MARY-CLAIRE KING IS gone from her lab.
Which means the stereo is cranked up, Tom Petty and NPR
bouncing off glass beakers, floating above tiny vials of
breast-tumor DNA, wafting past stacks of manila envelopes that hold
the teeth and blood of children kidnapped and villagers massacred in
places far away.
King is a molecular genetics superstar – a leading scientist in
human genetics, breast-cancer research and international human
rights, so she is often gone from her University of Washington lab:
giving ideas, getting ideas, rounding up funding to cover her lab’s
$1 million-a-year operating costs.
The week before last, for example, she chatted with
philosophers at a theological union in Berkeley about how women with
breast cancer in their families can use genetic information to gain
a little more control over their lives, how international
human-rights workers can use genetics to redress past wrongs. Last
week she cartwheeled from Boston to Washington, D.C., to North
Carolina discussing molecular biology with grad students. Next week,
she’ll be in France.
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Sometimes, King is just down the street at the Fred Hutchinson
Cancer Research Center, chatting about dog genetics or holding a
How-to-Survive seminar for women assistant professors. Or she’s
across the lake with billionaire Paul Allen, discussing the
possibility of a “Nova” public television series on evolution. Or
breezing through the Rotunda cafeteria, shirt-sleeving biotech
wizard Leroy Hood as he munches a sausage and sauerkraut roll.
“Lee,” she says. “We’re on our way! We’ll have the materials for the
chip experiment in a couple weeks.”
King’s lab is on the first floor of the newly built K-Wing at
UW, the public university that tops the nation in federal research
dollars. A magnet for some of the hottest minds – and biggest money
– in biotechnology and cancer research, the K-Wing neighborhood has
become a national center for genetics research turbo-charged by
biotech tools. There’s a major academic medical center next door,
several research hospitals around town and a few high-powered labs a
short pedal down the Burke-Gilman bicycle trail.
The “Athens of Genetics,” King calls Seattle, citing the
critical mass of top thinkers, casual cosmopolitan city, snow-capped
mountains, sparkling water and relaxed atmosphere for bouncing
around ideas. It’s why she moved her lab here three years ago, after
three decades at the University of California at Berkeley.
The King Lab feels something like a commercial kitchen, minus
the grease: clinking glassware, stainless-steel sinks, cluttered
counters, small plastic funnels, large cardboard boxes, unusual
liquids, expensive electrical appliances.
A beige metal box the same size as a bread-baking machine can
whip up millions of copies of a selected gene before lunch. An
oven-size sequencer uses a laser and fluorescent dyes to display
snippets of DNA in a code of rainbow stripes resembling a tidy
Even more than equipment, the King Lab is people. Twenty-three
at last count. Average age, 28. Above-average education: nine
Ph.D.s, six doctoral students, a doctor, somebody tackling both
medical and doctoral degrees, seven undergrads, two technicians, a
genetics counselor, a coordinator. At Tuesday morning lab meetings,
they look like a multicultural Gap ad. They are fluent in Spanish,
French, Hebrew, Mandarin, Cantonese, Korean and German. They
Rollerblade to work. They sleep on futons. They have young children.
They play WhirlyBall on weekends. They drop King at the airport,
then borrow her Toyota to camp in the Olympics.
When King is gone, they blast Eric Clapton and Stone Temple
Pilots while sifting through family trees and pipetting 1/50th of a
drop of something into a teensy bit of something else.
At any given moment, each researcher is grappling with one
small experiment, hoping its outcome will give clues about a
slightly larger piece of the puzzle, and so on, until eventually,
everything adds together to answer a big question:
How and why do normal breast cells become cancerous? Which
genes are responsible?
Who were the children kidnapped during an army raid on an El
Salvador village 18 years ago? Is their father the peasant bean
farmer who has been searching for his sons and daughters so long?
MICHELE HARVEY smashes the streaked yellow molar with a $9.98
hammer from Ace Hardware. Four quick thumps and it shatters into
caramel shards, having been frozen overnight to 80 degrees below
zero. She spritzes the hammer head with bleach, dons a new pair of
gloves and goes onto the next tooth, someone killed in Bosnia,
Rwanda, Guatemala . . . a brother, an aunt, a husband . . . dead,
missing, but who?
The 31-year-old Canadian post-doc is recovering from jet lag.
She was in Port-au-Prince last week explaining mitochondrial DNA to
Haitian legal experts and collecting blood samples from people whose
relatives disappeared during the military dictatorship. The
villagers came in what must have been their best dresses, black
polyester on such a hot day. There were long lines, barely enough
juice drinks. Harvey pricked finger after finger with a sterile
lancet, and listened to each story. At some point, she says, all the
stories everywhere in the world overlap: . . . Then the paramilitary
troops came in and shot people like crazy . . .
Harvey is glad to be back in K-Wing, in the comforting routine
of the lab. Today she is extracting mitochondrial DNA from tooth and
blood samples, hoping to match missing people with their relatives.
Mitochondrial DNA is passed from mother to child. Everybody has it,
and virtually each maternal line has a unique pattern, like a
genetic family crest. If two people have the same crest, there’s a
greater than 99-percent chance they are maternally related.
In some cases, international courts use this evidence to answer
a fundamental question – Who was really killed? – as they prosecute
war crimes. Some families get closure when DNA tests shows a
relative really was in a mass grave. Other samples help reunite
families and return identities to young survivors who were kidnapped
as infants when their parents were murdered.
The King Lab does the most international human-rights work in
the world. The lab does not charge; typically, communities with
these sorts of human-rights abuses have little money. (King and
Harvey scrabble together about $100,000 a year in grants from the
International Commission on Missing Persons and humanitarian aid
In a pantry-size room across from the main lab, Harvey prepares
a gel that will help her “read” the DNA samples, so she can give
each unidentified person a unique genetic identity. She kneads foil
pouches resembling frosting mix and squirts the clear goo between
two glass panes, where it rises like a moon, then a mountain range,
and finally fills the horizon. She injects a micro-drop of
fluorescent cherry dye into each tiny vial containing DNA, taps some
numbers on the Macintosh keyboard and preheats the oven-size
Harvey’s work is driven by sophisticated science and savage
killings, so it’s startling to watch her use familiar household
items to do her experiments: tinfoil, plastic wrap, masking tape,
Styrofoam. Harvey uses an old-fashioned rectangular razor blade to
slit open her mail: forensic samples sent from all over the world.
“It’s not so much individual cases I get emotional about,”
Harvey says. “It’s the big mass graves that come in, 250 people
dead, and samples from their living relatives, and I’m going through
the list . . . mother, mother, mother, sister, brother and on and
on. It’s just crazy.”
She recalls the cardboard box from Bosnia, about the size of
two soda cartons. Inside were brown paper sacks, like Safeway
grocery bags, top edges folded down. The bags were filled with
little brown envelopes, each containing a tooth or piece of bone.
There’s a common understanding in forensic anthropology that each
tooth and every bone has a voice, a story to tell.
“When you open the box, it’s like this chorus shouting at you
that something terrible has happened, something unfathomable,”
Harvey says. “So I opened the box and shut it and left. Because it
was too much of a huge statement.”
By now, the sequencer is warm and ready to go. Harvey injects
29 samples of DNA between the glass plates. They drip through the
gel in pink columns the width of toothpicks. Each pink strip is a
person. This batch contains people from the Philippines, Argentina,
Croatia, Ethiopia and El Salvador.
The El Salvador samples came with a case report and a letter
from a father. The report tells about five children, all younger
than 6, who disappeared from a farming village in 1981 when it was
invaded by the 4th Infantry Brigade. Their mother had hidden with
her children in a hole. Soldiers shot her moments after taking her
baby daughter from her arms.
Case workers believe they have traced several of the children
to adopted families in America and Europe, where they are now
teenagers and young adults. Harvey crouches over the $100,000
sequencer. She is surrounded by the lab’s cool fluorescent lights
and angular instruments, but in her mind, she can see the lush dark
leaves of the village, the fields of pineapple and beans. She
imagines the father wearing a straw farmer’s hat. He has been
searching for his children for a long time. He does not mean to
disrupt their lives, but he wants to them know he never forgot them.
Greetings from your father to his beloved daughters and son . .
. I’ve always kept you in my mind, and I love you all very much. God
allowed me to find you . . . I want to tell you that if you all
decide to come to this country, El Salvador, you’re welcomed with
arms opened wide.
The letter will be forwarded if the results show a match
between their maternal uncle, whose DNA now seeps through the gel,
and the children, who are expected to give blood samples soon.
Harvey clamps the sequencer shut. It will be several hours before
she has results.
THE PLAN OF ALL plans, when it comes to living things, is DNA.
Think of human DNA, or deoxyribonucleic acid, as a cookbook, a
long spiraling list of 80,000 recipes arranged in 23 chapters. The
recipes, or genes, are instructions to make proteins that do
everything: digest food, re-grow little hairs in the inner ear, halt
the production of malformed cells.
Even though the recipes use only four ingredients – chemicals
called A, C, T and G – the cookbook is hard to decipher because: 1)
Each recipe is a long string of A’s, C’s, T’s and G’s in thousands
of precisely ordered combinations. 2) The recipes are in teeny tiny
type and not fully indexed. 3) Gobs of extra ingredients are
sprinkled between the recipes, making it hard to know what’s recipe
and what’s just gob.
The goal of the federal Human Genome Project is to catalog and
completely define all the recipes. The King Lab works from another
direction. They identify a genetically related disease and then try
to figure out what went wrong in the genes. Which of the 80,000
recipes got smudged? And which of the thousands of ingredients in
the recipe is lost, extra or in the wrong order?
It is an enormous puzzle coiled inside a tiny cell.
King has loved solving puzzles since she was a small girl
playing number games by her father’s bedside in suburban Chicago. He
was troubled by blood clots and Parkinson’s disease from the time
she was a toddler, so instead of tossing balls in the yard, they’d
juggle elaborate story problems about horseshoes and long country
roads. He never finished college, but loved math.
King majored in math at Carleton College before tackling
genetics at UC Berkeley. Her graduate-school mentor, the late Allan
Wilson, taught her how to break down complex problems into small
testable questions. Her Ph.D. thesis, showing that humans and
chimpanzees share more than 99 percent identical genes, was
published on the cover of the prestigious journal Science.
From population genetics and evolution, she leaped to
epidemiology, human genetics and molecular biology. Thirty years
ago, King says, women weren’t expected to accomplish much in her
field, so she had the freedom to create her own path and take a lot
of risks. The scientist says she was forced to master clear
efficient thinking so as not to waste time when she became a single
mom when her daughter, Emily, was 5. Back then, the secret to doing
a lot of important things, King says, was to eliminate everything
superfluous: chatting, most events involving food, time off.
Besides, she says, “It’s false economy to think you can’t think or
do more than one thing at once.”
This summer, King plans to go on her first vacation in 18
years, a boat trip with friends up Alaska’s Inside Passage.
Over the years, despite long days in the lab and at home, King
never forgot the rest of the world. At Berkeley, during the Vietnam
War, she helped organize 30,000 voters to write letters protesting
America’s bombing of Cambodia. Soon after, she began using genetics
research to reunite Argentinian grandmothers with infants stolen by
the junta during the eight-year “Dirty War.” It became a lifelong
cause, and she adapted a mitochondrial DNA sequencing technique to
identify people in human-rights cases where there aren’t many
In 23 years, King and her lab have churned out more than 200
academic papers, some of the research quite splashy. Her lab has
identified two of the seven genes that cause hereditary deafness.
Her researchers have worked on AIDS, lupus and rheumatoid arthritis.
“The intensity is good and bad,” says Eric Lynch, a 31-year-old
research assistant professor who identified the deafness genes. “She
has unbelievable energy . . . weekends, evenings in the lab. It’s
hard to keep up . . . She’ll let you know, in a nice way, if you’re
not meeting expectations.”
King says her lab self-selects. “People come to this lab
because they want to get something done.”
King drew the most fame, along with intense competition, in
1990, when she linked familial breast cancer to a single gene –
after almost two decades of slogging with minimal funding past
skeptics’ raised eyebrows. Her discovery launched scientists around
the world on a mad sprint to clone the breast-cancer gene, a task
akin to searching for a car key dropped on the bottom of Lake
Washington. King lost the race to competitors in 1994.
She conceded none of her ardor for breast-cancer research, and
it remains her lab’s dominant project. Her competence as a scientist
and prominence as a proponent of cancer research have brought
several honors, including a $60,000-a-year lifetime grant from Walt
Disney’s family. Most colleagues offer nothing but praise for King.
But a few are jealous. And like all top researchers, she is haunted
by ancient academic feuds. King says she’s glad she didn’t know how
competitive the field would become when she started in it.
THE KING LAB moves at a steady marathoner’s pace, day by day, drop
by drop, everyone trying to get something done, hopefully before “Em
Cee” (an affectionate nickname that refers both to Mary-Claire’s
initials and her charisma as master of ceremonies) calls between
flights or gets back to the lab.
When King is in, the stereo snaps off. It is replaced by the
scientist’s musical laughter, her chorus of questions, her hunger
for results. At 52, King is a dynamic presence, mind leaping, hands
gesturing, smile dimpling, pencil twiddling, tawny hair bobbing like
pony’s mane as she nods excitedly and exclaims, “Really? That’s
She clicks through the bays, a swirl of energy that lures
people from their lab benches and computer screens. It seems as if
something exciting is about to happen, as if all the pieces will
zoom together . . . into a breakthrough! A discovery! A cure!
Actually, despite the billions of dollars poured into human
genetics research in recent decades, the field has produced only a
handful of cures, mostly for rare diseases.
Finding a “cure,” to geneticists, is sort of like preventing a
potential landslide by figuring out which rock, or gene, would
trigger the tumble, and then stabilizing that rock to prevent
disaster. So far, it’s been easier to find trigger rocks than to
stabilize them. Scientist have identified about 800 “damaged” genes
linked to disease. Yet instead of providing easy solutions, this
knowledge has generated hard questions: Can an insurance company
refuse to cover someone who is likely to get a disease? Does a
scientist who identifies a gene own rights to it? What to do if you
learn you have an 80-percent chance of getting breast cancer – but
there’s no cure?
King is determined to close the gap between predicting who will
have a disease and doing something about it. When she speaks at
cancer-research benefits, she looks out at the banquet hall and sees
both the problem . . . We’re all at high risk for breast cancer . .
. and the solution . . . We can all work together . . . “Our goal is
to eliminate breast cancer as a cause of death,” she declares. “It
is never soon enough.”
Curing cancer may seem an arrogant ambition – until you
consider the accelerated pace of research in King’s field. Less than
a decade ago, it took scientists two weeks to type a genetic marker
(a sort of bookmark that helps locate genes). Now it takes only a
few hours. Five years ago, a sequencer could screen only 50 people’s
DNA at a pass. Now it can test 500. There are still endless samples
to pipette, glassware to wash, infinite printouts of the letters
A-C-T-G, but the new technology has eliminated much of the waiting
in lab work.
Upstairs in K-Wing, Leroy Hood’s molecular biotech lab has
helped develop a silica microchip the size of a thumbnail that
compares thousands of genes with thousands of other genes – in less
than a day. The King Lab will use tools like this to find out what’s
happening to the genes – which rocks trigger landslides – when
normal breast cells turn cancerous.
“If this works, I’ll buy lattes for a week!” King tells a
gaggle of grad students and post-docs who have spontaneously
gathered next to the journal table and paper cutter to toss around
For the experiment, the King Lab needs two types of breast
tissue, normal and tumor, each sample about the size of a pencil
eraser. Both bits must come from the same woman. And since RNA
spoils fast once it leaves the body, somebody from the lab needs to
be in the operating room to put the tissue on ice. King turns to
Heather Mefford, the doctor-to-be working on her Ph.D., who skated
to lab this morning. “Would you be willing to scrub?”
“Ummm,” Mefford says.
“Excellent!” King says.
HEATHER MEFFORD hurries to Operating Room No. 7 from K-Wing through
a labyrinth of hallways and stairs, past the aroma of Chinese
take-out at the nurses’ station. By the time she changes into blue
scrubs, surgeon Ben Anderson is deep in pre-op banter with his
. . . Mary-Claire King’s the one who said: Hey, wait a minute,
there must be a genetic link in all these families who have breast
cancer. And everybody else said: Naaah . . ..
Two weeks earlier, King had met with Anderson and another UW
surgeon to request breast tissue. Anderson was intrigued by King’s
new experiment because it focuses on genes in non-inherited breast
cancer. Even though 90 percent of women who get breast cancer don’t
have a family history of the disease, most of King’s previous
research has looked at the few damaged genes identified in inherited
breast cancer because it’s an easier target.
About the time King met with Anderson, 53-year-old Judy
Gearheart was having trouble falling asleep in the foothills of
Yakima. She tossed in bed, her skin hot and itchy. She scratched.
She felt a lump. It was malignant, and Gearheart had no family
history of breast cancer.
Two weeks later, at 3 a.m., she and her family climbed in the
car and drove across the Cascades. They parked at UW Medical Center
in time for noon surgery. Earlier, at Anderson’s request, Gearheart
had agreed to donate tissue to King’s research.
During surgery, Mefford waited with an ice bucket and
centrifuge tubes just steps away from where Gearheart’s brown braid
dangled off the operating table. Anderson carefully teased apart
gobs of pencil yellow fat and layers of tissue stained turquoise and
purple. The probe zinged when it neared radioactive tracer. The
suction wheezed. The cauterizer sizzled. After three hours, Anderson
cut out a meaty slab that surrounded the hard lump and sealed it in
a Ziploc bag. Before closing the cavity, he also extracted a bit of
normal tissue a good distance from the tumor site.
By the time Gearheart’s anesthesia wore off, Mefford was back
in K-Wing under a whirring lab hood, scalpel in each hand, mincing
the pale pearly bits into even tinier flecks. She bathed the tissue
in yellow antibiotic fluid and then a pink solution to help the
In a few weeks, after collecting tissue from several other
women, she told King, she’d know whether they’d have enough cells to
begin comparing tumor genes with normal genes.
“Terrific” King told her. “Sounds like a plan!
GENETICS IS the study of families, of information passed from
generation to generation through strands of DNA. King considers her
lab to be a family. She wants to pass on to them a method of asking
questions, tools to find the answers, a core set of values, an
excitement about research.
What’s exciting, King says, is that “You design the puzzle. You
can try to track down answers that are important to you. To me, the
most interesting questions are those that have potentially a very
Whether it’s bombing in Cambodia, kidnapped children in
Argentina or a damaged gene causing cancer, King has attempted to
understand where, along the way, something has gone wrong and what
can be done to fix it.
“I cannot separate doing science from doing good work,” she
says. “To do science is to try to improve the lives of people.”
Late afternoon in her office, while poring over tiny columns of
DNA test results, King spots the damaged gene that marks a
38-year-old woman for inherited breast cancer. She sucks in her
breath, stops nibbling her nails. Then the energy floods back in a
list of things to do: Reconfirm the test, call in a genetic
counselor, find out who’s the best oncologist in that woman’s city.
King is in the lab doing what she does best. Asking questions.
Making a plan.
Paula Bock is a writer for Pacific Northwest magazine. Harley Soltes
is the magazine’s photographer.