26 



animal's local lesion then acted as a culture tube in which the 

 bacillus was allowed to age. On plating after two months, he 

 obtained a mixture of (a) colonies and morphologically different 

 (b) colonies. When (6) was subcultured, it often threw off some 

 (a) colonies, " especially soon after it was first isolated." The 

 variant (6) " usually sedimented both in broth and saline " ; 

 it was inagglutinable and not agglutinogenic, but conferred active 

 immunity against both itself and (a) and was quite as pathogenic 

 as (a). 



The special point of interest in Mary Cowan's subdivision of 

 streptococci into " rough " and " smooth " strains is that the 

 former were much less pathogenic than the latter. 



To summarise the above, when the action of the spontaneous 

 modifying influence is prolonged, the following changes make their 

 appearance. The colonies formed by the variants are distinctive ; 

 there is more profound alteration in agglutinability and agglu- 

 tinogenic capacity; there is less tendency of the variants to 

 revert to the parent form, and, finally, there is loss of virulence. 



In a still more advanced stage of spontaneous modification 

 there is the production of lytic substance. 



Here are some examples. Bail* stated that on three occasions 



he had obtained lytic substance directly from three old cultures 



of Flexner's bacillus. Gildemeisterf declared that the presence 



of lytic agent could be demonstrated in a special type of colonies 



which he had described previously (1917) under the name of 



" inconstant forms " (Flatterformen). He gave them this name 



on account of their irregularity and their liablity to change in 



subculture. He was working with intestinal organisms belonging 



to the coli, dysentery, typhoid and paratyphoid groups and had 



isolated his cultures from faecal material. Otto and MunterJ 



also noted that the lytic principle could be obtained from old 



cultures (aged 3 weeks to 3 months) without the aid of the animal 



body. Gratia, § again, has obtained similar results by merely 



allowing a normal culture of B. coli to grow old. ' ' An old agar slant 



" of Bacillus coli shows an uniformly dull film on which appear 



" very distinctly, here and there, small vitreous colonies." These 



colonies produced a growth " which possesses a great resistance 



to the lytic agent," whereas the " dull film " was found to be dead. 



" At the same time we have had the good fortune to isolate 



from a subculture of the original strain a colony of organisms 



which are, on the other hand, extremely sensitive to the lytic 



agent." The two types grew differently in broth, and the 



sensitive type was also distinguished from the other by being 



non-motile and less virulent. Ledingham.|| after remarking that 



some strains of bacteria " show lytic changes normally," says : — 



I attach great importanc e to this fact. Dr. Lepper, at the 



* Wien. klin. Wochenschr., p. 447. 15th Sept., 1921. 

 t Berl. klin. Wochenschr., p. 1355. 14th Nov., 1921. 

 j Deutsch. med. Wochenschr., p. 1579. 29th Dec, 1921. 

 § Journ. Exper. Med., p. 115, 1921. 

 || British Med. Journ., p. 297. 19th Aug., 1922. 



