TOXIN AND ANTITOXIN 523 



high multiples of this can be injected into guinea-pigs without causing 

 a trace of local or general reaction. If the same amount of poison, 



i a ^ 



0.6 cc., was mixed with I. E. instead of with one I. E. it was 



found that the toxin fraction had practically been completely neu- 

 tralized, leaving only the toxons, characterized by the develop- 

 ment of paralyses. Just in this poison Madsen and Dreyer have 

 shown that the difference between toxin and toxon is qualitative 

 and not quantitative. They found that mixtures of poison and 

 antitoxin, which were near the limit of toxin neutralization, showed 

 only toxon action when given in small doses, whereas when the mix- 

 ture was increased tenfold, death occurred from toxin. 1 



//, however, the quantity of antitoxin was also slightly increased, 

 even the tenfold multiple showed only toxon action. From these data 

 we see that the poison consisted of about 167 units toxin-toxoid 

 and 33 units toxon. 



This same poison was subjected to a thorough investigation on 

 rabbits by Dreyer and Madsen and gave the following results: If 

 0.6 cc. poison are mixed with one I. E., it will be found that this 

 mixture, which represents the L dose for guinea-pigs, is still highly 

 toxic for rabbits. In order to render this amount of poison com- 

 pletely innocuous for rabbits it is necessary to add more antitoxin; 



240 

 as a matter of fact it requires - I. E. Their statements concern- 



ing the behavior of mixtures between these two limits are also very 



210 

 interesting. A mixture of 0.6 cc. poison + - I. E. given to a rabbit 



gives rise to paralytic phenomena appearing on the fifteenth day 

 and ending fatally on the twenty-second day. Even a mixture of 



232 

 the same dose of poison with I. E. produced paralysis com- 



mencing on the sixteenth day and continuing for several weeks. 

 In view of the importance of these facts for the conception of a plu- 

 rality of poisons, I cannot pass on without discussing them more 

 fully. According to our definition of the L dose, such over-neu- 



1 The explanation of this is that the toxon determination by means of 1 1. E. 

 naturally cannot be an absolutely exact one, small residual amounts of toxin, 

 e.g., 1/10 lethal dose, readily being overlooked. If, however, an appropriate 

 multiple, say ten times this mixture, be injected, this will contain ten times 

 1/10 fatal dose. 



