Modes of Bacterial Pathogenesis 71 



Wheeler,* Leach, f Mclntyre,{ and others, it seemed re- 

 markable that micro-organisms whose filtered cultures con- 

 tained little 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 quantities, 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 

 bacilli, and many supposedly harmless bacteria, contain 

 intensely active toxic substances. In all probability some 

 of the toxic substances 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 comminution of culture masses 

 made solid and brittle by exposure to liquid air, as suggested 

 by Macfadyen and Rowland; the autolytic digestion of bac- 

 teria 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 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, whose 

 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 reac- 

 tions of varying intensity result. 



The extracellular toxins, of which those of Bacillus 

 tetani and Bacillus diphtheriae can be taken as types, have 



*"Jour. Amer. Med. Assoc.," 1904, XLII, p. 1000. 



t Ibid., p. 1003. J Ibid., p. 1073. 



