RELATION OF TOXINES TO ANTITOXINES. 35 



that eventually every " single lethal dose " of poison would cor- 

 respond to a definite number of "antitoxine units" For this 

 purpose the strength of the solution might be readily calculated 

 upon the known toxicity of 1 c.c. of a solution to be taken as 

 unity (normal poison). Unfortunately, this is beyond the range 

 of practicability. Almost every solution of toxine stands in a 

 different proportion toward the amount of antitoxine required 

 for its neutralisation, when the ratio of a "lethal dose" to the 

 number of " antitoxine units " is calculated. 



Here we are face to face with the most extraordinarily com- 

 plicated conditions, and there still remain certain obscurities and 

 difficulties to be explained, although the confusion has been 

 for the most part cleared up by the painstaking researches of 

 EnRLiCH. 1 In the first place, the rapidity with which toxine 

 and antitoxine combine depends not only on their nature but 

 also on the concentration of the two components (vide supra}. 

 But, above all, it has been found that every bouillon of diph- 

 theria virus contains, in addition to the specifically active toxine, 

 varying proportions of other substances which possess the hapto- 

 phore, though not the toxophore, group of the true toxines, and 

 which, therefore, make the same demand upon the antitoxine as 

 the toxine itself, although they have no influence upon the lethal 

 dose the toxic effect of the poison. Thus, in determining the 

 unit of measurement, the single lethal dose, these substances 

 escape observation, but their influence is immediately manifested 

 when an attempt is made to determine the amount of a given 

 antitoxine solution required to neutralise this single lethal dose. 



If a pure solution of toxine would require a given number of 

 c.c. of a standard solution of antitoxine, this number would be 

 increased in proportion to the quantity of these non-poisonous, 

 though antitoxine-consuming, substances in the impure toxine 

 solution. Hence, the varying amount of these substances in 

 every solution of toxine enormously increases the difficulty of 

 establishing the absolute constancy of these proportions, as 

 demanded by the side-chain theory ; and these difficulties have 

 not yet been completely overcome in every case. 



In order to obtain a clear idea of the immediate factors in this 

 question it is necessary for us to begin with the physiological 

 units of measurement devised by BEHRING and EHRLICH for the 

 study of the action of antitoxines. The numerical definitions 

 fixed for diphtheria virus are as follows : 



1 Ehrlich, "Die Wertbemessung des Diphtherieserums," Klin. Jahrb., 

 vi., 299, 1899; "Ueber die Constit. des Diphtheriegiftes," Deutsch. med. 

 Woch., 1898, 597. 



