ANAPHYLAXIS 235 



intense, and more rapid ; they appear within an hour, or even 

 within a quarter of an hour, after the injection. 



In the light of these observations V. Pirquet observed later 

 that the unknown germs of vaccine lymph produce a premature 

 reaction in the skin of those individuals formerly vaccinated 

 and now supersensitive. The same observation in its turn 

 suggested to him the idea of applying a droplet of tuberculin 

 to the skin of a tuberculous patient to test his susceptibility, 

 and this was the origin of the cutaneous reaction of 

 tuberculosis. 



Through these observations the study of anaphylaxis entered 

 the sphere of human medicine, and the important question 

 arose. How are we to render harmless our therapeutic sera? 



Serum Anaphylaxis in the Guinea-pig. The 

 Phenomenon of Th. Smith. — The question entered the 

 laboratories when attempts were made to elucidate the fact 

 observed in the American serotherapeutic institutes, that 

 guinea-pigs which had already been employed in the titration 

 of antidiphtheritic serum (injected with a mixture of toxin and 

 serum) became eventually supersensitive to horse serum. 

 If three to twelve weeks after the titration injection 5 c.c. of 

 horse serum is injected under the skin or especially into the 

 peritoneum, the animals immediately manifest anxiety and 

 discomfort ; respiration is rapid and laboured, the heart 

 becomes weaker, the temperature falls below normal and after 

 one hour 50 per cent, of the animals die, whereas normal 

 guinea-pigs support doses of the same serum five times as great 

 without any disturbance. The phenomenon is specific, for 

 guinea-pigs receiving horse serum in the first dose behave 

 on re-injection quite like normal guinea-pigs towards rabbit, 

 goat or ox serum. In the toxin -I- antitoxin titration mixture 

 the antitoxin, i.e., the horse serum, is responsible for the 

 supersensitiveness induced. A small dose sensitizes more 

 certainly than a large dose; even one millionth of a c.c. 

 may suffice ! The symptoms resemble serum-sickness in man ; 

 there is an incubation period of twelve days at least after the 

 first injection. The supersensitive conditiori persists for 



