48 EVOLUTION OF THE INFECTIOUS DISEASES 



minous than a non-fatal dose. A dose fatal in thirty-six to 

 forty-eight hours will not produce edema at all. We must 

 assume first that the cellular tissue can retain only a maximum 

 of toxin beyond which the excess will be fixed by other tis- 

 sues more vital to the life of the animal and second, that this 

 general reaction of nervous origin influences the local reaction 

 by diminishing the fixation capacity of the cutaneous cellular 

 tissue. 



There is no doubt but that all these reactions depend upon 

 physicochemical affinities and if we do not know the exact 

 mechanism we can at least say for the present that toxins 

 as well as antitoxins are colloidal substances, are aggregates 

 of molecules of varying size, and as seen in the ultramicro- 

 scope are spherical in form. We know that when causing toxins 

 and antitoxins to dialyze across collodion or gelatin mem- 

 branes of greater or less density, toxins pass easier than anti- 

 toxins, from which we can conclude that toxins form aggre- 

 gates less voluminous than antitoxins. The recognition of 

 these facts is sufficient for the moment to explain the curious 

 properties of mixtures of toxins with their antitoxins which 

 we have noted above. 



In a rabbit treated by diphtheria toxin, the phenomena 

 observed are quite different from those in the guinea-pig. 

 Hypodermic injections provoke only a little redness at the 

 point of inoculation and if the dose is not speedily fatal the 

 rabbit succumbs almost always some weeks afterward to a 

 cachexia accompanied by nervous disturbances. In this 

 animal, the toxin is not retained in the cellular tissue, but 

 passes to the nervous tissue and produces disturbances which 

 are relatively much more severe. The same result may be 

 obtained in the guinea-pig by injecting a mixture of toxin and 

 antitoxin containing a slight excess of toxin or of toxin fixed 

 en surcharge. In this case the toxin fixed by antitoxin (in 

 vitro) is retained to a less extent by cellular tissue; it diffuses 

 into other regions of the organism and may produce in the 

 guinea-pig the same cachectic state and the same nervous 

 disturbances as toxin of itself produces in the rabbit. 



The susceptibility of man seems to be intermediary between 

 that of the guinea-pig and that of the rabbit. In man toxin 



