70 Infection 



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 

 been known since the early work of Brieger and Fraenkel 

 and Roux and Yersin. They seetn to be excretions of the 

 bacteria, which are not retained within the cells, but elimi- 

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

 appropriate bouillon cultures of the diphtheria bacillus, 

 the diphtheria 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 similar toxic 

 powers. The poison is most active where its diffusion is 

 most limited. 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, 



