488 COLLECTED STUDIES IN IMMUNITY. 



far less basic trimethylamin, methyl alcohol being split off in the 

 process. Let us take a certain definite quantity of tetramethylam- 

 monium hydroxid, say 20 molecules, and determine the quantitj 7 

 of boric acid which will just suffice for complete neutralization, as 

 shown by a suitable indicator. On changing the ammonium base 

 into the tertiary amin (a change which we shall assume to be com- 

 plete) we shall find that a larger quantity of boric acid is necessary 

 for neutralizing the tertiary amin. In other words, there has been 

 a change in the position of the neutral point, although the number 

 of basic radicals remains the same. This necessarily follows from the 

 decrease in affinity brought about by the transformation. 



The reverse will take place if a weak base is transformed into a 

 stronger one. A change in the position of the neutral point will occur 

 even if the transformation is only a partial one, i.e., does not affect 

 the entire number of molecules. If, however, in spite of an extensive 

 formation of toxoid, we find the test limits unchanged, we can only 

 conclude that any considerable change in affinity has not occurred. 

 We shall subsequently learn of another fact, which affords conclusive 

 evidence of the correctness of these views. 



Our next problem will be to study the influence of the toxoids 

 on the neutralizing process. To begin, it should be remarked that 

 the bacterial poisons with which we are dealing are not, as a rule, 

 pure poisons. By this, of course, I do not mean to deny that pure 

 poisons can occur. If the toxophore group possesses considerable 

 resistance so that it is not affected by the processes used in its pro- 

 duction (keeping in the incubator for weeks, etc.), it will be possible 

 to obtain poisons which contain only toxins and no toxoids. Such a 

 result however, can probably only be counted on in a small number 

 of isolated cases, and is not obtained as a rule. So far as diphtheria 

 poison is concerned, of which I have made a special study, I have 

 never yet, among a large number of specimens examined, found a 

 single one free from toxoids. In estimating the degree of purity 

 one proceeds by finding in various poisons how many fatal doses 

 (L. D.) are neutralized by one immune unit (I. E.). The maximum 

 value in the poisons at my disposal was 130, but Madsen has described 

 a poison in which the Lf dose contained 160 L. D. But even this 

 poison, as I shall show later, 1 merely approached tine character of a pure 

 poison. 



1 It is especially important that even diphtheria poisons which have been 



