ARTIFICIAL IMMUNIZATION 225 



Phisalix * altered the venom of viper by alternating currents of high fre- 

 quency and found the modified venom to act as a protective vaccine. 



Phisalix and Bertrand next succeeded in separating the toxic and the 

 immunizing principles of the venom of viper by passing a i : 5,000 solution 

 through the porcelain filter. Toxicity was almost completely absent from 

 the filtrate, but the echidno-vaccine was still contained in it, as the injec- 

 tion of the filtrate into guinea-pigs rendered the animals refractory to 

 the effects of two minimal lethal doses of fresh unfiltered venom given 48 

 hours later. 



Calmette,^ later, dissented from the above statement, as he found that 

 filtration simply reduced the toxicity of venom to two-fifths of its original 

 power, but if proteins were removed by heat-coagulation before the filtration, 

 practically all passed through. The vaccination reported by Phisalix and 

 Bertrand he looks upon as merely an early stage of the usual form of experi- 

 mental immunity. 



PASSIVE IMMUNITY — ANTIVENINS. 



Since the successful therapeutic apphcation of the diphtheria antitoxin the 

 future of the problem of immunity has assumed quite a new aspect. The 

 discovery of Behring and Kitasato, that the protective principle developed 

 in the animal successfully immunized against a particular toxin can be trans- 

 mitted into a normal animal and confer upon the latter the power to resist 

 the otherwise lethal action of the toxin in question has now been brought 

 into the study of venom immunity. Naturally the basis of such possibihty 

 in venom is dependent on whether or not the animals can be made actively 

 immune by the sublethal inoculation of venom. This has been established 

 affirmatively by Sewall, Kaufmann, Phisahx, and Bertrand in their pre- 

 ventive inoculation, either with unmodified or heated venoms. 



The first observation upon the antitoxic property of the blood of animals 

 immunized to venom was made by Phisalix and Bertrand.^ They found 

 that when guinea-pigs were killed 48 hours after vaccination with the echidno- 

 vaccine, their serum or dcfibrinated blood mixed with the venom and injected 

 into the peritoneal cavity of other guinea-pigs enabled them perfectly to resist 

 the action of the venom. 



In the meanwhile Calmette commenced to install the results of his famous 

 series of studies bearing on the production of antivenin, with such progress 

 that he finally succeeded in introducing the antivenin to preventive and 

 therapeutic apphcations in the treatment of snake bite. He^ first employed 

 the usual laboratory animals, such as rabbits and guinea-pigs, to immunize 

 with cobra venom. 



1 Phisalix. Attenuation du venin de vipere par les courants a haute frequence; nouvelle methode de 



vaccination contre le venin. Compt. rend. d. 1. Soc. d. Biol., 1896, 10 serie, III, 233. 

 ' Calmette. Serpents' venom and antivenomous serum. Brit. Med. Jour., 1896, II, 1025. 



* Phisalix and Bertrand. Sur la propriete antitoxique du sang des animaux vaccines contre le venin 



de vipfere. Compt. rend. d. I'Acad. d. Sci., Paris, 1894, CXVIII, 356. 



* Calmette. L'immunisation artificielle des animaux contre le venin des serpents, et la th6rapeutique 



experimentale des morsures venimeuses. Compt. rend. d. 1. Soc. d. Biol., 1894, 10 serie, I, 120. 



