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, 2 after dealing with the possibility of producing immunity in human 

 subjects by administering venom per 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 3 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 

 in vitro with 5 minimal lethal doses of venom, and the mixture allowed to 

 stand 5 to'io 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. 

 8 Fraser. The limitations of the antidotal power of antivenene. Brit. Med. Jour., 1896, II, 910. 



