INTERACTIONS BETWEEN VENOM AND ANTIVENIN 247 
ties at about the same degree of temperature, both being destroyed some- 
where about 75°C. or even lower. Separation through filtration is equally 
unavailable, as they appear to have about the same molecular size. Chem- 
‘cal destruction of one or the other has so far been unsuccessful, both being 
easily inactivated by such treatment. Notwithstanding all these difficulties, 
Ehrlich, Behring, Kitasato, Madsen, and others have held the chemical theory, 
while Metchnikoff and Roux and their adherents have maintained the vital 
theory. It is therefore quite natural that the vital theory has shown a marked 
tendency to disprove the specific nature of an antitoxin, inasmuch as diverse 
reagents may eventually produce similar effects upon the cells and raise their 
resistance to a certain toxin or infectious virus. On the other hand, the 
chemical theory has been restricted to the phenomena concerning toxins and 
antitoxins, but not the form-elements like bacterial infection in the narrow 
sense, and hence to a more strict specificity of the reaction. 
To decide the mechanism of toxin-antitoxin reaction Calmette drew the 
reaction between venom and antivenin into the discussion. Venom offers a 
great advantage over the more labile toxins for settling this dispute, because 
its toxic principles are remarkably resistant both to high temperature and to 
many chemical reagents, by which antivenin is easily destroyed or inactivated. 
In 189s Calmette * demonstrated that in the mixture of venom and antivenin 
the former remains unaffected by the latter and both are present side by side. 
Mixtures of venom and antivenin were so prepared as to be neutral or harm- 
less for rabbits. Part of the mixture was at once injected into an animal and 
did no harm. The other portion was heated to 68° C., by which the anti- 
venomous serum was destroyed by coagulation, then injected into a rabbit, 
which died. From this experiment it is concluded that the antivenin does 
not destroy the venom in vitro, as the heat, which affects the serum but not 
the venom, was able to effect the separation of the two, which it could scarcely 
have done had the reaction been chemical. 
Fraser? then showed that when 1.3 c.c. of his antivenin per kilo is mixed 
in vitro with 5 minimal lethal doses of cobra venom and the mixture allowed 
to stand s to ro minutes, death follows its injection into animals, though when 
the mixture is allowed to stand 20 minutes or longer the animal recovers. 
This he thinks proves thé chemical nature of the reaction. He denies the 
probability that leucocytes are active in protecting the venomized body 
against the poison, being stimulated by the antivenin, and he concludes that 
the theory of vital stimulation is equally untenable. 
Calmette and Délarde® insisted upon the vital process of immunity and 
refused to accept the chemical explanation. They quote some instances 
where the antitoxin function does not exist in spite of a high degree of acquired 
immunity against certain toxins. Certain immune serums exert non-specific 
ee eee eee ee 
1Calmette. Contribution a l’étude des venins. Ann. Inst. Pasteur, 1895, IX, 225. 
2Fraser. The limitation of the antidotal power of antivenene. Brit. Mea Jour., 1896, II, gro. 
3 Calmette and Delarde. Sur les toxins non-microbines et le mécanisme de l’immunité par les sérums 
antitoxiques. Ann. Inst. Pasteur, 1896, X, 675. 
