ANAPHYLACTOGENS 145 



At Ehrlich's suggestion, his pupil Otto took up the investigation 

 of this problem and almost simultaneously with his report there 

 appeared a detailed study of the same subject by Rosenau and 

 Anderson. From the experiments of these observers it appears that 

 the toxin in itself has nothing to do with the sensitization of the 

 animals, and that the horse serum produces this effect only if used 

 in small doses, but that the toxin in some manner which is not yet 

 understood facilitates the sensitizing influence of the serum. The 

 small size of the dose of serum which in itself is sufficient to cause 

 sensitization is indeed remarkable. In one instance Rosenau and 

 Anderson produced this result with one-millionth of a c.c., while 

 amounts ranging from ^STF to TTUT c -c. were sufficient in every 

 instance; and while a first injection of 10 c.c., which is equivalent to 

 40 c.c., pro kilo of animal caused no symptoms of any kind in the 

 guinea-pig, 0.1 c.c. as second injection was sufficient to cause death. 



Like Arthus they found the reaction to be specific in so far as it 

 was impossible to produce symptoms in animals that had been 

 sensitized with horse serum, by subsequently injecting them with the 

 serum from animals of a different species. Like v. Pirquet they 

 could also show that a certain time interval must elapse between 

 the two injections before anaphylactic symptoms develop, and that 

 this depends to a certain extent upon the point at which the first 

 injection is given; if this is made into the brain the animal becomes 

 sensitive after the eighth day, while following a subcutaneous 

 injection this occurs at least two days later. 



Antianaphylaxis. Especially interesting also was the discovery 

 that if an animal is reinjected shortly before the twelfth day the 

 reaction is only slight or may not occur at all, and that subsequent 

 injections, for a certain time at least produce no deleterious conse- 

 quences; in other words, the animal has become resistant instead 

 of hypersensitive (antianaphylaxis) . This condition, however, is 

 not permanent and after a number of weeks the animals gradually 

 become hypersensitive again. If, however, the injections are 

 repeated in increasing doses and properly spaced a state of resist- 

 ance can be produced which lasts for many months. 



Anaphylactogens. Subsequent investigations have then shown that 



an anaphylactic reaction can be called forth by the injection not 



only of blood serum, but also of milk, albuminous urine, sweat, 



bile, red cells, extracts of various normal tissues as well as of 



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