82 Infection 



seemed remarkable that micro-organisms whose filtered cultures 

 contained httle demonstrable toxic substance are sometimes able 

 to produce active pathogenic effects. By means of special apparatus 

 in which the micro-organisms could be cultivated in enormous quan- 

 tities, and the disintegration of the micro-organismal masses secured 

 by subjecting them to high temperatures, to the action of mineral 

 acids or autolysis, it was discovered that the colon bacilli, typhoid 

 bacilH, and many supposedly harmless bacteria contain intensely 

 active toxic substances. In all probabiUty some of the toxic sub- 

 stances produced by such means are artefacts, but enough work 

 has been done to prove that insoluble toxic substances are present 

 in such organisms, and the toxic substances obtained by the com- 

 minution of culture masses made solid and brittle by exposure to 

 liquid air, as suggested by Macfadyen and Rowland; the autolytic 

 digestion of bacteria washed free of -their culture fluids and suspended 

 in physiological salt solution, and the dissolution of bacteria by 

 bacteriolytic animal juices clearly prove that endotoxins exist. 



It seems probable that there is considerable difference in the 

 readiness with which these intracellular toxic substances are given 

 up by the bacteria. From some they seem never to be set free in . 

 the bodies of animals into which the bacteria are injected; thus^ 

 Bacillus prodigiosus is usually harmless for animals, no matter what 

 quantity is injected, yet active toxic substances can be extracted 

 from the bodies of these organisms by appropriate chemical means. 

 From others they are given off in small quantities either during the 

 life of the organism or at the moment of death and dissolution, 

 as in the case of the typhoid bacillus and streptococci, whosfe filtered 

 cultures are almost harmless, though both organisms are pathogenic. 



The intracellular toxins are limited in action by the distribution 

 of the bacteria producing them. When these organisms are but 

 slightly invasive, more or less local reaction is produced; when they 

 are actively invasive, general reactions of varying intensity result. 



The extracellular toxins, of which those of Bacillus tetani and 

 Bacillus diphtheriab can be taken as types, have been known since 

 the early work of Brieger and Frankel and Roux and Yersin. They 

 seem to be excretions of the bacteria, not retained in the cells, but 

 eliminated from them as rapidly as they are formed. Thus, in 

 appropriate bouillon cultures of the diphtheria bacillus, the toxin 

 is present in large quantity and is highly virulent, but if the fluid be 

 removed from the bacteria by porcelain filtration and the remaining 

 bacilli carefully washed, their bodies are found to be devoid of 

 toxic powers. The poison is most concentrated where its diffusion 

 is most restricted, thus, agar-agar cultures of the tetanus bacillus 

 are much more toxic than bouillon cultures because the soluble 

 principle readily diffuses through the fluid, but is held by the agar- 

 agar. 



The soluble toxin is but one of numerous metabolic products of 



