RELATION OF TOXINES TO ANTITOXINES. 45 



degrees of affinity. This has been done by EHRLICH and 

 subsequently by MADSEN (loc. cit.) in the following manner : 

 If an immunity unit were added to 200 saturation units (i.e., 

 100 toxic units in the case of fresh poisons), the mixture would 

 be physiologically absolutely neutral (L ). If now the quantity 

 of antitoxine added to the same solution of mixed poison were 

 to be reduced, a measured fraction of one immunity unit (200 

 units of combination) being added, the toxic characteristics 

 would gradually appear again, since there would be an excess 

 of free toxine. If the poison bouillon consisted of pure toxine, 

 one toxic unit would be liberated by the reduction of the 

 antitoxine to the extent of one unit of combination, two toxic 

 units if the reduction amounted to two units of combination, 

 and so on, until eventually the whole of the toxine had been 

 liberated. If the poison bouillon contained, in addition to the 

 toxine, only non-poisonous haptines of equal affinity, every 

 diminution to the extent of one unit of combination would 

 liberate a fraction of a toxic unit ; but this phenomenon would 

 occur quite regularly ; so that if 10 toxic units were set free by 

 a reduction to the extent of 20 units of combination, 50 would 

 be liberated if the units of combination were reduced by 100. 

 The result would be totally different, however, when substances 

 of different affinity were present, tinder such conditions the 

 first effect of the reduction in the units of combination would be 

 to liberate the haptines possessing the smallest affinity (toxones], 

 next those with medium affinity (toxines and syntoxoids), and, 

 last of all, those with the greatest degree of affinity (protoxoids). 

 Or, to express it differently, if a given solution of the mixed 

 poison were to be treated with increasing amounts of antitoxines, 

 the protoxoids would be saturated first, then the toxines, and 

 finally the toxones. 



Now these theoretical requirements can be proved by experi- 

 ment. If we proceed from 200 : 200 no toxine activity appears 

 up to a certain stage, but only the quite distinct toxone activity 

 mentioned above (zone of free toxones). But if we go beyond 

 this limit the results are different according as the poison still 

 contained only toxines (fresh poisons), or also syntoxoids and 

 protoxoids in addition to toxines. 



In the first more simple case each reduction by -^-^ immunity 



ZOO 



unit (one unit of combination) then liberates one lethal dose, and 



this continues to the end. Usually this limit is at -^ - ; thus 



ZOO 



we have then 



