550 COLLECTED STUDIES IN IMMUNITY. 



different qualitatively. Guinea-pigs injected with such mixtures 

 sicken, after a long period of incubation, with typical paralyses and 

 show no local reaction. The hypothetical toxic constituent which 

 gives rise to these paralyse sis termed "toxon." 



Why then is it impossible to demonstrate the action of the toxon 

 in native diphtheria poison? This is readily explained by the relative 

 concentration of toxin and toxon in the toxic bouillon. Quantitative 

 analysis has shown that the toxin is usually much more (about 5 times) 

 concentrated than the toxon. Hence the fractional parts of the 

 lethal dose which allow the animal to live long enough to manifest 

 toxon effects usually contain too little toxon to produce the typical 

 paralyses. If, however, a large amount of poison is so far neutralized 

 with serum that all the toxin, with the higher affinity, is just bound 

 and the toxon is still free, a mixture will be obtained which practically 

 represents a pure toxon solution, for the neutral toxin-antitoxin 

 molecules play no role in an animal experiment. It is at once appar- 

 ent that, in view of the individual multiplicity of vital phenomena, 

 the poisons of all strains of diphtheria bacilli will not contain both 

 components in the same relative concentration. As a matter of fact, 

 we find that the number of lethal doses contained in the difference 

 Lf LQ varies enormously, and so far as the toxon content is con- 

 cerned the variations were from to 300% figured on the basis of 

 the toxin content. It will be well to enter somewhat more into a 

 study of these two extremes, for these striking exceptions to the typical 

 conditions argue strongly in favor of the views here presented. One 

 of the poisons in question was studied by Ehrlich, and was remarkable 

 in that the difference Lf L represented only 1.7 lethal doses. We 

 may therefore assume that the poison was free from toxon or nearly 

 so, for the value of D was actually quite near one lethal dose, the 

 figure demanded of a toxon-free poison, provided toxin and anti- 

 toxin combine like a strong base with a strong acid. The opposite 

 extreme was manifested by a poison described by Dreyer and Madsen. 

 The constants of this showed that it contained three times as much 

 toxon as toxin. This poison, moreover, gave rise to toxon effects 

 when sublethal dose of the native poison, without serum addition, 

 were injected into animals. In view of what we have said above, 

 this is readily understood, the relative concentration of toxon in 

 this case was so great that even sublethal doses sufficed to make the 

 toxon effects manifest. In most native poisons this demonstration 

 fails because of the slight relative content of toxon. 



