428 



Dr. Paul Ehrlich. 



so that in every case the law of equivalent projDortions would hold 

 good. 



But when looked into more closely, the relations showed themselves 

 to be by no means so simple. In what mamier could one obtain a 

 satisfactory estimation of the strength of a toxine 1 As the constant 

 factor in such an estimation, it was only possible to proceed from a 

 previously determined standard reaction in the case of a definite 

 species of animal, and so we came to regard as the " toxic unit " that 

 quantity of toxic bouillon which exactly sufficed to kill, in the coiu-se of 

 four days, a guinea-pig of 250 grammes weight. 



AMien we employed this standard imit, or " simple lethal dose," to 

 estimate the amount of toxic bouillon neutralised by one " immunity 

 unit," the facts which presented themselves were far more surprising 

 than it was possible to have foreseen at the outset. These results 

 were, that of one toxine, perhaps 20, of a second, perhaps 50, and of 

 yet a third, it might be 130 simple lethal doses were saturated by one 

 immunity unit. Since, however, we had previously assumed that the 

 simple lethal dose alone afforded a standard on which reliance could be 

 placed in determining the combining relations of toxine and antitoxine, 

 it appeared from these results that the neutralisation of toxines by 

 antitoxines did not follow the law of equivalent proportions, and> 

 notwithstanding all earlier work in agreement with such a conception 

 of the action, we were obliged to conclude that between toxine and 

 antitoxine a purely chemical affinity did not exist. The seemingly 

 inexplicable contradiction between the results just stated and preA'ious 

 work was very soon explained. Allien the neutralisation point of toxine 

 and antitoxine was investigated for one and the same sample of poison, 

 the following results were obtained. Immediately on its preparation, 

 fresh from the incitbator, it was foimd that one immunity unit neu- 

 tralised a c.c. of toxic bouillon, and this quantity represented /3 simple 

 lethal doses. AATien the same toxic bouillon was examined after a con- 

 siderable interval, the remarkable fact was discovered that exactly 

 oc c.c. of the toxic bouillon were again neutralised by one immunit}' imit 

 but tha4} these a c.c. now represented only /3 - x simple lethal doses. It 

 therefore followed that the toxic bouillon had retained exactly the 

 same combining affinity, but possessed feebler toxicity. From this it 

 was evident that the toxic action on animals and the combining 

 capacity with antitoxine represented two different f mictions of the 

 toxine, and that the former of these had become weakened, while the 

 latter had remained constant. 



Treated from the chemical standpoint, this circumstance was most 

 simply explained by assuming that the toxine was characterised by 

 the possession of two different combining groups : one, which may be 

 designated haptopliore, conditions the imion with antitoxine, while the 

 other group, which may be designated foxojjJiore, is the cause of the 



