Pathogenesis 91 



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 

 been known since the early work of Brieger and Fraenkel 

 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 less diffusible agar-agar. 



The soluble toxin is but one of numerous metabolic prod- 

 ucts 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 abstraction of those molecular con- 

 stituents upon wh'ich the bacteria have fed. This com- 

 plexity makes it difficult to accurately study the toxins, 

 which we scarcely know apart from their associated products. 



The chemic nature of the toxins differs. Undoubtedly 

 some are tox-albumins, but others are of different composi- 

 tion and fail to give the reactions belonging to the compounds 

 of this group. 



The variations observed in toxicogenesis under experi- 

 mental conditions in the test-tube indicate that similar 

 variations occur in the bodies of animals, and a few experi- 

 ments conducted with slight variations in the composition 

 and reaction of the media in which the bacteria grow will 



