208 INFECTION AND IMMUNITY 



death " or " L + ) must simply be L plus one toxin unit. This, however, 

 was found not to be the case. Thus, in the example given, in which T 

 (the toxin unit the quantity of the bouillon killing a guinea-pig of 250 

 grams in four to five days) was equal to O.Olc.c., L (the quantity of 

 toxin completely neutralizing one antitoxin unit) was found to be 1 c.c. 

 or 100 T. In this same poison, however, L + (the quantity of toxin neces- 

 sary both to neutralize one antitoxin unit and yet to be sufficiently in 

 excess of neutralization to kill a guinea-pig of 250 grams in four or five 

 days) was not found to be merely L + IT; but^m actual experi- 

 ment proved to be L + 101 T. 



Expressed graphically, the conditions may be stated as follows: 



T= .01 c.c. of the toxin bouillon. 



L + (neutral, of 1 antitox. unit yet killing 1 pig) = 2.01 c.c. or 201 T. 



L (complete neutral, of 1 antitox. unit) = 1. c.c. or 100 T. 



Difference = 1.01 c.c. or 101 T. 



Ehrlich, at first, endeavored to explain this surprising phenomenon 

 on the basis of toxoids. He argued that the toxoids formed by de- 

 terioration of toxin might be conceived as possessing three different 

 degrees of affinity for antitoxin. If their affinity for antitoxin were 

 equal to, or more marked than, that of the toxin itself, they could have 

 no influence upon the dose L + . If, however, their affinity for antitoxin 

 were weaker than that of toxin, each fresh toxin unit added to the dose 

 L would, first uniting with antitoxin, replace a corresponding quan- 

 tity of these nontoxic substances of weaker affinity, and L + would 

 be reached only after all of these "epitoxoids," as Ehrlich called them, 

 had been replaced, and toxin became free in the mixture. 

 Thus, in analyzing our example, we have: 



100 tox.-antitox. + 100 epitox.-antitox. = L ; 



add 1 T, and we have 101 tox.-antitox. + 99 epitoxoid-anti toxin + 1 epitoxoid free; 

 add 101 T and we have 200 toxin-antitoxin + 100 epitoxoid free +1 T free = L+. 



Two fa^cts, however, led Ehrlich to abandon the opinion that epi- 

 toxoid was merely a variety of toxoid. He found, in the first place, 

 that the stated relations between L and L + were true for perfectly, 

 fresh toxin-bouillon in which little or no deterioration had taken place. 

 He observed, furthermore, that in old, altered toxin bouillon, while 

 T- was veiy much affected, the quantity needed to kill a pig con- 

 stantly increasing, and the number of actual fatal doses in L con- 



