RELATION OF TOXINES TO ANTITOXINES. 37 



siderably greater quantity is necessary than was the case with 

 the fresh toxine. 



Hence, it follows that the toxine solution becomes weaker on 

 keeping i.e., that the toxophore group has become inactive in part 

 of the toxine ; but since the toxine solution still requires the 

 same number of c.c. of the serum for neutralisation as before, it 

 is plain that the haptophore groups have remained intact during 

 this weakening process. From this it follows that there must be 

 present in this weakened toxine solution, substances which have 

 become non-poisonous through loss of their toxophore group, 

 although, owing to their possessing intact haptophore groups, 

 they are as capable as before of entering into combination with 

 antitoxine. 



These substances are termed toxoids l by EHRLICH. 



EHRLICH has also introduced two values of limitation which 

 he terms L (limes, "Nil") and L + (limes, "Death"). The 

 numerical significance of these terms is as follows : 



L is that quantity of the toxine solution under examina- 

 tion, expressed in toxic units (lethal doses), which, when mixed 

 with an immunity unit, is completely neutralised thereby so 

 neutralised that absolutely no symptom of poisoning appears. 

 This mixture of one immunity unit with the maximum of toxine 

 solution that can be added without the production of any 

 physiological toxic effect, is physiologically neutral. 



It is not easy to determine the point L beyond doubt, since 

 it is difficult to determine with absolute certainty whether a 

 toxine solution does or does not still exercise a slight action. 

 Hence, EHRLICH has intoduced his second value : L + is that 

 quantity of the toxine solution under examination expressed in 

 toxic units (lethal doses) which, when added to an antitoxine 

 unit, is still sufficient to kill a guinea-pig of 250 grms. in four 

 or five days. This mixture then contains a lethal dose in the 

 free state. This point can be determined with ease and certainty. 

 The difference L - L + is designated D by EHRLICH. In the 

 case of pure poisons it must obviously equal one lethal dose, but 

 in practice it is invariably greater which is a point of great 

 significance in the investigation of the constitution of toxines 

 (vide infra). 



These limitation values, then, apart from their practical use 

 in testing serum, have been of extreme value in the investigation 

 of the constitution of solutions of toxines such as diphtheria 



(quoted by Ehrlich, Deutsch. med. Woch., 1891, 978) and 

 Aronson (Berl. klin. Woch., 1893, 625) inter alias had already indicated 

 the existence of such non-poisonous, though immunising, bacterial products. 



