80 TOXIN AND ANTITOXIN 



A normal curative serum is one of which o.i c.cm. suffices to neutralize 

 i c.cm. of Behring's normal poison, i.e., is able to overcome the effect of 100 

 fatal doses, i c.cm. of this normal curative serum represents one immu- 

 nity or antitoxin unit. 



The present antitoxin unit was fixed by Ehrlich. He adopted that 

 amount of antitoxin as his standard, which when mixed with 100 times the 

 lethal dose of a then existing toxin, and injected into an animal, was 

 sufficient to so neutralize the toxin that not the slightest evidence of 

 either a local symptom or general illness was present. Ehrlich chose 

 the antitoxin rather than the toxin as the constant of standardization, 

 because the toxin would deteriorate after some time, while the antitoxin 

 could be preserved in a stable, unchangeable form. 



In spite of this fact, the new method of titration was still unsatisfactory, 

 inasmuch as the toxin could undergo other biological changes not yet 

 taken into account. To understand these, the acquaintance of several 

 new terms is essential, and they are, dosis eerie efficax, limes + or limes 

 death, limes o or limes zero. 



While the dosis letalis minima represents the smallest dose of toxin 

 which may be fatal in four to five days, the dosis certe efficax (dose of 

 certain efficiency) stands for the smallest dose which will surely kill any 

 pig of 250 gms. within this period of time. 



By limes -[-(limes death) is meant the smallest amount of toxin which 

 after being mixed with an antitoxin unit, will still cause the death of a 

 guinea-pig within four to five days. By limes o (limes zero) is understood 

 the dose of toxin which is just neutralized by one antitoxin unit (I. E. = 

 antitoxin unit or "Immunitats Einheit"), so that no toxin is free and the 

 animal remains perfectly well. Limes + therefore implies an excess of 

 poisonous toxin; L 0, perfect neutralization. 



Theoretically speaking, the difference between L+ and L O should 

 represent the minimum lethal dose (d. 1. m.). This, however, is almost 

 never so, as is shown in the following illustration. 



The d. 1. m. of a certain poison was estimated as 0.0039 c.cm. 



L+ was found to be 0.48 c.cm. = 123 lethal doses. 



L was found to be 0.42 c.cm. = 108 lethal doses. 



Difference 0.06 c.cm.= 15 lethal doses. 



In order to explain this phenomenon Ehrlich considered that there 



were two other substances contained within the diphtheria bouillon in 



addition to the diphtheria toxin; namely, diphtheria toxon and diphtheria 



toxoid. The toxon is a poison which in contrast to the toxin 



Toxon. has only a slight affinity for the antitoxin. It is this body 



which is probably the cause of the paralysis occurring weeks 



after the infection. 



