INFECTION AND RESISTANCE 



become more and more clear as we consider the "Side-Chain Theory" 

 which Ehrlich evolved as a result of his toxin analysis. 



Ehrlich had thus elicited facts which seemed to him to indicate 

 the presence of three qualitatively different substances in toxic fil- 

 trates of diphtheria cultures. Two of these, the toxin and the toxon, 

 were present, he assumed, in freshly prepared filtrates, as indepen- 

 dent primary secretion products of the bacilli, the toxin an acute 

 poison, the toxon a substance with slower and qualitatively different 

 poisonous effects. Both of them, toxin and toxon, possessing similar 

 haptophore groups, could unite with antitoxin and neutralize it, but 

 the affinity of toxon for antitoxon was weaker than that of toxin. For 

 this reason toxin could displace toxon from its union with antitoxin, 

 this accounting for the discrepancy between the L + and the L 

 doses. The third class of substances, the toxoids, were deterioration 

 products of toxin, the deterioration implying an alteration in the 

 toxophore group only, the haptophore group remaining the same. 



It is plain from this reasoning that Ehrlich's conception implies 

 complete analogy between chemical reactions in general and the 

 neutralization of toxin by antitoxin. Accordingly it is but another 

 step in the same direction to speculate concerning the actual rela- 

 tions of valency existing between the two substances. It seemed to 

 Ehrlich that there were many reasons for assuming that the union 

 between toxin and antitoxin occurred in proportions of 200 to 1 ; 

 that is, just as the formula for water is H 2 O, that of toxin-antitoxin 

 combinations would be "Toxin 20 oAntitoxin." 



The considerations on which this opinion was based were as fol- 

 lows: In examining a large series of toxic filtrates, Ehrlich, 15 as 

 well as Madsen, had found that the number of toxin units ("T" or 

 M L D) necessary to neutralize one antitoxin unit (that is, the 

 number of toxin units contained in the L dose) corresponded, 

 with great regularity, to multiples of 100. Values of 25, 33, 50, 

 100, etc., recurred again and again. This indicated that the de- 

 terioration of the toxin into toxoids followed a certain regularity o*f 

 progression and seemed to justify the assumption that the absolute 

 binding power possessed by antitoxin was represented by a valency 

 corresponding to a multiple of 100. Since the number of toxin units 

 contained in an Lo dose rarely fell below, and usually above 100, the 

 valency could not be less than 100. On the other hand, repeated 

 measurements of L and L + doses never showed as many as 200 

 toxin units. Ehrlich's own highest value was 133, and the highest 

 ever obtained by any one was a measurement by Madsen of 160. 

 Now considering the fact that no toxin is "pure" but that, in every 

 case, it contains admixtures of toxoid and toxon, the values 133 or 

 160 cannot represent all the valencies of an antitoxin unit. They 

 represent only that part of the antitoxin unit which is neutralized 

 10 Ehrlich.. Deutsche med. Woch., No. 38, 1898, Vol. 24, 



