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- 

 ical 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 1895 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 5 to 10 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 the chemical nature of the reaction. He denies the 

 probabihty 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 D^larde ^ 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 



» Calmette. Contribution a I'etude des venins. Ann. Inst. Pasteur, 1895, IX, 225. 

 2 Fraser. The limitation of the antidotal power of antivenene. Brit. Med. Jour., 1896, II, 910. 

 2 Calmette and Delarde. Sur les toxins non-microbines et le mecanisme de I'immunite par les serums 

 antitoxiques. Ann. Inst. Pasteur, 1896, X, 675. 



