BUPERSENSinVENESS OR ANAPHYLAXLS 559 



jections of certain substances in sub-toxic or non-toxic doses, a 

 suitable interval of time elapsing between the injections, may be 

 followed by markedly toxic or even fatal symptoms, and a similar 

 result may follow repeated injectionsof substances which are practic- 

 ally non-toxic in a single dose. In such cases, then, a condition of 

 sii] >LTsensitiveness to the particular substance has been established. 

 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 develops 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. 284). 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 actiniae, 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. Arthus found that 

 after repeated injections of horse serum in rabbits a stage was 

 reached at which an additional subcutaneous injection produced 

 marked oedema 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 



