In Pursuit of the Gene

X-RAYS © 223
through, due to the inexperience of the students, nonetheless the result
seemed to suggest that large numbers of flies would have to be examined to
find a rate for the appearance of new lethal mutations.
In the fall of 1918, Muller returned to Columbia, where he’d been offered
a temporary appointment as an instructor that he hoped would lead
to a permanent position, and his hunt for a mutation rate was put on hold.
Meanwhile, Altenburg, who had remained in Houston, took up the project,
counting lethals on the X chromosome using the more straightforward sex
ratio method. He began by breeding 90 females and counting the sex ratios
of their progeny, eliminating those flies that carried a preexisting lethal
mutation. Daughters from normal females were then bred and screened for
the presence of new lethals by the sex ratio test, and this process was repeated
for five generations. As expected, there were several ambiguous
cases, which were subjected to further tests, but when the uncertain cases
were resolved, Altenburg had found an astonishing 13 lethals in a total
number of 385 females tested, which was equivalent to a rate of 1 lethal in
every 60 X chromosomes. At this rate, an X chromosome would be expected
to accumulate one recessive lethal mutation every four years. Although
it was clear that humans could not possibly accumulate mutations
at the same rate, otherwise a girl would be likely to possess several X-linked
lethal mutations before she was of reproductive age and would therefore
be incapable of producing sons, nonetheless Altenburg’s result was mindboggling.
In the end, Altenburg’s simple and direct approach yielded the first
major breakthrough in mutation theory in thirty years, though the results
of his experiment so defied expectations and met with such skepticism
among other Drosophila workers that he did not rush to publish them. 8
Instead, he and Muller met the following summer at the Marine Biology
Lab at Woods Hole and undertook a joint experiment to verify Altenburg’s
initial findings. To avoid the uncertainty associated with the sex ratio test,
they followed the method Muller had invented for his undergraduate
class at Texas the previous year. At the same time they looked for an effect
of temperature on mutation rate by dividing the cultures into two
lots, one grown at 80°F. and the other, kept cool in shallow pans of