TOXIN AND ANTITOXIN 109 



new M L D or "T" (that is: toxic unit) the quantity of toxin 

 which will kill a guinea pig of the designated weight in from 4 to 5 

 days. He then determined for a number of poisons the exact quan- 

 tity just neutralized by one antitoxin unit, calling this quantity L . 

 (L meaning Limes or threshold.) 



It is clear that in judging of complete neutralization of a quan- 

 tity of toxin by antitoxin, there may be a strong subjective element, 

 since any very slight excess of toxin may cause unimportant local 

 reactions such as edema or small hemorrhages, which could escape 

 the attention of one observer while being noticed and recorded by 

 another. In order therefore to exclude definitely all subjective fea- 

 tures from such experimentation, Ehrlich now established another 

 toxin value L + dose ("Limes death" now, for convenience, writ- 

 ten L + ) which eliminated all possible variations of personal per- 

 ception. He designated by this symbol that quantity of toxin which 

 not only neutralized one antitoxin unit but included enough toxin, 

 in excess of this, to give the result of one free toxin unit, that is, to 

 cause death in 4 to 5 days in a guinea pig of 250 grams. Since 

 the three values just defined form the basis of Ehrlich's experiments 

 as well as that of all practical diphtheria serum standardizations we 

 will briefly restate them for the sake of clearness. 



Thus: 



M L D or "T" = the amount of toxin which, subcutaneously injected, 

 causes death in a 250-gram guinea pig in from 4 to 5 days. 



L = the amount of toxin which is just neutralized by one antitoxin unit so 

 that no trace of reaction, local or otherwise, ensues 



and 



L+ = that amount of toxin which will cause death in 4 to 5 days in a guinea 

 pig of 250 grams if injected together with one antitoxin unit. 



It will further clarify the meaning of these terms to examine 

 experimental protocols which show how these values are determined. 

 Thus in the following: 



I. Injections of toxin 



(1) .005 c. c. guinea pig lives. 



(2) .009 c. c. guinea pig dies in 6 days. 



(3) .01 c. c. guinea pig dies in 4 days. 



(4) .02 c. c. guinea pig dies in 2 days. 

 .01 = M L D or T. 



II. 1 Antitoxin unit + .19 toxin = late paralysis. 



1 Antitoxin unit + .20 toxin = sometimes late paralysis and sometimes 



acute death. 



1 Antitoxin unit + .21 toxin = death fourth day. 

 1 Antitoxin unit + -22 toxin = death in 2 to 3 days. 

 .21 = L+ dose. 



