106 INFECTION AND RESISTANCE 



ingly Morgenrotli 8 again examined these relations and found that the 

 addition of a small amount of hydrochloric acid to mixtures of snake 

 poison and the antitoxin resulted in the dissociation of their union. 

 To mixtures of the venom lysin and its antitoxin, neutralized and 

 even overneutralized so that they were perfectly innocuous to suscep- 

 tible animals he added hydrochloric acid until the total concentra- 

 tion amounted to N/18. By this method a toxin-HCl modification 

 was produced which was dissociated from its union with the anti- 

 toxin and was extremely resistant to heat. In such a mixture of 

 toxin and antitoxin to which hydrochloric acid had been added, heat- 

 ing at 100 C. in a water bath for 30 minutes destroyed the ther- 

 molabile antitoxin and, after neutralization, undiminished toxic 

 properties could again be demonstrated by animal inoculation. 



These researches and other similar ones of Morgenroth, then, 

 form a satisfactory confirmation of the original experiments of Cal- 

 mette and seem to show, beyond possibility of contradiction, that the 

 inhibition of harmful properties of any true toxin, after mixture 

 with its antitoxin, does not depend upon toxin destruction. But 

 while Calmette interpreted the facts as pointing toward a failure of 

 union of the two substances, Morgenroth's work is not incompatible 

 with the conception of a neutralization of one by the other in the 

 chemical sense. These experiments of Morgenroth are of great the- 

 oretical importance moreover in that they have shown that dissocia- 

 tion of a toxin-antitoxin complex can occur. 



The nature of such neutralizations in regard to quantitative rela- 

 tions, speed of action, and relative concentrations, becomes apparent 

 partly from experiments like those mentioned above, but more espe- 

 cially from those carried out by Ehrlich with ricin and antiricin, ex- 

 periments which were primarily planned to demonstrate that the 

 reaction between a toxin and its antibody is a direct one, not depend- 

 ent upon intervention of the body cells, as at first supposed. 



It had been shown by Kobert and Stillmarck that ricin, the 

 powerfully poisonous principle of Ricinus communis (castor oil 

 bean) would agglutinate the red blood cells of a number of animals. 

 Ehrlich recognized from the beginning how closely analogous the 

 neutralization of ricin by antiricin was to that of diphtheria toxin by 

 its antitoxin. The former reaction furnished him with a simple 

 method of test tube experimentation in that the agglutinating effects 

 of ricin upon rabbits' corpuscles could be directly inhibited by the 

 preliminary addition of antiricin. A visible reaction was thus avail- 

 able, which, of course, excluded absolutely the participation of the 

 tissue cells in the antigen-antibody neutralization, and in which 

 careful quantitative measurements were possible. 



Ehrlich 9 determined by means of this method that the neutral 



8 Morgenroth. Berl. kl Woch., No. 50, 1905, p. 1550. 



9 Ehrlich. Fortschr. d. Med., Vol. 15, p. 41, 1897. 



