DIPHTHERIA. 223 



are of great importance for the characterization of the 

 toxin. The first (L ) represents that amount of toxin that 

 is neutralized by the serum, so that injection of the mixture 

 is borne by the guinea-pig without injury. The second 

 limit (L + ) represents the amount on injection of which such 

 a marked excess of toxin is rendered active in spite of the 

 presence of the anti-body that death of the guinea-pig takes 

 place within four days. According to the foregoing con- 

 siderations, L - represents about 100 lethal doses; for, as 

 has been explained, if the antitoxin-unit DAN 1 neutralizes 

 the toxin-unit DTN l , that is i cu. cm. of that toxin of 

 which o.Oi cu. cm. destroys a guinea-pig weighing 250 

 grams ; and the difference (D) between the two limits (L 

 and L + ) should be equal to the minimal lethal dose. These 

 assumptions are, however, not justified, as Ehrlich has shown 

 as the result of most painstaking experiment. L varies be- 

 tween 27 and 109 toxin-doses, and D between i, 7, and 28. 

 Ehrlich, upon the basis of experiments with tetanus, had 

 already come to the conclusion that by the action of carbon 

 disulphid tetanus-toxin could be transformed into an in- 

 nocuous modification, but which is still capable, both in the 

 test-tube and in the animal body, of combining with the 

 anti-bodies. The spontaneous attenuation of the diphtheria- 

 toxin so frequently encountered, without the slightest dimi- 

 nution in its neutralizing activity, is attributed by Ehrlich 

 to a similar transformation of a portion of the toxin into 

 such toxin- modifications, and for these he proposes the 

 name of toxoids. 



Ehrlich divides the toxoids into three groups : (i) Pro- 

 toxoids, which unite with the antitoxin more easily than 

 the toxin ; (2) syntoxoids, which exhibit for the antitoxin 

 the same affinity as the toxin ; and (3) epitoxoids, which 

 possess a lesser attraction for the antitoxin. As the pro- 

 toxoids possess a greater affinity for the anti-bodies than, and 

 the syntoxoids the same affinity as, the toxin, they can not 

 be displaced by the toxin from their combination with the 

 anti-toxin. If, therefore, the neutral toxin-antitoxin-mixture 

 (L ) consists of toxins, protoxoids, and syntoxoids, then 

 L + is produced by the addition of the simple lethal dose, 

 or, what amounts to the same thing, D, the difference be- 

 tween L and L + is equal to this lethal dose. The condi- 

 tions are, however, quite different when epitoxoids are 

 present. These must, in the first place, be displaced by the 



