MUTATIONS OF BACTERIA FROM VIRUS SENSITIVITY 

 TO VIRUS RESISTANCE 12 



S. E. LURIA» and M. DELBRtJCK 



Indiana University, Bloomington, Indiana, and 

 Vanderbilt University, Nashville, Tennessee 



Received May 29, 1943 

 INTRODUCTION 



WHEN a pure bacterial culture is attacked by a bacterial virus, the cul- 

 ture will clear after a few hours due to destruction of the sensitive cells 

 by the virus. However, after further incubation for a few hours, or sometimes 

 days, the culture will often become turbid again, due to the growth of a bac- 

 terial variant which is resistant to the action of the virus. This variant can be 

 isolated and freed from the virus and will in many cases retain its resistance 

 to the action of the virus even if subcultured through many generations in the 

 absence of the virus. While the sensitive strain adsorbed the virus readily, the 

 resistant variant will generally not show any affinity to it. 



The resistant bacterial variants appear readily in cultures grown from a 

 single cell. They were, therefore, certainly not present when the culture was 

 started. Their resistance is generally rather specific. It does not extend to 

 viruses that are found to differ by other criteria from the strain in whose pres- 

 ence the resistant culture developed. The variant may differ from the original 

 strain in morphological or metabolic characteristics, or in serological type or in 

 colony type. Most often, however, no such correlated changes are apparent, 

 and the variant may be distinguished from the original strain only by its re- 

 sistance to the inciting strain of virus. 



The nature of these variants and the manner in which they originate have 

 been discussed by many authors, and numerous attempts have been made to 

 correlate the phenomenon with other instances of bacterial variation. 



The net effect of the addition of virus consists of the appearance of a vari- 

 ant strain, characterized by a new stable character— namely, resistance to the 

 inciting virus. The situation has often been expressed by saying that bacterial 

 viruses are powerful "dissociating agents." While this expression summarizes 

 adequately the net effect, it must not be taken to imply anything about the 

 mechanism by which the result is brought about. A moment's reflection will 

 show that there are greatly differing mechanisms which might produce the 

 same end result. 



D'Herelle (1926) and many other investigators believed that the virus 

 by direct action induced the resistant variants. Gratia (1921), Burnet (1929), 

 and others, on the other hand, believed that the resistant bacterial variants 

 are produced by mutation in the culture prior to the addition of virus. The 



1 Theory by M. D., experiments by S. E. L. 



* Aided by grants from the Dazian Foundation for Medical Research and from the 

 Rockefeller Foundation. 



1 Fellow of the Guggenheim Foundation. 



[Reprinted by permission from Genetics 28: 491-511, November, 1943] 



