In Pursuit of the Gene

X-RAYS © 227
C � B experiments and those in the earlier joint experiment. The mystery of
the high variability in the mutation rate required further investigation, and
as it would turn out, Muller’s attempts to resolve the inconsistencies in the
lethal mutation rate would consume the better part of the next six years.
As usual, Muller’s powerful imagination raced ahead of the experiments,
and despite the difficulties he was now completely convinced that
the study of the nature of mutation was a key to understanding the gene.
As he had done ten years earlier for complex traits, he was now prepared to
begin to lay the conceptual groundwork for a real mutation theory, which
he introduced in September 1921 at the Second International Congress on
Eugenics in New York City. “Beneath the imposing building called heredity
there has been a dingy basement called Mutation,” he dramatically introduced
his subject. “Lately the searchlight of genetic analysis has thrown a
flood of illumination into many of the dark recesses there.” 22 Several distinct
phenomena had been grouped together under the name of “mutation”
because they all involved the appearance of a new genetic type, he explained.
It was unfortunately now necessary to recognize that the results
with Oenothera, which had once formed “the backbone of the earlier mutation
theory,” as he put it, were no longer strictly relevant to the modern
problem. It was now time to replace the “elaborate system of conclusions”
derived from Oenothera and build a theory based on the study of changes in
the individual hereditary units.
Although he granted that almost nothing was known about the mechanism
of mutation or about the nature of the genes, other than that “they
behaved like material particles existing in the chromosomes,” it was possible
to begin to put down the basic outlines of a new theory of mutation.
More than a hundred examples of changes in individual genes had been
found in Drosophila, and these would provide the basis for the new theory.
The most important new principle, he asserted, gleaned from the quantitative
study of mutations conducted by Altenburg and himself, concerned
the relatively high stability of an individual gene. Even at the higher rate
found in their first summer at Woods Hole, Muller computed that a typical
gene underwent mutation no more frequently than once every 2,000
years. 23 A corollary of the stability of genes was the principle that external
agents could not in general be shown to significantly affect the rate of pro-