66 W. Howard Hughes 



drawn. If five or six single cells were picked the individual 

 populations derived from them would vary, occasionally 

 being more sensitive than the parent but usually being inter- 

 mediate between the parent and this most extreme example. 

 The apparent increase in resistance by even steps is here due 

 to selection having been made and is not an expression of any 

 law of variation. 



Cavalli-Sforza saw these results before they were completed 

 and pointed out that the pattern was that of a normally distri- 

 buted population curve rather than that of mutation as ordi- 

 narily understood (Cavalli-Sforza, personal communication). It 

 should be noticed that the sensitive moiety of the population is 

 killed off by the methods used and that there is no evidence from 

 this type of experiment of cells more sensitive than the parent. 



Yudkin considered this type of experiment on antibiotics 

 and his own work with flavin, and advanced his theory of 

 resistance (Yudkin, 1953). This is still the most likely 

 explanation of the work of the present author, and of that 

 of Eagle and his associates. No subsequent experiments have 

 thrown any serious doubt on it. 



Yudkin's theory postulates that when a cell divides, the 

 daughter cells will be unlike each other and unlike the parent 

 cell. Support for this hypothesis was provided by studies of the 

 behaviour of a strain of Escherichia coli B when grown under 

 conditions of diminished oxygen supply (Figs. 3-5). The 

 long organism was produced at the first division of the parent 

 cell, the sister cell gave a normal colony. This inability 

 to divide is frequently seen in fresh isolates of most rod- 

 shaped organisms. If these long cells are selected and sub- 

 cultured in broth and then a fresh test is made it will be found 

 that they form an increasingly large proportion of the entire 

 culture and strains can be bred composed of cells all of which are 

 sensitive to the environment. With this phenomenon in mind 

 the reactions of bacteria to antibiotics can be reconsidered.* 



* A film that illustrates and contrasts the action of penicillin and of a wide 

 spectrum antibiotic, in this case chloramphenicol, was shown at this point, 

 and can be obtained from the Photographic Department, St. Mary's Hospital, 

 London. 



