196 THE VENOM OF HELODERMA. 



from the viper into guinea-pigs. All these guinea-pigs survived, while all the 

 control animals injected with the blood of normal vipers died. The toxicity of 

 the blood is destroyed by heating it to 68° C, but if the heated blood is injected 

 into guinea-pigs it confers an increased resistance to venom. 



Calmette (18) also observed this and called attention to the fact that while 

 the toxicity of blood was lost at 68° C, the venom would resist prolonged heat- 

 ing at much higher temperatures. He concludes that the toxic substance is 

 probably not venom but a diastatic substance, physiologicallj- distinct, but 

 analogous to some constituent of the venom. It may be a forerunner from 

 which the venom is produced in the process of secretion bj- the poison gland. 



Flexner and Noguchi (19, 20) made no definite statement concerning this 

 fact, but distinguished between the two sets of active principles by their capa- 

 bility to unite with or be activated by their homologous and heterogeneous 

 complements. 



Fraser (21) thinks the immunity depends on changes, similar to artificial 

 immunization, produced in the serum by constant absorption of venom, which 

 all snakes secrete in varying amounts. Tlie venom may enter the body through 

 abrasions, through the mucous membrane of the alimentary tract, or maj^ be 

 absorbed directly from the venom gland by its lymph channels. The animal 

 (4) may also receive venom from its own bite or the bite of other animals. In 

 the artificially immunized animal, definitelj- antitoxic substances may be dem- 

 onstrated by the usual methods. Metschnikoff (22), by mixing the blood- 

 serum and venom of a scorpion, showed an undoubted neutralizing power in the 

 blood. 



Fraser (2) found that the serum of a Hamadryas destroyed the toxic action 

 of cobra venom; this power was present both when the blood-serum and ^•enom 

 were injccterl simultaneously or at intervals of 15 or 30 minutes. This fact 

 also he found was true of tlie blood serum of the Australian blacksnake and the 

 venom of the same snake. His experiments show that definite substances are 

 present in the serum of poisonous snakes antidotal against their own or alien 

 venom. Natural antidotal substances are, however, not as strong as those 

 found in the blood of animals immunized against venom. 



In the case of the Heloderma sitspedum, Cooke and Loeb showed that 

 while the monster possessed an immunity against its venom, its blood was not 

 toxic, nor did it possess antidotal properties. Notwithstanding this deficiency 

 in demonstrable antitoxin the serum might perhaps contain certain antibodies 

 which could be demonstrated by the complement fixation test of Bordet and 

 Gengou (23), especially inasmuch as Cooke and Loeb (8) have shown that the 

 venom contains an antigen which on injection into rabbits causes the formation 

 of precipitins. 



Two series of experiments were made to test for the presence of antibodies 

 in the blood-seriun or the power of the mixture of serum and venom to fix com- 

 plement. In one, the active and the inactive serum of the Heloderma was used 

 with an antihuman hemolytic system and in the other inactive serum and an 

 antisheep system. 



