8 THE VENOM OF HELODERMA. 



Correspondingly, invertebrates also show no or only very slight susceptibility 

 to cobra venom. As we mentioned above, echinoderm eggs, although not 

 affected by heloderma venom, are affected by cobra venom. The similarity in 

 the lethal dose of heloderma venom pro kilo animal which we found in the case 

 of most mammalians tested is surprising indeed if we consider that a number 

 of variable factors determining the lethal dose comes into play, and that these 

 factors might be expected to vary in the case of different species. Further- 

 more, we have to consider the difference in size and number of nerve-cells in 

 various species. It appears doubtful what we really measure in determining 

 the lethal dose. Is it the amount of venom entering each ganglia-cell of the 

 respiratory center? The fact that notwithstanding these complications a great 

 similarity exists in the lethal dose pro kilo animal indicates that the amount of 

 venom absorbed and reaching the respective ganglia-cells must be very similar 

 in different species. In the case of the white rat, is the respiratory ganglia-cell 

 less sensitive, or does less venom get into contact with each ganglia-cell, or 

 are the ganglia-cells less permeable? These questions we can not answer at 

 present. As in the case of other poisonous animals, we found Heloderma to be 

 immune against very large doses of its own venom when injected subcutane- 

 ously. Whether they are susceptible to an intracerebral injection of venom, 

 as (according to Phisalix) snakes are in the case of their own venoms, we have 

 not had an opportunity to investigate. 



In this connection an observation of A. Fluhner (Archiv f. Exp. Path., 

 1910, 63) is of special interest. This author found that the heart of toads is 

 not immune against the venom of Bufo, which is principally a heart-poison. 

 Natural immunity of a species against its own venom here, as well as in the 

 case of snakes, is therefore not dependent upon a lack of susceptibility to the 

 poison on the part of those cells upon which the toxic substance principally 

 acts. We might here also recall the fact that the erythrocytes of Heloderma 

 are not immune against the hemolytic action of the venom of this animal. 

 We may therefore conclude that the natural immunity is based on other fac- 

 tors. Secondary mechanisms evidently exist which protect the sensitive cells 

 against the action of the poison. 



Phisalix believed that the natural immunity of poisonous animals against 

 their own venom depends upon the presence of antitoxin in the circulation. 

 In the case of Heloderma such antitoxic substances certainly do not exist, not 

 even in animals whose poison gland had been removed some time previously, 

 in order to obviate a neutralization of antitoxin which might be present by the 

 venom discharged into the blood through a process of internal secretion. There 

 exists, however, another mechanism through which a natural immunity could 

 be obtained. Should some provision in other organs prevent the venom from 

 reaching the brain and acting upon the nerve-cells, the latter would be pro- 

 tected against the injurious effect of the venom. Such an explanation of natural 

 immunity was suggested by Wolff-Eisner several years ago. It seemed, there- 

 fore, worth while to compare the absorptive action of the pulp of various organs 

 for the venom of Heloderma, and furthermore to make a comparative test of 



