CHAPTER III. 

 EVOLUTION OF THE INFECTIOUS DISEASES. 



DIPHTHERIA. 



WHEN one injects a non-fatal, but at the same time, a 

 highly pathogenic dose of diphtheria toxin under the skin of 

 a guinea-pig one sees a large edema develop at the site of 

 injection four to six hours afterward. From this edema and 

 at this time, almost all the injected toxin, can be extracted. 

 The edematous fluid injected into a second guinea-pig will 

 produce the same effect as the toxin injected into the first. 

 After a maximum development which is reached at the third 

 day, the edema is resorbed little by little and finally disappears 

 at the end of fifteen to twenty days. The quantity of toxin 

 which may be extracted diminishes at the same time. 



When this edema is allowed to develop normally we will 

 find from the center to the periphery every degree of reaction 

 which toxin can produce on the cellular tissues of the guinea- 

 pig. At the center the most concentrated solution will 

 destroy the cells; there will be necrosis of the epidermis and 

 even of the dermis and the area will be marked by an eschar ; 

 at the periphery where the limit is marked by pallor, the 

 tissue will appear normal. When we try to produce the 

 Schick reaction at the site occupied by the edema after the 

 complete subsidence of the latter, we find that the zone 

 limited by the pallor neutralizes more of the toxin than the 

 central part formerly occupied by the eschar and more than 

 every other part of the animal's skin. The center of the 

 area previously occupied by edema will give a positive reac- 

 tion to a dose which gives a negative reaction on the per- 

 iphery. That is to say, there is a local immunity at the site 

 of the injection of the toxin and this immunity is most 

 marked at the site which has suffered least by the injection. 



