EXPERIMENTS TO DETERMINE THE EFFICACY 
OF THE DIFFERENT CONSTITUENTS OF 
HAFFKINE'S PLAGUE PROPHYLACTIC* 
By C. BALFOUR STEWART, M.A., M.B. Camb., Thompson Yates Laboratory, 
University College Liverpool 
In Haffkine's anti-cholera inoculations in India it was noticed that, whereas the case 
incidence among the inoculated was much reduced, the case mortality was not influenced ; the 
inoculations produced a resistance against the invasion of the body by the cholera microbe, but no 
resistance against the toxins formed if they once caused infection. 
Gamaleia showed that it was possible to immunize an animal against virulent microbes 
without it being immune to the toxins of the same microbe produced artificially in the laboratory. 
Behring and Kitasato showed that by inoculating an animal with increasing doses of toxin it 
could be rendered resistant to a lethal dose. 
Haffkine acted on these observations in devising the plan of anti-plague inoculations. He 
says : 'When, in 1896, I was confronted with the problem of working out a prophylactic treatment 
against the plague, I determined to put to tlie test the ideas originated by the observation on our 
cholera patients, and to attempt, in the new preventive inoculation, to obtain at once a lowering of 
the susceptibility to the disease and a reduction of the case mortality. This I resolved to obtain 
by treating the system with a combination of bodies of microbes and of concentrated products of 
them. In giving the above considerations I beg that they should be considered as temporary, 
subject to modifications or to complete refutation. 't 
The following experiments, of whicli a preliminary note appeared in the 'British Medical 
Journal' for September 2nd, 1899, were done at the Plague Research Laboratory, Bombay, to try 
and supply experimental proof to tliis theory. 
I had previously remarked that when several rabbits were inoculated with varying doses of 
a ten-day-old living broth culture of plague those that received the larger dose showed the lesser 
mortality. Arguing that when the larger dose was given, a quantity of certain substances capable 
of conferring immunity or reducing the severity of the case were injected along with the living 
microbes, and that since a young culture was used and the microbes presumably all living, this 
substance was probably contained in the broth acted upon by the growth of the microbes, I 
proceeded to inoculate a series of rabbits with increasing doses of living plague culture in brotli. 
In some previous experiments I had found that about 2 c.cm. of Haffkine's prophylactic 
per 1,400 grams of Rabbit were sufficient to give immunity. In these experiments a smaller dose 
was taken because immunity was not wanted ; wliat I wanted to find was whether there was any 
* 'British Medical Journal,' March 3r(l, 1900. 
t A Discourse on Preventive Inoculation. Delivered at the Royal Society, Sweden, on June 8th, 1899, by W. M. 
Haffkine, CLE. 
