RESISTANCE OF BACTERIA 225 



not produce indol. This third strain, as a matter of fact, aside from its 

 fermentation reactions, .changes a neutral red medium to a canary 

 yellow, coagulates milk, reddens litmus milk very strongly, but does not 

 produce indol, 



Fejgin has isolated similar strains from the stools of patients, showing 

 particularly the same agglutinative characters. 



This work is of the greatest interest, but it is not a question of the 

 possibility of isolating three strains from a mixed Shiga-bacteriophage 

 culture; there are thousands. All of the characters of the Shiga species 

 (and it is the same for any bacterium whatever) form, one might say, a 

 "puzzle" of which each of the fragments represents a character capable 

 of varying from zero to infinity. The character "glucose fermentation" 

 may be zero or it may be an energetic fermentation with gas, or it may 

 be an intermediate stage. The "agglutinability" character may be 

 anywhere from zero to a titre of 1 : 50,000, or even higher. The charac- 

 ter "toxicity" may lie anj^where between zero and a high potency. The 

 character "form" extends from coccus to bacillus. And the same 

 possibility for variation exists with respect to each character. But 

 experiment shows that through the influence of the bacteriophage, each 

 of these characters may be changed independently of the others. Con- 

 sequently the number of possible mutations is, in reality, unlimited, and 

 although the tendency for certain changes is undoubtedly far greater 

 than for others, it seems that a very great many are possible. 



It may be added, with reference to the staphylococcus, that when a 

 mixed culture, grown out at a temperature of 40°C. in spite of the pres- 

 ence of a bacteriophage of maximum activity, is planted in gelatin no 

 liquefaction occurs. From this it appears that a staphylococcus with 

 a maximum resistance no longer secretes a proteolytic enzyme. In 

 addition the capacity to produce pigment is lost. 



Biologists who have not kept in touch with the new facts disclosed by 

 our knowledge of bacteriophagy may well be astonished at these state- 

 ments, and they may even remain somewhat skeptical. But the experi- 

 mental procedure is so extremely simple that they can readily become 

 convinced of the truth of all these statements. Moreover, a deeper 

 study of these mutations is sure to completely revise our present concept 

 of the fixity of species. 



In summary, then, the most important fact to be derived from all of 

 these studies is that, exposed to the action of the bacteriophage, bacteria 

 undergo mutations, usually unstable ones, but that these may become 

 fixed under conditions as yet undetermined. These mutations are asso- 

 ciated with a state of resistance acquired by the bacteria. 



