Mutations of Bacteria from Virus Sensitivity to Virus Resistance.

After the introduction of pure culture techniques for the study of bacteria in the late 19th century, it became accepted that bacteria, like higher organisms, have inherited qualities. A single bacterium isolated on the surface of agar produces a clone of descendants, all of which resemble the original parent in virtually every respect. However, it also became clear that variants appear in otherwise pure cultures and that these variants breed true. What was the origin of such variants? Despite the widespread recognition of the role of chance mutations in the genetic variation of higher organisms, bacteriologists were reluctant to extend this concept to bacteria. Bacterial cultures appeared to be plastic. Exposed to adverse environments, cultures quickly gave rise to genetically stable types adapted to the new conditions. The majority of bacteriologists in the early 20th century believed that environment directly induced some or all of the cells in the population to become stably adapted. Obviously the much faster rate of growth of bacteria than of higher organisms contributed to the appearance of plasticity. Various mechanisms other than mutation were proposed for these variations, including shifts in chemical equilibria by Hinshelwood (A. C. R. Dean and C. Hinshelwood, p. 21–45, in E. F. Davies and R. Davies [ed.], Adaptation in Microorganisms, Cambridge University Press, Cambridge, U.K., 1953). The absence of sexual differentiation and of a chromosome visible by light microscopy made it easier to accept a different mode of inheritance for bacteria. The phenomenon of induced enzyme biosynthesis, which had not been clarified at that time, lent circumstantial weight to the plasticity view. Against this background, the first clear-cut evidence for the occurrence of spontaneous mutation in bacteria was provided by Luria and Delbrück in 1943. They demonstrated that, when a sensitive culture is plated in the presence of an excess of bacteriophage T1, colonies arise from phage-resistant mutants, which were present in the inoculum before exposure to the phage. Luria and Delbrück used fluctuations in the fraction of resistant mutants across a series of cultures to argue that the phage-resistant mutants predated selection by the phage. The Luria-Delbrück paper took a solid first step toward showing that bacteria had genes like plants and animals. Luria and Delbrück were an effective team. They had agreed to study the problem of “secondary growth” (of the phage-resistant mutants) in April of 1941. However, the problem proved harder than expected. Early attempts to devise critical experiments were unsuccessful during Luria’s visit to Delbrück at Vanderbilt University in the fall term of 1942. However, Luria continued working on the problem at Indiana University, where he was an Assistant Professor. Luria, in Delbruck’s words, “. . . early in 1943 hit on a satisfactory method of deciding the issue. This method was worked out, the theory by me here at Vanderbilt, the experimental technique by Dr. Luria at Indiana.” Delbruck and Luria then went on to create a whole new school of phage genetic research. A. DALE KAISER