Inheritance in Single Bacterial Cells 71 



any rate for 4 hours, in a strength 20 per cent above that 

 which had originally been used. At the present rate of pro- 

 gress it will require about 40 subcultures to double the 

 resistance of the strain, but the number of cells being ex- 

 amined at each level is from 100 to 300 only. 



It appears that the transition from sensitivity to resistance 

 can be made gradually by very large numbers of small steps 

 made possible by the organisms differing from one another 

 just as do the units in any other population. 



REFERENCES 



Demerec, M. (1948). J. Bad., 56, 63. 



Eagle, H., Fleisciiman, R., and Levy, M. (1952). J. BacL, 63, 623. 



Hughes, W. H. (1952). J. gen. Microbiol., 6, 175. 



Hughes, W. H. (1955«)- J- gen. Microbiol., 12, 265. 



Hughes, W. H. (19556). J. gen. Microbiol., 12, 269. 



Mayr-Harting, a. (1955). J. gen. Microbiol., 13, 9. 



YuDKiN. J. (1953). Nature, Lond., Ill, 541. 



DISCUSSION 



Siocker: Dr. Hughes' approach is, I beUeve, a very valuable one. In 

 micromanipulation experiments, one is confined to examining small 

 populations. This means that one can only observe frequent mutations. 

 One is apt to think of spontaneous mutations as being very infrequent 

 events; but in bacteria, in regard to certain quantal or all-or-none 

 changes, there are a number of examples of spontaneous changes of 

 heritable character at rates of the order of IO-2 or 10-^ per bacterium 

 per generation. In most cases no analysis has been made to see whether 

 or not these changes result from changes of chromosomal genes. In 

 Salmonella, spontaneous changes of flagellar antigenic phase occur in 

 each direction at about this rate ; and this change has been shown to be 

 in fact something occurring at a chromosomal gene (Lederberg, J., and 

 lino, T. (1956). Genetics, 41, 743). Hughes' demonstration of heritable 

 differences in antibiotic sensitivity between two cells picked at random 

 from the same population is formally analogous to the differences in 

 antigenic phase which one may find between two Salmonella colonies 

 obtained by plating out a single colony; and might, like it, result from a 

 'change of state ' at a chromosomal locus. 



Hughes has examined cells of a single clone grown in a common 

 environment, and has shown that even a pair of sister cells may differ in 

 their ability to grow in a particular antibiotic concentration. Until a 

 direct test has been made one should not assume that such differences 

 are due to differences in the genetic constitution of the cells concerned, 



