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86 ARRHENIUS* AND MADSEN'S VIEWS 



On this theory many facts which were formerly very difficult 

 to explain become quite simple. Take, for instance, the exact point 

 of neutralization of toxin by antitoxin as seen in the determina- 

 tion of the L dose : this has always been a matter of great 

 difficulty a difficulty formerly explained by assuming the last 

 substances to be neutralized are the toxons, which have a very 

 feeble and indefinite pathogenic action. On the physical chemistry 

 theory the difficulty disappears, because there is no point of exact 

 neutralization. In spite of the presence of an excess of antitoxin, 

 some dissociation of the toxin-antitoxin molecule will always 

 occur, and the mixture will always contain free toxin, though in 

 very small amount. Further, an exactly neutralized mixture con- 

 taining a few lethal doses of toxin is, of course, without action, 

 whereas a large bulk of the same mixture may be toxic ; this 

 also is readily explicable. Then there are some old experiments 

 of Buchner's, which showed that a mixture of tetanus toxin and 

 antitoxin which was neutral to mice would produce tetanus in 

 guinea-pigs, and several others (Roux's and Roux and Vaillard's) 

 of similar nature. The explanation of these is also easy. 



The most interesting explanation of a previously known phe- 

 nomenon which Madsen offers in the light of his new theory is 

 that of the immunization of animals by means of a neutral mixture 

 of toxin and antitoxin. If we follow Ehrlich, and believe that the 

 compound is a stable one, this is very difficult to explain. Madsen's 

 solution is that the mixture contains free toxin, to which the 

 immunizing property is due. 



Again, we can also explain the death of animals from specific 

 intoxication when it occurs in spite of the presence of free anti- 

 toxin in the blood in exactly the same way. It is true that the 

 free antitoxin would tend to inhibit dissociation ; but, on the other 

 hand, the hypersensitiveness of the tissues which occurs at the 

 early stages of the process of immunization and it must be 

 remembered that it is only in these stages that death from in- 

 toxication takes place would render the cells more susceptible 

 to minute amounts of toxin. The explanation may not be a 

 perfect one, but it appears to be the best forthcoming. 



The importance of the whole question from the point of view 

 of immunity rests on this question of the dissociability of the 

 combination, for it is obvious that if this is the case, our views of 

 the action of antitoxin in the animal body will be very different 

 from those we shall hold if we regard the toxin-antitoxin molecule 



