November 28, 1902.] 



SCIENCE. 



857 



in the right direction has already been 

 opened, and, if I mistake not, its further 

 pursuit is most promising of valuable re- 

 sults in the near future. 



Consider by way of illustration how 

 helpless we now are in our efforts to ex- 

 plain the characteristic lesions of typhoid 

 fever on the basis of our knowledge of the 

 properties of the typhoid bacillus. That 

 these lesions are referable to the action of 

 toxins cannot, I think, be seriously ques- 

 tioned. Especially from the investigations 

 of Mallory, we know that the most charac- 

 teristic histological changes of this disease 

 consist in the proliferation of the reticular 

 or so-called endothelial cells of the lym- 

 phatic tissue of the intestine and the 

 mesenteric glands and of similar cells in 

 the splenic pulp, and in the assumption by 

 these proliferated cells of remarkable pha- 

 gocytic activities towards the lymphocytes 

 in the former situations and towards the 

 red corpuscles in the spleen. Mallory be- 

 lieves that these changes are best inter- 

 preted by supposing that the typhoid toxin 

 directly stimulates to proliferation the 

 endothelial cells, which then devour their 

 offspring, the lymphocytes, and the red 

 corpuscles. 



I have suggested as another explanation 

 that the typhoid bacillus produces a lym- 

 phocytotoxin and a hemolysin, and that 

 the proliferation of the fixed cells is partly 

 compensatory and partly for the increased 

 production of macrophages. We already 

 know that this bacillus generates a hjemo- 

 ljd;ic agent, and we also know that one of 

 the effects of injection of hemolysins is 

 to increase greatly the number of macro- 

 phages containing red corpuscles in the 

 spleen. 



Through the kindness of Professor Flex- 

 ner I have had the opportunity of study- 

 ing the extraordinary changes produced 

 in all the lymphatic glands and in the bone 

 marrow of rabbits by injections of lympho- 



toxic or myelotoxic serum obtained by 

 treating a goose with lymphatic or marrow- 

 tissue of the rabbit. One of the most 

 striking effects of this poison for lympho- 

 cytes and other leucocytes is the very ex- 

 tensive proliferation of the reticulum cells 

 in the lymphatic nodes and of the marrow 

 cells. In the light of these observations 

 it is clear that a positive demonstration 

 of the production of a lymphotoxin by the 

 typhoid bacillus would materially advance 

 our understanding of the morbid anatomy 

 of typhoid fever. Another lesion of this 

 disease, only second in importance to those 

 mentioned, is the occurrence of plugging 

 of the small vessels. Dr. Fisher, in my 

 laboratory, has recently shown that such 

 thromboses are produced by the experi- 

 mental inoculation of rabbits with the 

 typhoid bacillus. I have already pointed 

 out that many of these plugs are agglutina- 

 tive thi'ombi. 



Of course infectious diseases other than 

 typhoid fever could also be cited, did time 

 permit, as equally forcible illustrations of 

 the aid which pathology may reasonably 

 expect from more precise knowledge of the 

 bacterial cellular poisons. It is probable 

 that siieh knowledge will lead to improve- 

 ments in the quality for therapeutical pur- 

 poses of the so-called bacteriolytic serums, 

 some of which, as now prepared, are not 

 so wholly devoid of antitoxic properties as 

 is often represented. We may also antici- 

 pate from investigations of the character 

 indicated much light upon one of the most 

 puzzling of bacteriological problems — the 

 localization of bacteria in disease. Toxic 

 lesions and the plugging of small blood 

 vessels are certainly often of decisive in- 

 fluence in determining this localization, as 

 has been demonstrated especially for the 

 staphylococcus pysmias by Muscatello and 

 Ottaviano.* 



* Muscatello and Ottaviano, Virclww's Archiv, 

 1901, CLXVI., p. 212. 



