508 COLLECTED STUDIES IX IMMUNITY. 



injected, this will now contain 10 /io L. D. unneutralized. If now the 

 amount of antitoxin was also somewhat increased, Dreyer and Mad- 

 sen found that even with this multiple amount only toxon effects 

 were observed, the toxin now being completely neutralized and only 

 toxon remaining free. 



Dreyer and Madsen 1 thereupon subjected this same poison to a 

 thorough study, using rabbits for the purpose. They found if 0.6 cc. 

 poison was mixed with 1 I. E., that this mixture, which represents 

 the L dose for guinea-pigs, is still highly toxic for rabbits. In order 

 to render this dose of poison completely innocuous for rabbits it is 



240 

 necessary to add more antitoxin, in this case -^r I. E. The state- 



ments concerning the behavior of mixtures between these two limits 

 are also of considerable importance. A mixture of 0.6 cc. poison + 



210 



-> I. E. injected into a rabbit causes death on the twenty-second 



200 



day with paralytic symptoms. The incubation period is sixteen 



232 

 days. Even a mixture of I. E. with the same amount of poison 



caused paralyses, which appeared on the sixteenth day and con- 

 tinued for several weeks. This behavior is so important for our view 

 concerning the existence of different poisons that I must enter a 

 little more fully into the subject. According to our definition of the 



232 

 L dose, mixtures like the one containing - I. E., and therefore 



possessing a considerable excess of antitoxin, are absolutely innocuous 

 for guinea-pigs and can be injected in any quantity. In virtue of 

 the excess of antitoxin such mixtures suffice to passively immunize 

 the animal and to protect it, provided suitable doses have been in- 

 jected, against diphtheria poison and diphtheria bacilli. If then 

 such mixtures are still toxic for rabbits only one possibility remains, 

 namely, that the diphtheria poison in question contains a substance 

 which is non-toxic for guinea-pigs but toxic for rabbits. This sub- 

 stance I term toxonoid. 2 



1 See also my article in Munch, med. Wochensch. 1903, Nos. 33, 34. 



2 At the outset of my investigations I made entirely similar observations. 

 My very extensive but unpublished studies made at that time convinced me 

 that this property is not common to all diphtheria poisons, for I also found 

 some in which the L dose was exactly the same in rabbits and in guinea-pigs. 

 This fact furthermore refutes the assumption that the phenomenon described 



