Seventy years ago: mutation becomes experimental.

I N 1927 H. J. MULLER (1890-1967) published in Science a paper entitled “Artificial Transmutation of the Gene.” It reported the first experimental production of mutations and opened a new era in genetics. The title is curious. Why transmutation rather than mutation? The answer emerges from another paper (MULLER 1928a), written in 1926. After reviewing the repeated failure of efforts by many workers to modify the mutation rate, MULLER asked the question: “Do the preceding results mean, then, that mutation is unique among biological processes in being itself outside the reach of modification or control,-that it occupies a position similar to that till recently characteristic of atomic transmutation in physical science, in being purely spontaneous, ‘from within,’ and not subject to influences commonly dealt with? Must it be beyond the range of our scientific tools?” MULLER thought of his radiation experiments as parallel to those of RUTHERFORD, only a few years earlier, demonstrating experimental transmutation of chemical elements. Like the physicists, who were attracting a great deal of public attention at the time, MULLER had tampered with a fundamental natural process and had succeeded in mastering it. He was an instant celebrity. The 1927 paper is also curious in another way, for it presented no data-no dosage measurements, no numbers, no statistical analysis. MULLER simply reported qualitative results and rough comparisons, e.g., a mutation-rate increase of “fifteen thousand percent.” But a paper without data invited skepticism, and the skeptics included no less than T. H. MORGAN, who was always suspicious of speculations and invariably asked for the data. MULLER’S idea was clearly to establish priority. He noted that many of the mutations were repeats of those found earlier. Most were recessive, but a few were dominant. Many were lethal or sterilizing, and there were dominant lethals, not easy to detect. In addition to gene mutations, MULLER reported a number of chromosome rearrangements, especially translocations. He suggested mutation as a cause of cancer. And in this, his first paper on the subject, he began his lifetime crusade