490 STUDIES IN IMMUNITY. 



duce pleural effusions, the whooping-cough toxin shows certain 

 analogies with diphtheria toxin. 



The most interesting observations, however, are furnished on 

 subcutaneous inoculation. Guinea-pigs that have received an injec- 

 tion under the skin of 0.5 and even 0.25 of a cubic centimeter of 

 endotoxin show a very marked edema, which frequently becomes 

 hemorrhagic at the point of inoculation; the surrounding area 

 rapidly takes a dark color without any tendency to suppuration. 

 A rapid extensive necrosis of the skin follows and breaks down, 

 leaving a large ulcer. This local effect is much more marked than 

 are the generalized symptoms on subcutaneous inoculation; in 

 horses, ulcers a decimeter square may be produced ; a marked wast- 

 ing is always noted. 



The demonstration of these properties in the whooping-cough 

 toxin seems to us to round out satisfactorily the ideas which we 

 previously had as regards the pathogenesis of whooping-cough. 

 The production by the bacillus of an extremely irritating poison 

 which is capable of producing necrosis of the epithelial lining of 

 the bronchi where the organism multiplies will explain the charac- 

 teristic symptoms of the disease and the appearance and persist- 

 ence of the violent accesses. 



The fact that whooping-cough is not generally a very serious 

 disease, in spite of the toxic power of the causative bacillus, is 

 easily understandable in view of the fact that the organism does 

 not tend to produce a generalized infection. 



The whooping-cough bacillus is unfortunately rather difficult 

 to handle on account of its remarkable instability on heating, which 

 prevents sterilizing it. The grinding up of the bacteria is neces- 

 sarily done in the open air, and it is impossible, therefore, to avoid 

 dust and consequently contamination of the toxin. Steriliza- 

 tion such as is employed to eliminate contaminating organisms 

 rapidly destroys our toxin, or at least weakens it very markedly. 

 On heating to 55 degrees for a short time the endotoxin solution 

 becomes opaque and almost inoffensive. 



The use of chloroform, toluol and thymol, which ordinarily arc 

 so useful in conserving toxins without harming them, weaken the 

 whooping-cough toxin very much, and render it almost useless. 

 We have been forced, therefore, to keep our bacilli ground with 



