90 Chapter 3. The molecular dance[[Student version, December 8, 2002]]
Figure 3.15:(Experimental data.) Some of Timof ́eeff’s original data on X-ray mutagenesis. Cultures of fruit flies
were exposed either to gamma rays (solid circles) or to X-rays (crosses). In each case the total radiation dose is given
in “r”units, with 1rcorresponding to 2· 1012 ion pairs created percm^3 of tissue. The vertical axis is the fraction
of cultures developing a particular mutant fly (in this case one with abnormal eye color). Both kinds of radiation
proved equally effective when their doses were measured in “r”units. [From (Timof ́eeff-Ressovskyet al.,1935).]
In 1927 he had found that exposure to X-rays could induce mutations in fruit flies. ThisX-ray
mutagenesisoccured at a much greater rate than natural, or spontaneous, mutation. Muller
enthusiastically urged the application of modern physics ideas to analyze genes, even going so far
as to call for a new science of “gene physics.”
Working in Berlin with the geneticist Nicolai Timof ́eeff, Muller learned how to make precise
quantitative studies of the frequency of mutations at different radiation doses. Remarkably, they and
others found that in many instancesthe rate at which a specific mutation occurred rose linearly with
the total X-ray dosegiven to the sample. It made no difference whether the dose was administered
gradually, or all at once. This simple linear law persisted over a wide range of doses (Figure 3.15).
Thus doubling the dose simply doubled the number of mutants in a given culture. Prior exposure
to radiation had no effect whatever on those individuals not mutated (or killed outright), neither
weakening nor toughening them to further exposure.
Timof ́eeff went on to find an even more remarkable regularity in his data:Allkinds of radiation
proved equivalentfor inducing mutations. More precisely, the radiation from X-ray tubes at various
voltages, and even gamma rays from nuclear radioactivity, all generated mutation at the same
rate per dose, provided that the dose was expressed by quoting the number of electrically charged
molecules (orions)per volume produced by the exposure (Figure 3.15).^8
Atthis point a young physicist named Max Delbr ̈uck entered the scene. Delbr ̈uck had arrived
in the physics world just a few years too late to participate in the feverish discovery days of
quantum mechanics. His 1929 thesis nevertheless gave him a thorough understanding of the recently
discovered theory of the chemical bond, an understanding that experimentalists like Muller and
Timof ́eeff needed. Updated slightly, Delbr ̈uck’s analysis of the two facts above ran as follows.
(^8) The “r,” or “roentgen,” units used in Figure 3.15 are now considered obsolete. The SI unit of radiation dose is
the gray (equal tocoul·kg−^1 and abbreviatedGy); one roentgen equals approximately 0.009Gy.