29 



In the next place it has been shown that " lytic substances " 

 produce variants which are similar, in many important respects, 

 to those occurring naturally or spontaneously in cultures and 

 sometimes in the animal body. It is known, for example, that the 

 effect of the lytic agent upon bacterial growth is to cause a culture 

 to split up into two types, the " sensitive," which is highly sus- 

 ceptible to the action of this agent and rapidly undergoes autolysis 

 under its influence, and the " resistant," i.e., a type which resists 

 this action. Here reference may be made to Gratia's work* on 

 the production of variants with the aid of lytic substances. 

 Starting with a single strain of B. coli, he obtained eleven different 

 forms, each with distinctive characteristics though all still retained 

 the specific properties of B. coli. In the course of this work, he 

 says, " our attention has been called repeatedly to similar facts 

 reported by Arkwright." He refers to Arkwright's observations 

 on " rough " and " smooth " variants which are discussed above 

 by F. Griffith and me (p. 5 and p. 25). 



Significance is to be attached to the fact that the initial 

 stimulus which produces transmissible " lytic substance " may be 

 derived from many quite different kinds of material, e.g., fsecal 

 extracts from healthy or diseased persons or from healthy animals 

 of various species, urine, diluted sewage, extracts of normal 

 organs, peritoneal exudates of guinea-pigs inoculated with some 

 bacterium, mixtures of bacterial culture and leucocytes, and so on. 

 It is of much interest to find that, whether the modification arises 

 " spontaneously " or under the influence of one or other of these 

 heterogeneous " lytic influences," the kinds of variants which are 

 produced are always very much the same. The reason, I think, 

 is that the modifying influence, whatever its nature, always acts 

 in the same sort of way, viz., by interfering with the normal 

 synthetic activities of bacterial protoplasm at the critical time 

 when the growing bacterium is about to subdivide. 



Something may now be said about the transmissible properties 

 of lytic substance, which, since they are of bacterial origin, will 

 naturally depend on the characters of the bacterial protoplasm 

 from which they were derived. 



Sometimes the individuality of the strain from which they 

 originated is marked very strongly. A good example is given by 

 Gratia. | He started with a lytic substance (bacterial filtrate) 

 which acted only on the particular strain of B. coli from which it 

 was derived. It was " without any action not only on other closely 

 " related species but also on other strains of Bacillus coli." 



He found, however, that he could make it produce a lytic 

 substance possessing a wider range of action. From his original 

 strain of B. coli he separated out two types, the " sensitive " and 

 the relatively " resistant," upon both of which his first lytic 

 filtrate produced lysis. With the filtrate from the lysed 

 " resistant " strain, " a very marked dissolution was observed of 



* Journ. Exper. Med., XXXV., p. 287, 1922. 

 t Journ. Exper. Med., XXIV., p. 115, 1921. 



