I didn't even realize for years after I met Bill at a gathering of the Tennessee Citizens for Wilderness Planning he helped found that this light-hearted and gentle man was a famous scientist who turned his agile and funny brain to serious subjects—like estimating the genetic risk that people face following exposure to radiation and chemicals. My discovery of the "other Bill" came one day at his Watts Bar Lake cabin, a decade after Bill had retired and after I had joined the Russell group as a "young" graduate student.
passed the rainy afternoon explaining to me the "specific locus test," which
measures the frequency of transmitted gene mutations induced in mouse
cells that are ancestors of sperm. I was awed as I began to understand
the impact of the test and the creative thinking that Bill put into
I never lost the "first Bill," of course. How many Ph.D. celebration parties have included a Gilbert and Sullivan-style serenade written and sung by a member of the National Academy of Sciences?
In 1936 Bill earned his Ph.D. degree at the University of Chicago, under the famous population geneticist Sewall Wright, who helped Bill set the stringent scientific attitude and standards that were hallmarks of both Wright and Russell. From Chicago, Bill moved to the Jackson Laboratory in Bar Harbor, Maine, switched from guinea pigs to mice, and began his illustrious career. I never knew Tibby Russell, Bill's first wife, but have heard from others who did know her that she was as special as Lee is. Bill once told me, "I am unique; all my wives are members of the National Academy of Sciences."
Beginning in 1947, with Lee at this side, Bill organized and presided over the Mammalian Genetics Section of the Biology Division at ORNL. The section's initial goal was to explore the genetic hazards of radiation to humans. Earlier work in using fruit flies as the model organism had established a set of radiation genetics principles that were thought to be well understood and assumed to be universally applicable. Bill, however, conceived and developed the specific-locus test to measure both the biological and physical factors that influence mutation frequency in mammals. Experiments designed and overseen by Bill led to the first determination of how frequently X-rays induce mutations in mammals. These experiments led to a number of important discoveries. I've selected three discoveries that I consider most important, although several others could easily make the list.
First, he discovered that, compared to fruit flies, mammals are much more sensitive to radiation and much more likely to have radiation-induced mutations. This finding led to a lowering of the permissible radiation dose for humans. At the time, there was concern about radiation exposures of workers and the public because of fallout from atomic bomb tests, construction and operation of research reactors, and development of nuclear power.
Second, in one of those leaps of insight that only very open and agile minds can make, Bill realized that some reproductive cells in mammals must be able to repair genetic damage. His experiments showed that the mutation rate is lower when the dose is protracted over an interval of days or weeks , than when the same total dose is given all at once. This repair hypothesis proved to be very controversial. The finding led to acrimonious debate when Bill declared it, but he proved to be correct in the end.
Bill's way of thinking may have influenced Lee. She made these same leaps of logic in perceiving that cells in female mammals have only a single active X chromosome and that gender in mammals is determined by the presence or absence of the Y chromosome. She also spearheaded studies of irradiated mouse embryos that led to controls on the scheduling of X-ray exposure of potentially pregnant women.
The third of Bill's findings—that different mutagens cause different kinds of mutations—has proved important for research that continues to this day. Bill's discovery that the chemical ENU is the best mutagen for producing point mutations in mice has formed the basis for huge research programs currently supported by many sponsors interested in mouse models for human genetic diseases. ORNL conducts biological research using ENU. Millions of dollars a year are spent worldwide on genetics research using ENU.
For this body of work, which led to the realization that mutation frequency can be mitigated by repair of DNA damage caused by radiation, Bill was twice nominated for a Nobel Prize.
I could not give a précis of Bill's career at ORNL without including the famous trip that he and Gene Oakberg made in the 1950s to the site of an aboveground atomic bomb test. They stacked cages of mice in an old Ford and drove from ORNL to Nevada. Because they needed females in various stages of gestation, they had to check vaginal plugs (a sign of mating) along the way, sneak the mice into motels, and fill water bottles for the mice in bathroom sinks wherever they stopped. Once at the Nevada test site, they spent days practicing quick recovery of the cages from exposure chambers built into the desert floor. Obviously, the environment for both mice and scientists would be highly radioactive after the bomb test, so only a few minutes of whole-body exposure in getting the mice out of their cages could be tolerated. Bill and the mice returned to Oak Ridge on a DC3 airplane, arriving just in time to be accused of contaminating practically the whole city until it was realized that the fallout cloud had accompanied them home. The offspring of those mice carrying radiation-induced mutations from that Nevada experience are still in use in our research program.
Bill was also very interested in why genetically identical mice often show variable traits. He did some fascinating work transplanting ovaries, even from female fetuses, to see if the maternal environment might be responsible for some of the observed variations. His famous paper "Offspring from unborn mothers" was a report of this type of work. Lee has said that his extreme near-sightedness made the handling of the tiny embryonic ovaries easier for him than for most people.
During his career, Bill served on numerous national and international committees, and he was invited to give presentations all over the world. He won many awards, most notably the Roentgen Medal (jointly with Lee) and the Fermi Award, DOE's highest honor, which Lee also won years later. Such solemn occasions gave his light-hearted side an outlet. At a Fermi Award congratulatory dinner given by Union Carbide, ORNL's managing contractor then, he professed to being glad about the "economic savings for the company, because my wife is also my supervisor, and I presume she's invited in both capacities but can eat only one dinner."—Dabney Johnson
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