NYTimes.com Article: Scientist at Work: Constantly in Motion,
Like DNA Itself
khare at alumni.caltech.edu
khare at alumni.caltech.edu
Thu Mar 4 11:36:58 PST 2004
This article from NYTimes.com
has been sent to you by khare at alumni.caltech.edu.
DNA checksums ?
Love the idea of pinging the molecule with an electron to see if it conducts at the right frequency to detect errors. Very cool...
khare at alumni.caltech.edu
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Scientist at Work: Constantly in Motion, Like DNA Itself
March 2, 2004
By NATALIE ANGIER
PASADENA, Calif. - Like many a bio-minded scientist in this
gilded age of the genome, Dr. Jacqueline K. Barton, a
professor of chemistry at the California Institute of
Technology here, considers the double helix so
aesthetically pleasing that she keeps a chubby, cheery
model of it smack in the middle of her office table.
The three-foot-high sculpturette of some 20 base pairs of
DNA - a tiny fraction of the 3 billion nucleic building
blocks that make up the human genome - has a sort of Henry
Moore bulbosity to it, coupled with the graceful, emergent
torque of the Venus de Milo. All very sinusoidal and
maternal: just what one would expect of the famed Molecule
of Life and the mother of all cookbooks.
Yet as Dr. Barton speaks of her studies about how DNA might
keep itself fit and fiery by shooting electrons up and down
its span, the familiar object on her table begins to evoke
a very different image: that of a lightning bolt, a
crackling zigzag of opportunity. Far from being a
couch-bound custodian of information, it seems, the
molecule of life is the original live wire.
"What many people don't realize is how dynamic the
structure of DNA is," said Dr. Barton, her fingers
fluttering lightly over the model. "The base pairs are
always moving and vibrating, electrons are migrating, holes
are opening up and closing through the center of the DNA."
It's like a cocktail party or a kindergarten class, she
said. "Nothing stays still for more than a femtosecond here
or a millisecond there."
Yet for all the squirm and spark, DNA, the ultimate source
of information on how cells and bodies should behave,
remains a remarkably stable presence throughout one's
terrestrial tenure, and even beyond. It's because the
molecule is so substantive and slow to degrade, said Dr.
Barton, "that you can still look at dinosaur DNA."
Dr. Barton, 51, and her colleagues are seeking to
understand just how the double helix manages to be at once
so twitchy and so reliable, capable of constant interchange
with tens of thousands of proteins and other small
characters in the cell, hammered at by blistering
chemicals, ultraviolet rays and corrosive free radicals,
and expected to split and split and split again, spawning
numberless generations of daughter DNA molecules in the
course of cell division; and all the while still staying
sane and functional and relatively error-free.
Dr. Barton proposes that the DNA molecule polices itself
electronically, periodically delivering a flow of charged
particles from Point A to Point B to check for mutant,
misplaced bases that might be skulking in the corridors. If
the electrons proceed unimpeded, she suggests, all is well.
But if there is a kink in the sequence, the smallest sign
of a nascent mutation, the flow would short-circuit. That
break would in turn sound an alarm, alerting the cell's DNA
repair crew to fix the mess now, or at least sometime
The work is part of Dr. Barton's larger exploration of the
electrical properties of DNA, and how the trafficking of
charged particles in and around its zigs, swags and
crevasses may help mold the contours of the master
macro-molecule or set its timbre twanging.
Dr. Barton is a heavy-metal fan. She and her lab mates have
created metal-studded molecular probes that allow them to
generate electrons when and where they want them, and to
follow the migration of the particles as they ping their
way through DNA. By taking an electron's eye view of the
double helix, she hopes to help solve a mystery of
molecular biology: how all the tens of thousands of tiny
proteins responsible for servicing the genome and carrying
out its encoded directives find their correct genetic
targets along an otherwise forbidding spaghetti of
On a practical note, Dr. Barton has designed tiny
metal-based probes to test the integrity of a given DNA
sample as quickly and cheaply as possible. A company that
she founded in San Diego, GeneOhm Sciences Inc., is now
working to translate some of her ideas into a simple
laboratory assay that could detect disease mutations in a
patient's DNA by simply running a current through it and
seeing if anything trips it up.
Such a procedure would be much simpler than using
biochemical methods to spell out, or sequence, thousands of
DNA subunits in search of the occasional miscreant. Her
work is also attracting attention from experts in the
fashionable field of nanotechnology, the science of the
extremely tiny, who would dearly love to exploit nature's
microcircuitry in devices of their own.
Dr. Barton has long been a high-wattage figure on the
chemistry circuit. She is a MacArthur fellow, a member of
the National Academy of Sciences and a winner of laurels
from the National Science Foundation, the American Chemical
Society and the American Philosophical Society, to name a
Like the molecule she studies, Dr. Barton is a braid of
contradictions: animated and composed, optimistic and
pragmatic, genial and driven. "If the house were to burn
down, if things were going badly in the lab, if a paper
wasn't accepted by the right journal, she wouldn't get
angry or frustrated or wear it on her sleeve, the way I
might," said Dr. Peter Dervan, 58, her husband and also a
professor of chemistry at Caltech.
Dr. Barton is compact, dark-eyed, dark-haired, and, true to
her New York roots, she likes dressing in black. She walks
briskly, as nearly all scientists do, but with a decided
bounce in her step. "What can I say?" said Dr. Robert G.
Shulman, an emeritus professor of molecular biophysics and
biochemistry at Yale. "We were all jealous of her husband
when they got married."
As one of the very few women ranking as a full professor at
Caltech, and in the chemistry trade generally, Dr. Barton
has perhaps inevitably become a role model to young women
in science. Later this month, for example, she is
participating in the first Rosalind Franklin International
Lecture Program at the Imperial College in Britain, devised
"to expose young scientists" to that wondrous sight,
"internationally recognized women scientists."
Dr. Shana Kelley, an assistant professor of chemistry at
Boston College, said, "I tell people she's found out how to
do it all, that you don't have to choose between career or
family, and that's what I want for myself."
"I might have had more doubts if I hadn't watched her," she
Dr. Anna Marie Pyle, a professor of molecular biophysics
and biochemistry at Yale who studied under Dr. Barton,
said: "Jackie conveys to her students the importance of
creativity and imagination in science. Women need to have
somebody express confidence in their creative abilities,
not just their ability to work harder."
The good life has its grindstones and metronomes, though.
The couple's time is so tightly scheduled, admitted Dr.
Dervan, "that I can tell you where we'll be to the day, to
the hour, for the next 12 months."
When they are at work, they work, and when they are at
home, they are parents. (They have two children -
Elizabeth, 13, and Andrew, 21, Dr. Dervan's son from his
"People assume that because Peter and I are both chemists,
we talk all the time about chemistry," said Dr. Barton. "In
fact, we almost never talk shop. If we go out to dinner
together, we talk about Elizabeth."
They travel often for work, but they are zealously
efficient in those jaunts. Dr. Barton has been known to fly
back and forth to Europe in a single day, alighting abroad
just long enough to deliver a two-hour talk. "Who wants to
sleep in a hotel alone," she said, "when you can sleep at
home with your family?"
One of the few things that gets her ever so wryly ruffled
is the public's attitude toward her beloved discipline,
chemistry. "People hear the word `chemical' and they
automatically think it's bad," she said. "Even my daughter,
when she was in kindergarten, came home and said she'd
learned that there were too many chemicals in the world. I
told her, Elizabeth, we're all chemicals! Everything is
made of chemicals!"
Dr. Barton is also skeptical whenever laypeople tell her
they "flunked chemistry" in high school. "Not everybody
could possibly have flunked chemistry," she said. "Surely
someone somewhere got a B."
For that matter, she said, why do people so readily confess
to their complete ignorance of chemistry and other science,
even to the point of sounding boastful? "People are
perfectly willing to say to me at a party, I haven't the
foggiest idea what you're talking about, which they would
never do if we were discussing current events," she said.
"Why aren't they embarrassed? Why don't they think, Gee,
maybe this is something I ought to know a little bit
about?" Fear is no excuse. For all its daunting reputation,
she said: "Science really isn't that hard. I don't think
it's more difficult than anything else."
Born and raised in New York City, she attended the
Riverdale Country School for Girls. Back then, she said,
"young girls didn't take chemistry."
The first chemistry course she took was in college, at
Barnard. It became her major; she graduated summa cum
laude. She earned her Ph.D. in inorganic chemistry from
Columbia, and did a postdoctoral fellowship at Bell Labs
and Yale. Dr. Barton then took a position as assistant
professor of chemistry at Hunter College in New York.
She soon moved to Columbia, where her research using metal
ions to study DNA began attracting considerable attention,
from her future husband, among others. She and Dr. Dervan
knew each other for years professionally before they began
dating, and when Caltech sought to woo Dr. Barton from
Columbia, she told the recruiters of the potentially
confounding fact that she was in love with a member of
their faculty. "Their response was, well, that's further
incentive for you to come here," Dr. Dervan said.
Soon after moving to Caltech, Dr. Barton gave birth to her
daughter, and within short order learned of her MacArthur
"genius" award. "That came at a good time for me," she
said. "I was wondering if people might think, oh, she's a
mother now, is she going to start slowing down? The
MacArthur gave me the reassurance that I was probably O.K.,
and that I could go on to do interesting stuff."
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