48 THE SCIENTIST | the-scientist.com
PROFILEa more complex organism in which to study developmental
biology. For her postdoc, she moved across the Atlantic
to Cambridge, England, to work at the MRC Laboratory
of Molecular Biology. There, she joined the lab of Sydney
Brenner, a biologist who later would win the Nobel Prize for
his groundbreaking work on C. elegans.
Meyer chose to study the nematode because she was drawn by
the question of how its sex is determined. “I was fascinated again
by a binary developmental decision,” Meyer says. “It was the same
idea [as with the lambda phage], but on a much huger scale.”
Jonathan Hodgkin, a nematode biologist who had been
a graduate student in Brenner’s lab, had already identified a
mutation that caused genetic males to become hermaphrodites,
and vice versa. But Meyer wasn’t convinced that this mutation
explained the sex switch, because there had been hints from
previous research that the switch might be linked to dosage
compensation of X-linked genes. To o much or too little X
expression is lethal, so “I thought I couldn’t just look for sex
reversal, because the animal I’m looking for might be dead,”
Meyer explains.
Years earlier, biologists Victor Nigon and Robert Herman had
shown that C. elegans embryos were sensitive to the number of
X chromosomes relative to sets of non-sex chromosomes called
autosomes in their genomes. By studying animals that carried
two, three, and four sets of autosomes, they discovered that
worms born with an X chromosome:autosome ratio between 0.5
and 0.67 would be male, while ratios between 0.75 and 1 would be
hermaphrodites. (Other ratios would either be lethal or impossible
to generate.) There had also been work by Thomas Cline, a
geneticist who was then at Princeton University, that revealed
a link between sex determination and dosage compensation in
fruit flies.
Meyer decided to work backwards in the worms, screening for
genes that were involved in dosage compensation. Eventually she
found autosomal genes that, when disrupted by mutation, led to
abnormal levels of X-chromosome expression (Cell, 47:871–81, 1986).
“Barbara is a brilliant and creative scientist,” says Cynthia
Kenyon, the vice president of Calico, a San Francisco-based
biotech company. Kenyon, who met Meyer while the two were
both graduate students at Harvard in the 1970s, says that Meyer
will “stop at nothing to figure out how to dissect a system of
incredible complexity.”
Meyer continued her work on C. elegans at MIT in
Cambridge, Massachusetts, where she started a professorship
in the early 1980s. Anne Villeneuve, a Stanford University
geneticist who was one of Meyer’s first graduate students at
MIT, says she was inspired by Meyer’s boldness in the early
days of her lab. “She had to have confidence in the system that
she was building from scratch, and she had to believe that it
was going to work out,” Villeneuve says. “Once it was built,
everyone could see how cool it was.”
Her worm system led to the drain-dumping-turned-eureka
moment, as well as to many other important insights into themolecular machinery involved both in dosage compensation and
in other fundamental cellular processes, such as meiosis.A BRUSH WITH FAT E
During Meyer’s early days of working onC. elegans, Princeton’s
Cline was but a faceless author on papers she’d read with great
interest. She was amazed by the quality of the manuscripts, and
because he was the only author on many of them, she suspected
that he must have had a long career in academia—and thus was
many decades older than her.
Meyer later learned that this was not the case: Cline was, in
fact, only a few years her senior. The two met for the first time at a
developmental biology conference in 1981 and bonded over their
shared scientific interests. They started dating several years later,
in 1986, and once their romance began, things moved quickly—
within a month of getting together, they were married. “I fell in
love with him from reading his papers,” Meyer says.
When the couple got married, they were professors in different
states: Cline was in New Jersey, and Meyer in Massachusetts.
Cline, like Meyer, was from California, and he wanted to return.
Although Meyer loved MIT and the fast-paced lifestyle of the East
Coast, managing her father’s health care from across the country
was proving to be a challenge. After her father had a heart attack,
Meyer and Cline moved back to their home state, where they both
obtained faculty positions at Berkeley.
One of the defining features of the couple’s now decades-long
relationship has been a common passion for science. Together,
they have coauthored a handful of review articles, and to this
d ay, they edit each other’s papers. “We’re each other’s best
critics,” Meyer says. The two also share a love of hiking and have
trekked along numerous, sometimes-treacherous trails around
the world.
On one evening outing with Cline on Costa Rica’s Osa
Peninsula in 1999, Meyer took a wrong step in the dark
and fell off a 12-foot-high cliff. She landed on her back and
shattered her ankle, but she considers herself lucky: there was
a block of concrete right by her head, and iron rods jutting
out from the space between her legs. “It makes me realize
that anything can happen at any moment, and you better
live your life well,” she says. “It made me think really hard
about what could happen in the future—so I’m very good at
troubleshooting in advance.”
That preparedness has served Meyer well both inside and
outside of the lab. Throughout her career, she has juggled many
tasks, from running her lab and mentoring countless students
to organizing scientific meetings and serving on numerous
advisory boards for universities, professional societies, and
both governmental and nonprofit organizations. And, she’s still
determined to crack more scientific mysteries—for example, to
further unravel the biochemical mechanisms underlying dosage
compensation and to understand how chromosome structure
affects gene expression.
“There are quite number of big questions left,” she says. g