228 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 
of serum failed to protect, but 2.5 and 3 c.c. saved the animal; 4 c.c. of the 
serum per kilo body-weight was able to save the animal, when given 30 
minutes before, from a little more than the minimal lethal dose of venom. 
It was also shown that 1.5 and 0.8 c.c. of antivenin injected 30 minutes after a 
lethal dose will save the animal, and that 5 c.c. will save it from twice the 
lethal dose. 
Fraser found, as Calmette had done, that the antivenin made by using 
cobra venom was efficacious against various kinds of venoms. In regulating 
the dose of antivenin he urges that the dose be calculated by using cats and 
not herbivorous animals, which are so highly susceptible. He 1 believes that 
the difference in the degree of susceptibility to venom of carnivorous and her- 
bivorous animals is much dependent on the diet. ‘Thus after feeding white 
rats on meat for seven weeks he found that their resistance to venom was 
greatly raised. In the same article Fraser recommended that the antivenin 
be injected into the bitten part before the ligature is removed. The dose of 
antivenin for use in medicine for man was fixed by him at 20 c.c., although 
this standard was abandoned by him a little later. 
Fraser,’ after dealing with the possibility of producing immunity in human 
subjects by administering venom fer os, entered a rather pessimistic warning 
by stating that the estimated dosage of antivenin is such as to make it scarcely 
practicable in human therapeutics. He recommended 350 c.c. as the quantity 
necessary to cure a man of 170 pounds. In a subsequent paper he once more 
laid bare his view as to the possible therapeutic value of antivenin. Calculated 
from his experimental data he believes that about 300 c.c., at least, of the 
serum would have to be injected in order to save a man from a single lethal 
dose of venom. He expressed fear that this enormous quantity of the anti- 
venin would render its clinical application almost impracticable. 
Fraser* points out a very important fact concerning the venom-antivenin 
reaction, viz., that when 1.3 c.c. of antivenin per kilo body-weight is mixed 
im vitro with 5 minimal lethal doses of venom, and the mixture allowed to 
stand 5 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 the chemical nature of the reaction. He denies the 
probability that leucocytes are active in protecting the venomized body against 
the venom, being stimulated by the antivenin. He thinks the theory of 
vital nature untenable, and expresses his belief that protection or immunity 
is chiefly due to the accumulation in the blood of an antidotal substance, and 
that this substance originates, at least in part, from the venom itself and is 
normally a constituent of the venom. 
Encouraged by the favorable results of his experimental serum therapy 
on small animals with the antivenin obtained from various laboratory animals, 

1 Fraser. The treatment of snake poisoning with antivenin derived from animals protected against 
serpents’ venom. Brit. Med. Jour., 1895, II, 416. 
2 Fraser. Address on immunization against serpents’ venom and the treatment of snake bite with 
antivenene. Brit. Med. Jour., 1896, I, 957. 
* Fraser. The limitations of the antidotal power of antivenene. Brit. Med. Jour., 1896, II, gto. 
