194 TOXINES AND ANTITOXINES. 



with ricine that led EHRLICH to his epoch-making researches 

 upon antitoxic immunity. 



Immunity against Ricine, EHRLICH l succeeded in rendering 

 white mice and rabbits immune against ricine by first introducing 

 small doses per os (and, in the case of rabbits, also by way of the 

 conjunctival sac), and then, after attaining a certain degree of 

 immunity, he was able by cautiously increasing the doses in sub- 

 cutaneous injection to reach a fairly high state of immunity, the 

 process taking about four months. Mice previously treated in 

 this way were capable, after eight weeks, of resisting the lethal 

 dose for a man. While a dose of 1 c.c. in a dilution of 1 : 200,000 

 per 20 grms. of body weight was absolutely fatal to the animals 

 used in control experiments, Ehrlich was able to give doses of 

 1 c.c. of solutions of 1 : 500, or even 1 : 250, to the immunised 

 animals, so that from 400 to 800 times the original immunity 

 was obtained. It was no longer possible to produce pano- 

 phthalmitis in immune animals even by the introduction of 

 large doses, although there was still a frequent occurrence of 

 the local necroses. 



Now, the serum of these immunised animals contains an anti- 

 ricine, which, just like the bacterial antitoxines, is capable of 

 combining with the ricine in vitro in such wise that both its 

 toxic and agglutinating action are prevented in accordance with 

 definite numerical laws. A special point of importance in this 

 connection is the fact, also established by EHRLICH, that the 

 same quantity of serum can influence both actions in the same 

 way. A further proof that there is here a simple combination 

 between the toxine and antitoxine has been brought by DANYSz, 2 

 who found that on treating a neutral mixture of ricine and anti- 

 ricine with proteolytic enzymes the antitoxine could be destroyed, 

 so that the toxic power again appeared ; animals that had been 

 given an exactly neutral mixture per os died of typical ricine 

 poisoning. 



EHRLICH'S fundamental experiments have since been confirmed 

 and extended by M. JACOBY 3 in a very exact and theoretically 

 far-reaching investigation. 



JACOBY agrees with EHRLICH'S conclusion that there is a true 

 quantitative combination in the action of antiricine upon ricine, 



1 Ehrlich, " Exper. Unters. iib. Immunitat," Deutsch. med. Woch., 1891, 

 976, 1218; "Zur Kenntnis d. antitox. Wirkg.," Fortschr. d. Med., 1897, 



2 Danysz, "Melanges des toxines avec les antitox.," Ann. Past., xvi., 331, 

 1902. 



3 Jacoby, "Ueber Ricinimmunitat " Hofm. Beitr. z. chem. Physiol. u. 

 PathoL, i., 51, 1901. 



