1894 - 95 .] Antivencne and Immunization against Venom. 455 
also produces visible changes. The latter are of a highly irritative 
character, causing intense visceral congestions 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 immuniza- 
tion, 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 disappear than the unseen functional dis- 
turbances. 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, of an intolerance so decided that death was 
produced by the last of a succession of gradually increasing doses, 
no one of which was so large as the minimum-lethal. The latter 
unfortunate event was frequently displayed in guinea-pigs, and 
attempts to carry immunization in them to a high point were found 
to be extremely difficult. 
Notwithstanding these difficulties, however, such gratifying 
results have been obtained as that rabbits could at last receive, by 
subcutaneous injection, so much as ten, twenty, thirty, and even the 
remarkable quantity of fifty times the minimum-lethal dose, with- 
out manifesting any obvious symptoms of poisoning. (See Diagram.) 
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 administra- 
tion of even non-lethal doses, in non-protected animals ; and a loss 
