confirmed this in regard to 

 Australian snakes and showed that the phenomenon could be con- 

 trolled by dosage of the venom. In addition to hemolysis and 

 alteration of coagulation, other properties are present, and Flexner 

 and Noguchi showed in venom the presence of hemotoxins, in- 

 cluding hemolysins and hemagglutinins, leucocytolysins, and an 

 endotheliotoxin which they named hemorrhagin. Pearce showed 

 that hemorrhagin produced lysis of endothelium leading to hemor- 

 rhage. In addition, venoms contain proteolytic enzymes, invertase, 

 lipase, and probably certain ferments dealing with coagulation. 

 Martin found fibrin ferments which probably aid in thrombus for- 

 mation. Lamb found that even citrated blood could be clotted by 

 venoms. Negrete found the anti-coagulating element closely asso- 

 ciated with the proteins of the venom. Morowitz claims the pres- 

 ence of an antithrombokinase. Modern studies by Houssay 

 Sordelli and Negrete with the venoms of fourteen snakes, Indian, 

 American, and Australian, show that clotting time does not parallel 

 closely the dose of venom, that venoms clot whole blood, plasma, 

 and fibrinogen solutions, and that mammalian blood is more sus- 

 ceptible than that of birds, batrachians, and snakes. The addition 

 of citrate, oxalate, magnesium sulphate, hirudin, and peptone delay 

 the action of the venom, the oxalate acting the most intensely. It 

 seems likely that large doses of venom bring to bear a sufficient 

 amount of fibrin ferment to produce clotting and that the later 

 effects are due to the anti-coagulating power of the venom after the 

 fibrin ferment is exhausted. Inasmuch as the hemolysis of venom 

 is somewhat closely related in mechanism to hemolysis in general, 

 it will be discussed in the chapter on Hemolysis (see page 141). 

 Venom toxins resemble other toxins in that they are precipitated 

 with proteoses, whilst the factor which produces local irritation 

 comes down with globulin, although Faust maintains that the active 

 principles of venoms are glucosides. Venom toxins are destroyed 

 by heat, the cobra poisons as a class by 100 C., and the viper 

 poisons by 85 C. They do not dialyze and deteriorate under the 



