596 IMMUNITY 



tetanus toxins, that in certain instances the injection of j 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 actinias, 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 remark- 

 able suddenness, and that they appeared to be practically inde- 

 pendent 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 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 serum. It was afterwards 

 shown — especially by the researches of Otto and of Eosenau 

 and Anderson — that the sensitising agent had really nothing to 

 do with the toxin or antitoxin, but was contained in the normal 

 serum. 



After this brief review we may consider some of the 

 phenomena of serum anaphylaxis, as it is now called. In its 

 study horse serum has been chiefly employed, but other sera are 

 also efficient, and the guinea-pig is the most suitable test animal ; 

 the rabbit has also been used, but its relative susceptibility is 

 less than a-hundredth of that of the guinea-pig. In the case of 

 mice it is difficult if not impossible to bring about serum ana- 

 phylaxis. There is first of all the sensitising injection ; a guinea-pig 

 is injected subcutaneously with a minute quantity, e.g., - 001 c.c. 

 of horse serum, though even '000,001 c.c. has been found 

 sufficient ■ other methods of injection may also be employed. 

 After a certain number of days, usually ten as a minimum, 

 anaphylaxis has been established, and the test for this is usually 

 made by injecting subcutaneously 5 c.c. of horse serum. In 

 the anaphylactic animal severe symptoms occur ; restlessness 



