72 STANDARDIZATION OF DIPHTHERIA TOXIN 



written DTN. 1 A toxin of half this strength, of which -^ c.c. 

 is the lethal dose, is written DTN . 5 . Toxins of other potencies 

 are numbered accordingly. 



Ehrlich now proceeded to define a unit of antitoxin as the 

 amount that would just neutralize 100 lethal doses of toxin : this 

 is called IU ( = immunizing unit). This amount may be contained 

 in any quantity of the serum ; thus, in that used for clinical work 

 i c.c. contains anything between 300 and 1,000 units, or even 

 more. For the purpose of testing toxins it is convenient to use 

 an antitoxic serum which is much more dilute than this, and an 

 antitoxin of unit strength is defined as one which contains i unit 

 of antitoxin in i c.c. i.e., i c.c. of the antitoxin will just neutra- 

 lize i c.c. (100 lethal doses) of standard toxin. The reaction 

 between these amounts is written thus : 



i c.c. toxin (=100 lethal doses) + i c.c. antitoxin = L , 



where L (L = limes) indicates that the mixture is a truly neutral 

 one, and that it does not kill a susceptible animal within the time- 

 limit, or produce any pathogenic action whatever. 



Now, if, as Ehrlich believes, the affinity of toxin for antitoxin 

 is a powerful one, similar to that of a strong acid for a strong 

 base, it should follow that if to the 100 lethal doses of toxin we 

 add only T 9 ^ of i c.c. of standard antitoxin, then T Jy of the original 

 amount i.e., i lethal dose should remain unneutralized, and the 

 animal should die in the same time as a similar animal which had 

 received i lethal dose and no antitoxin. 



As a matter of fact, this is not what occurs. We find that when 

 we inject the mixture the animal does not die in a short time 

 with the ordinary symptoms of diphtheritic intoxication, but 

 develops local oedema, and possibly paralysis, which may bring 

 about death at a remote period. The same thing happens if we 

 add still less antitoxin to the 100 lethal doses of toxin. To take 

 a particular case, it is not until the mixture contains less than 

 T 7 ^y of i c.c. of antitoxin that the animal dies acutely in the way 

 it does after an injection of i lethal dose of toxin. It seems, 

 therefore, that the whole of the toxicity of the toxin is removed 

 when only three-fourths of the amount of antitoxin necessary to 

 neutralize it has been added, or that a given amount of toxin can 



1 DTN = diphtheria toxin normal. It is also written DTN 1 M 250 =DTN one 

 unit for a guinea-pig (Meerschweinchen) weighing 250 grammes. 



