46 THE SCIENTIST | the-scientist.com
PROFILEDEBORAH STALFORDT
he tiny, transparent wormCaenorhabditis elegans can be
born either as a male, typically with one X chromosome, or
as a hermaphrodite, with two. When Barbara Meyer began
a professorship at MIT in the 1980s, she wanted to pinpoint the
genetic pathway that determined the worm’s sexual fate. There
was evidence that this process was tied to dosage compensation,
a delicate balancing act that ensures X-chromosome expression is
matched between the two forms—a condition necessary for sur-
vival not only in worms, but also in humans, fruit flies, and other
animals in which one sex carries two X chromosomes, while the
other carries only one.
Meyer suspected that the gene responsible would control
the levels of X chromosome expression in only one form of the
worm—either it would limit expression in XX C. elegans, or it
would boost expression in individuals with only a single X—and
failure to do so would result in the animal’s death. Her team,
however, struggled to find such a gene. Then, one d ay, a “eureka
moment” almost got thrown down the drain.
In one experiment, her team was growing hermaphrodites
with a mutation in a sex-specific gene they knew was involved in
X dosage compensation. At first, as expected, the nematodes were
growing poorly and dying, but then a lab technician noticed that
they suddenly looked healthy and started multiplying. Thinking
that there was a problem with the culture, he started to discard the
samples in the sink. From across the room, Meyer shouted, “Stop!”
She suspected that those healthy worms might contain the
answer to her question, and she was right. There had been a
spontaneous mutation in what turned out to be the master sex-
switch gene, responsible for both determining sex and repressing
the expression of X chromosomes in hermaphroditic worms (Cell,
48:25–37, 1987). “In that [culture], through serendipity, was the
long-sought-after gene that I wanted,” Meyer says.AN UNEXPECTED PAT H
Growing up in Stockton, a small city in California’s Central
Valley, in the 1950s, Meyer never thought she’d become a scientist.
She was fascinated by the sciences, which she encountered both
through interactions with an uncle who was an aeronautical
engineer and via a wide selection of nonfiction books. But when
asked in high school to write an essay about what she envisioned
as her future career, Meyer wrote that she would become a
medical lab tech. “[I wasn’t] even dreaming that I’d be able to
have a PhD,” Meyer recalls. In her town, “there was no model for
being a scientist... certainly not for a girl.”Meyer longed to escape Stockton, which she describes as
a rather isolated place. She imagined traveling the world like
another of her uncles, a globetrotter who would visit with exotic
gifts from faraway places. She got her first travel opportunity after
she was accepted into Stanford University, which allowed her to
study abroad. She spent a semester at the Stanford campus in
Stuttgart, West Germany, in 1969. On one of her visits to Berlin,
where the infamous wall split the city in two, Meyer remembers
encountering a distressing sight: soldiers shooting at people who
were trying to escape across the border into the West. “When you
see these kinds of things, it makes you happier thinking about
science because there’s some logic to it, rather than watching
people get shot,” Meyer says. “That compelled me even more [to
go into science].”
After completing her undergraduate studies, Meyer joined
the lab of David Clayton, a developmental biologist at Stanford’s
California campus. There, she used herpes simplex virus and
mouse mitochondria to investigate a nucleotide-forming enzyme
called thymidine kinase. “That convinced me that I really wanted
to do [research],” she says. “Whether I could or not was another
question, but I really wanted it.”
While working in Clayton’s lab, Meyer decided she wanted to
pursue medical research and applied to medical school. During
the application process, several interviewers told her that they
saw her more as a researcher than a physician, or that if they
offered her a position in a medical program, she would simply
get married, pregnant, and drop out, Meyer recalls. She was
ultimately rejected.
That was a demoralizing experience, she says, but it turned
out for the best. She had also applied to graduate school, and soon
after her med school rejections, she learned she’d been accepted
into a program at the University of California, Berkeley—where
she would not only earn her PhD, but eventually go on to become
a leader in the study of genetic switches.A FATEFUL SWITCH
In graduate school, Meyer focused on viruses that infect
bacteria. One such bacteriophage, the famous lambda phage, can
live one of two lifestyles: a peaceful one, where it stays dormant
in a host’s DNA, or a violent one, where it hijacks the host’s
cellular machinery to replicate, then releases its progeny into the
environment.
When Meyer started at Berkeley, she was intrigued by the
factors that influenced how the lambda phage ended up onUniversity of California, Berkeley molecular biologist Barbara Meyer’s work with bacteriophages and
nematodes exposed the role of genetic switches in early development.BY DIANA KWONSwitch Master