116 JOURNAL, BOMBAY NATURAL HISTORY SOCIETY, Vol. X. 



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

 stances, 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 minimum 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 dose had been 

 attained. The subsequent doses, by gradual increments, exceeded the mini- 

 mum 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. 



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 unseen functional 

 disturbances, and it also produces visible changes. The latter are of a highly 

 irritative character, causing intense congestion in the lungs, kidneys, and other 

 organs, and, when 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 important facts have been 

 discovered by Dr. Martin, of the University of Sydney. Irritative effects are 

 obviously produced by cobra venom, even in non-lethal doses and with greatly 

 increased virulence by doses that exceed the minimum lethal ; but, in respect 

 to this action, the other three venoms used are greatly more active than the 

 venom of the cobra. Evidence was obtained to indicate that in the process 

 of immunisation a diminution occurs in the intensity of these local actions ; 

 but this diminution does not proceed so rapidly as that in the unseen functional 

 or other changes which are the more direct causes of death ; and, further, 

 the local irritative changes, after having been produced, are slower to disap- 

 pear than the unseen functional disturbances. Until these facts had been 

 appreciated, and, indeed, even with the adoption of the precautions suggested 

 by them, frequent failures occurred. The apparently contradictory results 

 accordingly were obtained of the production, by gradually increasing doses, 

 on the one hand, of a protection against quantities much above the minimum 

 lethal, so perfect that no apparent injury was caused ; and, on the other hand, 

 of an intolerance so decided that death was produced by the last of a succes- 

 sion of gradually increasing doses, no one of which was so great as the mini- 

 mum lethal. The latter unfortunate event was frequently displayed in 

 guinea-pigs, and attempts to carry immunisation in them to a high point were 

 found to be extremely difficult. 



