20 A. C. R. Dean and Sir Cyril Hinshelwood 



(c) When colonies are formed in such examples as the growth 

 of Bact coli mutabile on lactose or Bact. lactis aerogenes on 

 D-arabinose, the primary colony has often become so large 

 before any of the secondaries appear that to attribute all the 

 utilization of the adaptation-requiring substrate to these is 

 impossible. Moreover, re-spreading of inocula taken from 

 primaries and papillae on lactose-endo-agar plates may result 

 in nearly as many Lac"*" colonies from the former as from the 

 latter. In general, however, the papillae should yield more 

 thoroughly adapted cells since they have utilized lactose after 

 the lag required for the adaptation, whereas parts of the 

 primary grew on peptone, and had no opportunity for using 

 lactose (Dean and Hinshelwood, 1957). 



Fluctuation Tests 



The belief that the Luria and Delbriick fluctuation test is a 

 reliable proof of the spontaneous origin of drug-resistant 

 mutants or of mutants capable of utilizing new substrates is 

 now less widely held than formerly. Factors other than 

 mutation, which are not usually controlled rigidly in the test, 

 have been shown to be capable of producing the observed 

 variation between samples from the same culture and samples 

 from different cultures. It has also been questioned whether 

 Newcombe's spreading technique provides unambiguous 

 evidence for the existence of spontaneous mutants and 

 whether the results of the fluctuation test are necessarily 

 strengthened by the inclusion of a test for correlation between 

 relatives or by invoking the Lea-Coulson distribution (Dean 

 and Hinshelwood, 1952a and b; Hinshelwood, 1953; Dean, 

 1955). 



The Technique of Replica Plating and Related 

 Methods 



The natural level of resistance of bacteria to drugs differs 

 among varieties of the same strain and among closely related 



