Introduction xvii 



Litman and Pardee had found (104), is highly mutagenic in bacterial viruses. 

 Benzer and Freese's investigation, presented in this collection, showed that 

 the set of mutants induced by the action of 5-bromouracil is completely 

 different from the set of spontaneous mutants in the same general region of 

 the viral genome, demonstrating that "the mutagen does not merely enhance 

 the over-all mutation rate, but acts at specific locations in the hereditary struc- 

 ture." Mutational spectra of other chemical mutagens were subsequently 

 established, and it turned out that each of these substances raises the proba- 

 bility of mutation at a restricted number and individually characteristic set of 

 sites (27, 57). Further insight into the chemical nature of the induced muta- 

 tions was provided by studies that determined the connection between the 

 induction of a mutation at a specific site by a given mutagen and the ability of 

 the same, or of another mutagen, to revert this mutation to the original state. 

 On the basis of these results, Freese proposed that there exist two basic types 

 of point mutation in the viral genetic material: transversions, corresponding to 

 the substitution of a purine by a pyrimidine residue, or vice versa, and transi- 

 tions, corresponding to the replacement of one type of pyrimidine by the other 

 or of one type of purine by the other ( 56 ) . 



Not long after the discovery of the bacteriophage it was found that ultra- 

 violet light (UV) kills the virus particle (65), and since then, UV has been 

 the inactivation agent whose effects have been most extensively studied ( 136, 

 95, 110, 139). This work has shown that in addition to simply destroying the 

 reproductive power, UV also produces a number of important physiological 

 and genetic effects. The inactivated phages, furthermore, are by no means 

 inert, being still capable of adsorbing to and killing bacteria, and of interfer- 

 ing with the growth of other, unirradiated phages in the same host cell (111). 

 Some of the lethal effects of UV, finally, are reversible under appropriate con- 

 ditions. An important example of such reversibility is the existence of photo- 

 reactivation, discovered by Dulbecco (49) in the work presented herein. Dul- 

 becco found that viability is restored to UV-inactivated phages if bacteria 

 infected with such "dead" particles are illuminated with visible light. Dul- 

 becco's quantitative analysis of photoreactivation showed that a fraction of 

 the UV lesions, the photoreactivable sector, is restored by a light-activated 

 enzyme system of the bacterial host cell. Later work by Bowen (23, 24) 

 revealed that photoreactivation consists of two steps: the first step is a dark 

 reaction requiring no light, which generates the substances adsorbing and 

 "activated" by the quanta of visible light for the second, actually reactivating 

 step. Experiments by Lennox, Luria, and Benzer (99) suggested that photo- 

 reactivation constitutes a direct reversal rather than a bypass mechanism of the 

 primary ultraviolet damage, a conclusion that now seems certain since Good- 

 gal, Rupert, and Herriot demonstrated the in vitro photoreactivation of UV- 

 inactivated transforming DNA by illuminated bacterial extracts (61). 



Viability can also be restored to UV-inactivated phages if two or more 

 "dead" particles, each unable to reproduce itself in solo, happen to infect 



