A potential hazard: explosive production of mutations by induction of mutators.

A systematic study of the genes that control mutation rates began about five years ago both in prokaryotic and eukaryotic organisms. Before this, mutator mutants generally were regarded as freaks, causing their mutagenicity possibly by the build-up of a product of intermediary metabolism which was a mutagen. The concept of differences in the spontaneous mutation rate as a natural phenomenon was suggested by Ives (1) in 1950, but it was not until 1962 that mutation rate enhancement was recognized as a natural component of the meiotic process by Magni and von Borstel (2). In 1966, defective DNA polymerase was noted to have mutator activity (3), and in the following two years defective enzymes associated with DNA repair were implicated in a large variety of organisms (4). Still, the isolation and identification of mutator mutants were difficult at best, although Liberfarb and Bryson (5) were able to isolate a number in E. coli. Cox and his collaborators (6) have been studying these and other mutators in E. coli, and Drake (7) has been examining likely candidates for mutator activity among genes encoding known biochemical functions in the bacteriophage T4. Mutator mutants were induced and selected in the yeast Saccharomyces (8). The unex-