ARTIFICIAL IMMUNIZATION 227 



Here Calmette records that the venom of Scorpio afer, 0.00005 g m - °f which 

 killed white mice in 2 hours and also a guinea-pig weighing 500 gm. in due 

 time, was neutralized by the antivenin. 0.001 gm. of the scorpion venom 

 mixed with 3 c.c. of the antivenin failed to kill guinea-pigs, though the control 

 animal died. Guinea-pigs immunized to the venom of French vipers were 

 able to resist the effects of the scorpion venom. 



Calmette inoculated a large cobra upon several occasions with 12 to 20 and 

 24 c.c. of his antivenin and found that its blood, which should have been fatal 

 for guinea-pigs in doses of 0.5 c.c, had lost all its toxicity. He thought this 

 due to neutralization of the toxic principles of the blood by the antivenin and 

 assumed that the toxicity of the blood of venomous snakes is identical with 

 that of the venom. 



In this paper Calmette further attempted to show that the immune serums 

 obtained by immunizing animals with venom and abrin are effective against 

 each other's antigen. But this statement received little experimental corrobo- 

 ration afterwards. It was about this time that the biological or cellular 

 theory of immunity of the French school was fighting hard against the chemi- 

 cal theory of the German school. Therefore, it is no wonder that Calmette 

 expressed himself in favor of the vital view of the process of passive immunity. 



Fraser 1 (1895) announced the results of his immunization experiments 

 with venom, showing that a rabbit had tolerated 50 minimal lethal doses of 

 cobra venom by means of gradually increasing doses of the venom. Then 

 his more important and extensive work 2 appeared, in which, after having 

 determined the minimal lethal dose of cobra venom for different animals and 

 that of various venoms for rabbits, he recognized the neutralizing property of 

 the serum of the immunized animal against venom, when the two are mixed 

 in vitro. The immunization was performed, for the most part, with sub- 

 cutaneous injections of venom, though he also produced immunity in cats 

 by gastric administration. Fraser gives a series of protective inoculations 

 against 1, 2, 3, and 4 lethal doses of venom: 



Series 1: One minimal lethal dose of venom, with 0.5, 0.25, 0.1, 0.05, 

 0.02, 0.01, 0.005, 0.004 c - c - of antivenomous serum respectively. 

 All these animals survived. When, however, the dose of serum was 

 reduced to less than 0.0025 c.c, they died. 



Series 2: Two minimal lethal doses of venom, with 0.75, 0.7, and 0.6 c.c. 

 of antivenin were followed by recovery, but 0.5 c.c. was insufficient 

 to effect recovery. 



Series 3: Three minimal lethal doses of venom, with 1.5, and 1 c.c. of anti- 

 venin were followed by recovery, but 0.8 c.c. did not save the animal. 



Series 4: Four minimal lethal doses of venom mixed with 2 c.c. of anti- 

 venin were followed by death. 



Fraser found that when the venom and antivenin were given in opposite 

 sides of the body, one immediately following the other, doses of 1, 2, and 3 c.c. 



1 Fraser. Trans, of the Medico-Chir. Soc. of Edinburgh, 1895, XIV, 212. 



2 Fraser. The rendering of animals immune against the venom of cobra and other serpents, and on 



the antidotal properties of the blood serum of the immunized animals. Brit. Med. Jour., 1895, 

 I. 1309- 



