76 Infection 



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, 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 reactions of varying intensity result. 



The extracellular toxins, of which those of Bacillus tetani and 

 Bacillus diphtherise 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 

 the bacteria. Thus in culture filtrates of the tetanus bacillus there 

 are at least two very different active substances, the tetano-spasmin 

 that acts upon the nervous system with convulsive effect, and the 

 tetano-lysin that is solvent for erythrocytes. 



In all probability all of the culture filtrates of bacteria are highly 

 complex because of the addition of the various metabolic products 

 — toxins, lysins, enzymes, pigments, acids, etc. — of the bacteria, 

 as well as because of changes produced in the medium by the ab- 

 straction of those molecular constituents upon which the bacteria 

 have fed. This complexity makes it difficult to accurately study 

 the toxins, which we scarcely know apart from their associated 

 products. 



