History of Research on Chemical Mutagenesis

Abstract

The interest in mutation is as old as the modern science of genetics. It is well known that the term “mutation” was coined by de Vries for sudden hereditary changes in Oenothera; although we now realize that these changes were not mutations sensu stricto, the term has been retained. De Vries was also the first to dream of the induction of “directed mutations” that would provide man with “unlimited power over Nature.” This dream has been a major spur to the search for chemical mutagens. In 1914, T. H. Morgan reported on unsuccessful attempts to produce mutations in Drosophila by treatment with alcohol or ether. Mann, in 1923, likewise failed to obtain mutations from treatment of Drosophila with a variety of chemicals, including morphine, quinine, and a number of metal salts. During the 1920s, mutation research was put on a firm basis by H. J. Muller, who developed the concept of “mutation rate” and devised objective, efficient, and quantitative techniques for its measurement. These techniques proved their value first in the discovery and analysis of the mutagenic action of ionizing radiation, but they were soon applied also to tests of chemicals. Muller himself obtained negative results with several chemicals, but Russian workers (Lobashov, Saccharov, Magrzhikovskaya) claimed success for ammonia, iodine, potassium permanganate, and copper sulfate; for the last-named substance, confirmatory data were published by Law in the United States. Although in these experiments the differences between the frequencies of sex-linked lethals in control and treated flies were statistically significant, treatment effects were always small and rarely reached or exceeded 1% lethals. Since at that time the striking differences between spontaneous mutation frequencies in successive broods were not known, one cannot exclude the possibility that the effective treatments had acted simply by altering the rate of sperm utilization. It would be interesting to repeat some of these experiments with a rigorous brood pattern technique.