TOXOID. 



75 



I. E., as is done in the L + , the antitoxin, on account of its greater attrac- 

 tion for the toxin, will combine with the latter and leave the toxon free to 

 subsequently carry out its own functions. The more crude poison is added, 

 the more toxon remains unbound, until a point is reached when no more 

 toxin can be taken up and consequently some is left unneutralized. If the 

 amount of active toxin reaches the dosis letalis minima, it is sufficient to 

 kill the animal and thus the limes -f is attained. 



When, instead of freshly prepared toxins Ehrlich employed older bouillon 

 cultures, the poisonous qualities distinctly sank to about one-half, but the 

 surprising fact was that the L + had not been altered and even though it 

 had lost one-half of its toxic power, it had still retained its initial potential- 

 ities for neutralizing antitoxin. 



Ehrlich's explanation was that the diphtheria poison consists of two 

 Toxoid. molecular groups; one the carrier of the toxic qualities, and therefore 

 known as the "toxophore" group, the other uniting with the antitoxin 

 and having the capability of neutralizing it, known as the "haptophore group." The 

 toxophore group is very labile, while the haptophore group strongly in contrast to it, is char- 

 acterized by its stability. The toxophore element destroyed, the diphtheria poison loses 

 its toxic qualities, but retains its power to bind antitoxin. A non-poisonous diphtheria 

 toxin possessing such power, is designated by Ehrlich as " Diphtheria Toxoid." 



The mode of standardization of serum advocated at the present day is ap- 

 plicable exclusively to the L -f- dose. It is effected by injecting guinea-pigs 

 subcutaneously with mixtures of various doses of diphtheria toxin on hand, 

 plus an anti-toxin unit, and noting the smallest amount of toxin which kills the 

 animal in four to five days. This L -f- as the constant factor is now mixed 

 with different amounts of the serum to be tested and that quantity deter- 

 mined which just prevents the death of the animal. If for example i/ioo 

 c.c. is necessary, this serum is considered one hundred times as strong 

 as the standard antitoxin unit, or in other words it contains 100 immunity 

 units. 



This method of Ehrlich has been adopted not only in Germany, but almost in all 

 other countries in Europe and also in America. Only in France the principle varies 

 somewhat, as here the serum is tested both for its protective and curative action. The 

 protective power of a serum is considered 50,000 if o.oi c.c. of a serum saves a guinea- 

 pig weighing 500 gm. from the fatal consequences following a dose of toxin sufficient to 

 kill an animal of the same weight in thirty to forty hours. The standard therefore 

 takes into consideration the relation between the amount of serum and the weight of 

 the animal. The serum is injected into the guinea-pig twelve hours before the toxin and 

 the animal should not lose in weight during the following six days. The curative 

 power is estimated by injecting a guinea-pig with a dose of toxin (sufficient to kill a 

 control animal in thirty to forty hours) and six hours afterward the serum is injected. 

 The animals remaining alive on the sixth day are considered as cured. 



The French method of standardization is built upon the belief of Roux 

 that no parallelism necessarily exists between the protective and curative 

 values of a serum. Kraus and Schwarz have recently published accounts 



