596 IMMUNITY 



of substances which are practically non-toxic in a single dose. 

 The substances which have been found to have the property of 

 calling forth this condition are of various kinds, including 

 bacteria and their toxins, animal poisons, and a great many 

 foreign proteins, e.g., those of serum, milk, egg albumin, etc., and 

 it is to be noted that they belong to the group of substances 

 which can act as antigens. Probably no body of known chemical 

 constitution originates supersensitiveness ; and, just as tolerance, 

 say to drugs, is to be distinguished from immunity, so ac- 

 cumulative action is to be distinguished from supersensitiveness. 

 Of the latter condition the earliest example observed was 

 probably the special susceptibility of tubercular patients to the 

 action of tuberculin, to which reference has already been made 

 (p. 297), and to this and like conditions the term allergy is often 

 applied. At a comparatively early date also it was found, in 

 the case of diphtheria and tetanus toxins, that in certain 

 instances the injection of a minute dose followed by another at 

 a suitable interval might be attended by serious results; and 

 that this was not an example of accumulative action, was shown 

 by the fact that the sum of the doses might amount to only 

 a fraction of a lethal dose. Richet investigated a similar 

 phenomenon in the case of a toxic substance obtained from the 

 tentacles of actiniaB, to which, from its action, he gave the name 

 of " congestin." He found that a certain time-interval between 

 the injections was necessary ; that after the second injection the 

 symptoms occurred with remarkable suddenness, and that they 

 appeared to be practically independent of the size of the first 

 dose. He applied the term anaphylaxis to the supersensitive 

 condition, and this has passed into general use ; he found also 

 that the condition lasted several weeks at least. Arthus found 

 that after repeated injections of horse serum in rabbits a stage 

 was reached at which an additional subcutaneous injection pro- 

 duced marked cedema and even necrosis, while an intravenous 

 injection, harmless to an untreated animal, brought about a fatal 

 result. The period of active research on the subject, however, 

 may be said to date from the discovery of what is now known as 

 the "phenomenon of Theobald Smith." This observer found 

 that guinea-pigs which had been treated with a neutral mixture 

 of diphtheria toxin and antitoxin might, after a certain interval of 

 time, succumb on being injected with a quantity of normal horse 

 serum. It was afterwards shown especially by the researches of 

 Otto and of Rosenau and Anderson that the sensitising agent 

 had really nothing to do with the toxin or antitoxin, but was 

 contained in the normal serum. 



