THE CONSTITUENTS OF DIPHTHERIA TOXIN. 491 



A and B: ?+^ or J+-T- represent analogues of solutions containing 



also toxoids. In all of these mixtures the end point of neutralization 

 will be practically constant. If, however, the affinities of A and B 

 for hydrochloric acid are not exactly equal the neutralization will 

 proceed in a straight line only if we are dealing with the pure alkaloid. 

 In all other cases it will follow the course of a curve whose character, 

 of course, is dependent on the relative amounts of the two com- 

 ponents. 



This problem of the simultaneous neutralization of two alkaloids 

 has been studied in suitable cases by J. H. Jellet. Let us take the 

 neutralization of quinine and codein with hydrochloric acid, in which 

 the coefficient of equilibrium / = 2.03. For the sake of simplicity 

 I have assumed this to be 2.0. In order, furthermore, to have the 

 conditions as simple as possible, let us take as an example a mixture 

 of 100 molecules quinine and 100 molecules codein. These will then 

 be neutralized by 200 molecules hydrochloric acid. By means of 

 the formula devised by Jellet one next determines how much quinine 

 is transformed into the salt by each successive addition of one-tenth 

 the entire neutralizing dose (20 molecules HC1). It will be found 

 that the first tenth neutralizes 13 and the last tenth 7 molecules 

 of quinine, while the course of the neutralization of the quinine is 

 itselt entirely uniform. If another combination is taken, in which 

 the second alkaloid possesses a weaker affinity, so that K = 1Q, it can 

 easily be calculated that under these circumstances the first tenth 

 hydrochloric acid neutralizes 17.8, the last tenth only 3 molecules 

 of quinine. On representing these reactions graphically we shall 

 obtain curves entirely similar to those representing the neutralization 

 of a weak base with a weak acid, and it would probably not be difficult 

 to find a combination of alkali and acid whose curve corresponds to 

 the alkaloid curve mentioned. 



Hence, if such a mixture of alkaloids together with the appro- 

 priate neutralizing agent (acid) were given one for a biological titra- 

 tion, and if, furthermore (to make the analogy with toxin-antitoxin 

 determination complete), the employment of any additional chemical 

 aids was barred, the neutralization curve obtained under such stringent 

 conditions could easily give the impression that one were dealing 

 only with the neutralization of two substances possessing weak affini- 

 ties. Nevertheless, even under these limitations, it is possible to 

 learn the true conditions if, as I have done, one does not confine one's 



