TWENTY-FIVE YEARS OF BACTERIOLOGY 131 



dose of dog's serum succumbed to a second dose given 

 after the lapse of some days or weeks, even when this 

 dose was sublethal for a control animal. 



Again the observation fell on stony soil, as indeed sub- 

 sequent ones were destined to do a few years later and, as 

 it now appears, chiefly because knowledge of and interest 

 in the general subject of immunity had not progressed 

 far enough at that period to present to the contemplation 

 of the "prepared mind," to use Pasteur's phrase, the 

 sharply contrasted hypersensitive state. 



But the time for the systematic investigation of the 

 phenomenon was approaching, for between 1902 and 

 1904, Richet and his pupils had their attention arrested by 

 an extraordinary incident, as it then seemed. In under- 

 taking to effect immunization with certain poisonous pro- 

 teins of animals, they found that instead of inducing re- 

 sistance, they induced hypersensibility. To this latter 

 condition they applied the name Anaphylaxis. Although 

 as it subsequently turned out, the idea involved miscon- 

 ception of the nature of the process, yet these studies 

 stand forth illuminatingly as recognizing for the first time 

 the dependence of the hypersensitive state upon a pre- 

 ceding injection of a given protein substance and the 

 necessity of an incubation period covering a number of 

 days between the injections, in order that the sensitive 

 condition might be ushered in. That the sensitizing ef- 

 fect was of the nature of a general biological reaction of 

 the animal body to the parental introduction of natural 

 proteins into the body, without reference to their primarily 

 poisonous character, came to be appreciated a little later 

 as the result of observations made on rabbits and guinea 

 pigs injected and then reinjected with horse serum, as 

 well as with other innocuous proteins. In order to arouse 

 the reaction of immunity in the animal body, some degree 

 of primary poisoning of the cells, as with bacteria, their 

 metabolic products and similar substances originating in 

 other varieties of living beings, must be accomplished;; 



