ARTIFICIAL IMMUNIZATION 227 
Here Calmette records that the venom of Scorpio afer, o.cooos5 gm. of which 
killed white mice in 2 hours and also a guinea-pig weighing 500 gm. in due 
time, was neutralized by the antivenin. o.cor 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 ' (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? 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. 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 
oe ar properties of the blood serum of the immunized animals. Brit. Med. Jour., 1895, 
» 1309. 
