VENOM HEMOLYSIS AND VENOM AGGLUTINATION 169 



combining property of varying affinity. With this assumption Myers explained 

 these results, and thought that cobra venom contains, besides real intact 

 hsemolysin, a number of toxoids, which are still able to unite with the anti- 

 toxin, although their haemotoxophore side-chains are inert. In some instances 

 he found that the first fraction of the serum neutralized somewhat less than 

 the second. In these cases the presence of prototoxoids was assumed. In 

 fact, according to this hypothesis, the neutralization of a given amount of 

 cobralysin means the neutralization of toxin and toxoids (prototoxoid and 

 deutotoxoid, but not the least reactive epitoxoid) ; and the amount of any one 

 fraction of the antivenin to combine is always the same (only differing in the 

 toxic expression) , which is due to the toxin alone, but not to the toxically inert, 

 antivenin-combining toxoids. At last, Myers tried to determine the reason 

 for the fact that in a venom there can be present toxin and toxoids. He found 

 that when a solution of cobra venom is placed at room temperature (still 

 quicker at 37 C.) its hemolytic power becomes rapidly reduced. This 

 reduction in haemolytic power was not followed by a parallel loss of its com- 

 bining power with antivenin. In other words, haemolytic toxoids were formed 

 in such solutions. 



THE NEW ERA OF THE STUDY OF VENOM HAEMOLYSIS. 



Definite proofs of the existence of hsemolytic and hasmagglutinative sub- 

 stances in different venoms in varying proportions have thus been amply 

 brought about both in corpore and in vitro. In the last few years prior to 

 1900, the investigations assumed a character of quantitative estimation of 

 the haemolytic principles in various venoms and suggested their specificity 

 as well as their insignificance in the lethal properties of these venoms. The 

 estimate made of their action upon the blood corpuscles was, however, not 

 understood at all. It was Flexner and Noguchi who for the first time found 

 that the active principles of the venom require a second substance to mani- 

 fest their solvent function upon the blood corpuscles, and this marks the 

 opening of the new era of study of the hsematoxic actions of the venom. 



In 1902 these investigators discovered that certain venoms do not dissolve 

 the blood corpuscles from which every trace of serum has previously been 

 removed by repeated washings in an isotonic saline solution. But if the 

 separated serum is restored to each of the several kinds of blood corpuscles 

 treated with venom, lysis takes place. They found that the substance or 

 substances of those serums capable of activating the haemotropic principles 

 of venom have the properties of serum complements, inasmuch as the elective 

 removal of the serum-amboceptors for each kind of the washed corpuscles 

 by absorption in the cold (o° C.) did not impair their activating property, 

 and heating the serum to 56° C. for 30 minutes deprived some of the serums 

 of this activating action. Neither did solution of the venomized corpuscles 

 take place at o° C. The abolition of the activating property by heating to 

 56 C. was observed with the serums of rabbits, guinea-pigs, and Necturus, 

 but seldom with that of dogs. The velocity of the hsemolytic process was 



