37§ PATHOGENIC BACTERIA. times contains them, so that the eruption may be regarded as one of the local irritative manifestations of the bacillus. The amount of local disturbance, in proportion to the constitutional disturbance, is, in the majority of cases, slight, and almost always partakes of a necrotic charac- ter, which suggests that in typhoid we have to do with a toxic bacterium whose disease-producing capacity resides in the elaboration of a toxic substance. This, indeed, is true, for Brieger and Frankel have separated from bouillon cultures a toxalbumin which they thought to be the specific poison. Klemperer and Levy also point out further clinical proof in certain exceptional cases dying with the typical picture of typhoid, yet without char- acteristic post-mortem lesions, the only confirmation of the diagnosis being the discovery of the bacilli in the spleen. Pfeiffer and Kolle found that the toxic substance resided only in the bodies of the bacilli, and could not, like the toxins of diphtheria and tetanus, be dissolved in the cul- ture-medium. This was an obstacle to their immuniza- tion-experiments as well as those of Loffler and Abel, later to be described, for the only method of immuniz- ing animals to large quantities of the bacilli was to make massive agar-agar cultures, scrape the bacilli from the surface, and distribute them through nutrient bouillon. When injected into guinea-pigs the typhotoxin of Brieger is productive of increased secretion of saliva, in- creased rapidity of respiration, diarrhea, and mydriasis, and usually causes a fatal termination in from twenty- four to forty-eight hours. As the discovery of the bacilli in the spleen, and espe- cially the securing of a pure culture of the bacilli from the spleen, are sometimes attended with considerable dif- ficulty because of the dissemination of the colonies throughout the organ, E. Frankel recommends that as soon as the organ is removed from the body it be wrapped in cloths wet with a solution of bichlorid of mercury and kept for three days in a warm room, in order that a con-