114 Professor Thomas B. Fraser [March 20, 



guinea-pig, rabbit, white rat, cat, and the innocuous grass snake of 

 Italy {Tro'pedonotus natrix). Very considerable diiferences were 

 found to occur in the minimum-lethal dose for each of these animals. 

 For the guinea-pig, the minimum-lethal dose per kilogramme was 

 • 00018 grm. ; for the frog, • 0002 grm. ; for the rabbit, • 000245 grm. ; 

 for the white rat, '00025 grm.; for the cat, somewhat less than '005 

 grm. ; and for the grass snake, the relatively large dose of * 03 grm.* 

 Cobra venom thus takes a position among the most active of known 

 substances, rivalling in its lethal power the most potent of the 

 vegetable active principles, such as aconitine, strophanthin or 

 acokantherin. 



These facts having been ascertained, attempts were next made to 

 render animals proof against lethal doses, by administering to them 

 a succession of gradually increasing non-lethal doses. These were, 

 for the first few doses, in some of the experiments, one-tenth of the 

 minimum-lethal, in others one-fifth, in others one-half of the mini- 

 mum-lethal, and in others almost as great as the minimum-lethal. 

 At varying intervals the doses were repeated, and by-and-by gradually 

 increased, until the actual minimum-lethal had been attained. The 

 subsequent doses by gradual increments exceeded the minimum-lethal, 

 and after five or six times the minimum-lethal had been reached, it 

 was found that the increments could be increased so that each became 

 twice, four times, and latterly even five times the minimum-lethal, 

 and still the animal suffered little, and, in many cases, no appreciable 

 injury. ^ 



This brief statement, however, does not represent the experi- 

 mental difficulties that were encountered. It describes the course of 

 events in the altogether successful experiments. Non-success, how- 

 ever, was frequent, and many failures occurred before experience 

 indicated the precautions and conditions that are necessary for 

 success. 



Serpents' venom exerts what may broadly be described as a duplex 

 action. It produces functional disturbances unassociated with visible 

 structural changes, and it also produces obvious structural changes. 

 The latter are of a highly irritative character, causing intense vis- 

 ceral congestions in the lungs, kidneys, and other organs, and when 

 the venom is given by subcutaneous injection, on all the structures of 

 the skin and subjacent parts. There are apparently also some definite 

 changes produced in the blood, with regard to which several impor- 

 tant facts have been discovered by Dr. Martin, of the University of 

 Sydney, and by Surgeon-Colonel Cunningham, of Calcutta. Irrita- 

 tive effects arc obviously produced by cobra venom, even in non-lethal 

 doses, and with greatly increased virulence by doses that exceed the 



* Guinea-pig, nearly a milli§ 



Kabbit, nearly \ „ 



White rat, \ „ 



Kitten (6 weeks), 2 miliig. 

 Cat, 5 „ 



Grass snake, 3 centig. 



