522 COLLECTED STUDIES IN IMMUNITY. 



I should also like to mention that Kretz, 1 many years later and 

 entirely independent of me, reached exactly the same conclusions 

 as I had. His very interesting study was based on experiments 

 with diphtheria-immune horses. Following his usual tactics, Gruber 

 will, of course, draw the conclusion that the increase in the tissues 

 affinity, since it agrees with my theory, cannot really occur, and 

 he will therefore regard the entire subject as utterly fallacious and 

 best not discussed. The unprejudiced observer, however, need 

 hardly be told that it is impossible for chemical groups attached 

 to living protoplasm to maintain their affinity unchanged as though 

 they were made of stone; especially is this true if we consider the 

 varying function of the protoplasm. 



Let us take anilin as an example, and determine the combining 

 heat of the NH 2 group for a certain acid. We shall then find that 

 nearly all substitutions of the benzol nucleus, as, for instance, the 

 introduction of an amido group, a nitro group, a sulfo group, etc., 

 markedly change the affinity either positively or negatively. Thus 

 even the introduction of what is conceivably the most indifferent 

 group, the methyl radical causes a distinct and marked diminution 

 of the combining heat. Under these circumstances any one who 

 thinks chemically would consider it peculiar if a change in the affinity 

 of the cell constituents were to be regarded as something absolutely 

 inconceivable and beyond the pale of discussion. 



Since Gruber has given only that part of Madsen and Dreyer's 

 experiments which fits into his polemic, it will be necessary for me 

 to supplement this with some additional data from their study. 



These authors employed a diphtheria poison of which the fatal 

 dose for a guinea-pig of 250 grammes was 0.009, and for rabbits 

 of 1200-1600 grammes, 0.0076. Calculated per kilo this shows 

 that the rabbits were about six times as susceptible as guinea-pigs. 

 The L dose, i.e., that amount of poison, which is just completely 

 neutralized by one immune unit, was 0.6 cc. for guinea-pigs. Right 

 here I must emphasize that the L dose, as I conceive it, refers exclu- 

 sively to guinea-pigs, since according to my experiences this is the 

 only animal in which, thanks to the peculiar susceptibility, the con- 

 stants of the poison can accurately be determined. In the serum 

 mixture L all the constituents of the poison, toxin, and toxon are 

 completely neutralized, so that not only the single amount but also 



1 Zeitsch. f. Heilk., Vol. 23, 1902. 



