74 TOXIN AND ANTITOXIN. 



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

 fatal doses, i c.c. of this normal curative serum represents one immunity 

 or antitoxin unit. 



The present antitoxin unit was fixed by Ehrlich who 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 

 gm. 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 O, 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.c. 

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

 LO was found to be 0.42 c.c. =108 lethal doses. 



Difference 0.06 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 has only a 

 Toxon. slight affinity for the antitoxin. It is this body which is prob- 

 ably the cause of the paralysis occurring weeks after the infection. 

 In a mixture like L O, the antitoxin has fully neutralized both the toxon 

 as well as the toxin. If, however, more diphtheria poison is added to the 



