Genetic Analysis 273dominant to most mutated alleles of known genes which were at least partially re-
cessive. “Wild type” alleles were the ones selected to allow a buffered, more or less
constant activity even in the presence of disturbances in the internal or external
circumstances: “The degree of dominance [of the wild type allele] was probably
only a concomitant or reflection of the general degree of activity (‘potency’) of the
gene” and “lies in the protection thus afforded the individual against disturbing
genic and exogenic influences” (Muller [1935, 409-410], see also Muller [1950]).
However, to study the nature of the process of mutation proper, a quantitative
method was needed to measure mutation frequencies as function of varying a
controllable agent. Attempts to learn about the nature of mutations by artificially
inducing heat (and cold) shocks and similar treatments failed, because if they had
any mutagenic effects these were too weak to be amenable to quantitative genetic
analyses. Muller chose lethals as aclassof mutants that abolish essential functions
of genes (on the X-chromosome of Drosophila), thus providing an easy, unequivocal
test for detecting mutations in any of many genes. TheClBchromosome was a
specially designed trap for detecting lethal mutations in the fly’s X-chromosome
that allowed for the quantitative analysis of mutation induction [Muller, 1927b,
1928]. In 1927 Muller announced at the International Congress of Genetics in
Berlin that he induced mutations by irradiating the gonads of Drosophila with
intensive doses of X-rays [Muller, 1927a]. In the same year, Stadler showed that
ionizing irradiations of barley pollen induced mutations in progeny plants [Stadler,
1928].
The quantitative analysis indicated that gene mutations were induced propor-
tionally to the X-ray dose given to the spermatozoa of Drosophila flies, indepen-
dent of the intensity (dose/time) of the irradiation, and apparently without a
threshold dose. The induction of chromosomal aberration, on the other hand, was
related exponentially to the irradiation dose. Thus it was inferred that mutations
were single-hit events or “point mutations”; whereas aberrations required two in-
dependent single hit breaks (although the exponent was more like 3/2 than the
expected 2). These conclusions were further supported by the observation that
more “dense” ionization radiations, like those of neutrons, were highly efficient in
inducing aberrations.
The “target theory” successfully determined the dimensions of bacteria and
enzyme molecules from X-ray induced inactivation curves. The single-hit lethal-
mutations’ induction curve suggested the extension of the “target theory” to mea-
sure the dimensions of genes as if they were autonomous discrete (globular) entities
in the cellular broth [Timof ́eeff-Ressovskyet al., 1935]. This conception was re-
flected in Schr ̈odinger’s [1962] description of genes as “aperiodic crystals” and
mutations as “quantum jumps” of states of matter in his influentialWhat Is Life?
These estimates were, however, soon challenged when it was found that factors
like anoxia reduced the frequency of mutations and chromosome breaks induced by
a given dose of radiation. This meant that the radiation induced ionizations might
induce mutations or chromosome breaks not necessarily by direct hit of the “tar-
get” itself. The effective target of the radiation could be larger than the final gene-