CHAPTER XXV. 
INTERACTIONS BETWEEN VENOM AND ANTIVENIN. 
ESTABLISHMENT OF THE CHEMICAL NATURE OF THE VENOM-ANTIVENIN 
REACTION. 
The poisonous constituents of snake venom have one of the most important 
peculiarities of the class of substances known as toxins, namely, they stimu- 
late in the body of susceptible animals the formation of specific anti-bodies 
when introduced into the latter in sublethal quantities. ‘This was proven by 
Sewall even before the discovery of Behring and Kitasato of the antitoxin 
for diphtheria, and fully confirmed and extended by Phisalix, Bertrand, 
Calmette, Fraser, and many other later investigators. Thus the fact that 
animals immunized with snake venom acquire a higher resistance to the 
effects of the same venom, and that this acquired immunity can easily be 
transmitted to a normal animal through the introduction of the blood serum 
of the immunized animal, has been proven beyond doubt. But what is the 
cause of such protection? Is it due to the formation of new substances in 
the body of the immunized animal, capable of neutralizing the toxic substances 
of the venom, or is it due to a mere physiological tolerance of the vulnerable 
cells to the noxious effects of the poison? 
Sewall’s experiments fail to decide this point, but the work of Calmette 
and Fraser has already shown that this is not a mere toleration on the part of 
cells, but is due to the acquisition of a new property by the blood serum — 
perhaps including also certain other body fluids —as the result of artificial 
immunization, namely, the antivenomous property. In other words, the 
antitoxin has developed in the immunized animal. Thus the protection 
afforded by active as well as passive immunities is the work of antitoxin. To 
this every investigator in this field agrees. 
The next question, which has a broader bearing upon the mechanism 
of antitoxin immunity in general, is whether the counteracting property of 
antitoxin against toxin is effected directly or indirectly through the coopera- 
tion of cellular elements of the animal to be protected. 
By the first hypothesis venom is directly acted upon by the antivenin with- 
out the aid of vital process of the cells, like an acid upon a base. By the 
second hypothesis the antitoxin renders the susceptible cells less sensitive 
to the toxin without attacking the toxin directly. The former is known in 
immunity as the chemical theory, while the latter view is the cellular or vital 
theory. 
A clear-cut decision on this point has for a long time been almost impossible, 
as there were no means of separating toxin and antitoxin from the mixture of 
both, once made outside the body. All toxins and antitoxins lose their activi- 
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