1896.] on Immunisation against Serpents' Venom. 115 



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 func- 

 tional or other changes which are the more direct causes of death ; 

 and, further, the local irritative changes, after having been produced, 

 are slower to disappear than the unseen functional disturbances. 

 Until these facts had been appreciated, and, indeed, even with the 

 adoption of 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, 

 when the intervals of time separating successive doses had been too 

 brief, of an intolerance so decided that death was i)roduced by the 

 last of a succession of gradually increasing doses, no one of which 

 was so great as the minimum-lethal. The latter unfortunate eveut 

 was frequently displayed in frogs and guinea-pigs, and attempts to 

 carry immunisation in them to a high point usually resulted in 

 failure. 



Notwithstanding these difficulties, however, such gratifying results 

 have been obtained as that rabbits could at last receive, by sub- 

 cutaneous injection, so much as ten, twenty, thirty, and even the 

 remarkable quantity of fifty times the minimum-lethal dose, without 

 manifesting any obvious symptoms of poisoning. 



Almost the only observable phenomena were a rise in the body 

 temperature, which continued for a few hours after the injection, and 

 which contrasts with the fall that occurs after the administration of 

 even non-lethal doses, in non-protected animals ; and a loss of appe- 

 tite, which usually, though not invariably, occurred, and was probably 

 the cause of a temporary fall in weight during the day or two days 

 succeeding each injection. On the other hand, during the process of 

 successful immunisation, the animals increased in weight, fed well, 

 and appeared to acquire increased vigour and liveliness. 



It is marvellous to observe these evidences of the absence of 

 injurious effects, and even of the production of benefit in an animal 

 which, for instance, has received in one single dose a quantity of 

 venom sufficient to kill, in less than six hours, fifty animals of the 

 same weight, and in the course of five or six months a total quantity 

 of venom sufficient to destroy the lives of 370 animals of the same 

 species and weight (Fig. 1, overleaf). 



With the cobra venom I have also immunised cats and white rats, 

 both by subcutaneous and by stomach administration ; but the sig- 

 nificance of the latter method of administration will be afterwards 

 considered. A horse has also been immunised ; and I have to express 

 my obligations to Principal Williams and Prof. W. Owen Williams 

 for granting me the accommodation of their establishment, and to 



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