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Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
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Introduction
Tracking a Deadly Disease
Nancy Wexler is a hunter. The big game she's spent much of her life
pursuing is a particular gene, or unit of inheritance. People who
inherit this gene from one of their parents develop a fatal illness called
Huntington's disease. Nancy herself may have inherited this gene.
Nancy's long search for the Huntington's gene led her to villages in
Venezuela where a greater percentage of people suffer from the disease
than anywhere else in the world. There, year after year, Nancy and
her team worked with large families--grandparents, parents, and
children; uncles, aunts, and cousins. It's hard work, untangling family
relationships, testing for symptoms, and working with the villagers
whose blood and cooperation are critical tools for finding the cure.
Nancy grieves when villagers become ill with Huntington's, because
she knows how deeply they are suffering. She and they all share the
same DNA and possibly the same mistake in that DNA--they
literally are her family. But she never loses hope that science will
someday cure the disease.
Nancy's work on Huntington's has taken her around the world,
from London, England, to Papua, New Guinea. But ask her to name
a great adventure and she'll tell you it's not exotic travel but rather
science itself.
The search for the gene that causes Huntington's disease is a
real-life detective story. As Nancy puts it, "There's a killer on the
loose, and it's my job to find it before it claims more victims."
ix
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Huntington's isalways
on her mind.
It may even be
in hergenes.
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1
THE DANCING DISEASE
I n a small village on the shore of a lake in Venezuela, it seems as
if the whole population must be in the center of town today. Is it
a special occasion, a festival of some kind? People are milling
around near a low cinder-block building. Some are laughing and
Nancy and a
joking, some look more than a bit frightened, and everyone is Venezuelan child
sweating in the heat and humidity. who's bravely
contributed a blood
If you understand Spanish, you overhear comments like: "They
sample jointly shout
say it will help us" and "They need so much blood!" and "I did it. for joy (opposite).
You can do it." But listen closely and some of the shouted At Lake Maracaibo
in Venezuela,
comments don't make sense at all; the words form meaningless
children as young
phrases yelled over and over. as 6 years old
Near the doorway of the building, a woman with long, pale (above) sometimes
go fishing to help
blond hair picks up a small child and hugs her. A thin young man
their families earn
hesitates to enter the building and the woman says gently: a living.
"Remember, I told you, of course you can still go fishing after
Fidela takes your blood. No problem!" Then she hands some
candy to a young girl exiting the building. "Good for you, Ana!"
she says, nodding toward the small bandage on the girl's arm.
"I'm proud of you."
The blond woman is Nancy Wexler, an American scientist,
and right this minute she is hard at work on a research project
that may eventually save thousands of lives. Maybe even her own.
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Many of the adults in this village are behaving rather strangely.
Their arms and legs keep moving, even though they don't seem to
be doing anything or going anywhere. Some seem to be dancing,
HUNTER
though no one is watching their dance. These people are also
unusually thin.
GENE A few of the children move in unexpected ways, too. But rather
than seeming to dance or jerk their limbs, these children move
stiffly, arms and legs more like rigid boards.
Nancy emerges from the crowd, rounding the corner of the
building, followed by children, her arms around the ones pressing
close to her. At the side of the building, a
young doctor is examining a short, husky
man. The doctor isn't listening to the
man's heart or peering at his throat. He's a
neurologist and he's asking his patient to
follow an upturned finger with his eyes and
afterward to walk a straight line heel to toe.
The man is having difficulty with these
tasks. The doctor pats his shoulder and
Nancy hugs him, saying, "Thank you, Luis.
You're terrific!"
Luis walks away slowly, joining two
teenagers, a girl and a boy, who are waiting
for him. Nancy and the doctor confer. "Last
Fidela Gomez, a nurse year we weren't sure," the doctor says, "but now it's certain."
from Argentina, is so Nancy says, "And he has seven children."
skilled at drawing "How are they doing?"
blood and so amusing
that the woman "The little ones seem O.K., so far." Nancy gestures at the
waiting her turn young girl walking away with Luis. "But look how Maria walks."
appears relaxed and The doctor nods. "A little stiff," he says sadly. "And when it
at ease.
comes from the father . . . "
"Yes," Nancy says. "Then it may hit early."
The doctor beckons to a woman waiting under a palm tree and
Nancy moves away, still followed by children, many calling
"Nancy! Look at me!" Again, Nancy stations herself near the
doorway of the low building, watching people move in and out.
A little boy who's been clinging to Nancy suddenly runs off and
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joins a woman who is moving wildly, throwing her arms around.
The boy grabs a handful of her skirt and leads her slowly down a
path between palm trees. Nancy thinks, He's taking his mother home.
It is a normal thing here for children to take care of their parents,
rather than the other way around, when their parents are some of
the ones the villagers call "perdido." Perdido means "lost."
~Hunting Down Huntington's Disease
What's going on here? Why are some of the villagers called "lost"?
What's all this talk about blood?
Nancy Wexler is a kind of detective and she's working to hunt
down a killer, a mass murderer, in fact. But her work has nothing
to do with the police and the killer won't be captured at gunpoint.
The killer is a defective gene, a unit of inheritance. It causes a
disease called Huntington's disease. Huntington's, or HD, occurs
in some 10 people in every 100,000. It has killed thousands of
people all over the world. About 30,000 people in the United
States are affected by HD. Some 150,000 more have a genetic risk
of developing the disease. Singer-songwriter Woody Guthrie, the
man who wrote the song This Land Is Your Land, is probably the
most famous person to have had HD.
It's important to understand that HD is not a disease you can
"catch," like chicken pox or the flu. It is an inherited or genetic
disease and a type called an "autosomal dominant" disease.
Autosomal means that both males and females get it. Dominant
means only one parent has to have the disease for a child to have
a chance of inheriting it. It also means that if the child inherits the
disease, he or she will eventually get sick and die from it. (Some
other genetic diseases, like cystic fibrosis, are "recessive," meaning
the child needs to inherit abnormal genes from both parents in
order to show symptoms.)
Each child in a family whose mother or father has HD has
exactly the same one-in-two (or 50 percent) chance of inheriting
the gene that causes the disease, no matter how many siblings are
in the family. It's possible that none of the children of a parent
THE DANCING DISEASE 3
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with HD will inherit the gene; it's equally possible that all of them
will. The phrase often used to describe this fact is "chance has no
memory." (When you flip a quarter, the coin doesn't remember if it
HUNTER
came up heads or tails on previous flips.) If a child of a parent with
HD does not inherit the abnormal gene but rather the normal
GENE version of the gene, that person will never get sick with HD. His
or her own children will never get the disease, because only the
healthy gene is being passed down.
The symptoms of Huntington's usually begin to show up when
people are in their 30s or 40s, but the disease can begin in childhood
or even in old age. The first symptoms might be physical, such as
twitching, stumbling, or making jerking motions. The uncontrollable
movements are often described as "dancelike." When Nancy
lectures on HD, she often explains the abnormal movements this
way: "Seeing people with Huntington's is like watching a giant
puppet show. Their limbs are jerked around as if by an unseen
puppeteer, and there is nothing they can do about it." These
movements only stop when the person is asleep. Other symptoms
are mental and emotional; they may include memory problems,
depression, and acting aggressively. Eventually, people have
trouble swallowing, causing them to lose weight and waste away.
There is no cure or treatment for Huntington's disease.
When the parent who transmits the HD gene to a child is the
father, the disease sometimes shows
"Seeing people with Huntington's is up earlier than if the sick parent is
like watching a giant puppet show. the mother. There is a rare form of
Their limbs are jerked around as if by the disease in children, usually
an unseen puppeteer, and there is inherited from their fathers. That's
nothing they can do about it." why Nancy was concerned about
Maria, the young daughter of Luis,
who was walking stiffly. HD in children often causes rigidity or
stiffness, rather than movements.
As a scientist who studies Huntington's disease, Nancy is
interested in its cause or causes, its symptoms, its distribution in
the world, and how it might possibly be prevented, treated, and
cured. One way she gains information is to collect blood samples
from people in many different parts of the world. She takes blood
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Posing inside their
home, these family
members from the
village of Laguneta
appear healthy, but
some may be at risk
for Huntington's
disease.
samples from people who already have the disease, from their
relatives who are at genetic risk, and from other relatives as well.
She has worked in many places, including Naples, Italy; Barcelona,
Spain; Shanghai, China; and Israel.
During the course of these scientific investigations, Nancy and
the team she travels with have had many adventures. Often, each
place they visit presents its own challenge. One day they flew in a
tiny airplane to Papua, New Guinea, during a volcano alert. "It was
very dramatic," she told her friend and colleague Judy Lorimer when
she got back to her lab in New York. "All the trees had been cut
down so as not to block escape roads. And there were wonderful--
but scarily specific--signs posted everywhere telling what to do
when the volcano blew its top."
In Palma, Majorca, where there were a large number of families
with Huntington's, Nancy had expected to be able to use her
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basic Spanish. "The Majorcans spoke Catalan," she reported when
she got back. "My Spanish didn't get very far. But luckily, we
worked with a great scientific team from Palma."
HUNTER
And in tiny villages in the mountains of Peru, many miles
outside Lima, the team kept getting flat tires with no replacements
GENE available. They visited families with HD who all lived in a string
of villages along a main road but did not know of each other, even
though they may be related.
~The Worst and Best Place for
Technicians in Boston
Huntington's
analyze blood samples
from Venezuela for
hints on where to find
the HD gene. The Nancy has traveled to Venezuela more than to any other country.
blood must reach the
Every spring since 1979, she and a research team have flown there.
lab no later than three
days after it is drawn. These springtime trips are not about sightseeing and other holiday
activities; rather, they are about families
with Huntington's. Why choose
Venezuela and, in particular, the little
villages on Lake Maracaibo? Nancy and
her colleagues found out that this
region has more people with HD than
any other place on Earth.
What Nancy wants more than
anything in the world is to locate the
gene that causes Huntington's disease.
That gene holds the key to finding a
cure for HD--which is what Nancy is
after most of all! She hunts for this gene
in the DNA found in the blood samples.
She works with laboratories that
analyze the blood, searching for clues
that will tell scientists where the gene
may be hiding. When the gene is finally
identified, there will be a much greater chance for understanding
the gene's mistake and how to cure it. The blood samples donated
6
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Fort-de- Martinique
(FR.)
France
C a r i b b e a n S e a Castries
Saint Lucia
Saint Vincent and Barbados
The Grenadines
Kingstown
Aruba Netherlands Bridgetow
(Neth.) Antilles
Oranjestad (Neth.)
Puerto Saint
Curacao
Bolivar Aruba Bonaire George's
Grenada
Willemstad
Punto
Fijo
Riohacha Golfo
de Tobago Venezuela is a country
Venezuela Coro Isla la La Asuncion Port-of-
Tortuga Isla de Trinidad
Riecito Spain
Margarita and in northern South
Guiria
Maracaibo La Guaira Tobago
alledupar San Gulf
America (below)
Cabimas Cumana
Felipe Maracay Caracas of
Los Barcelona Paria Trinidad Atlantic
Baraquisimeto Valencia Teques
Lago bordered by the
Maturin
Ocean
de San Juan
Maracaibo San
Valera de los
Carlos Morros Caribbean Sea and the
Tucupita
Guanare Rio
Cojedes Atlantic Ocean. Lake
Barinas
Merida Ciudad Curiapo
Bolivar Ciudad Port Maracaibo is located
Guayana
e Rio Orinoco Kaitum
in the northwest part
Cucuta Apur Cabruta
San Bochinche
San Rio Guasipati
Fernando Caicara
Matthews
Cristobal Ciudad
Tumeremo Ridge
El Amparo PiarEmbaise of the country (left).
de El
Bucaramanga Guri
Arauca El Jobal Dorado
La Paragua Rio Cuyuni
Puerto
Canaima Peters Mine
Carreno
Rio Guyana
V e n e z u e l a Car
Paz de Issano
Tunja Rio Rio oni
Meta San Juan
Rio Puerto
de Manapiare
Ayacucho Caura
Santa Elena
Orind North America
de Uairen
San Fernando
de Atabapo
Normandia
Vila Brasil
C o l o m b i a Puerto
re
Guavia Inirida Bonfim
Esmeralda Rio Uraricoera
Rio
Boa Vista South America
e
Rio P a c i f i c
San Jose del RioGuainia Orinoco
Guaviare Casiquiar O c e a n Atlantic
Rio
Calamar Ocean
Branco Novo
Cucui Rio Paraiso
Sao Gabriel
da Cachoeira Rio
Negro Represa
Balbina
B r a z i l
today by the people in the village will travel by plane tomorrow
to a lab at Harvard University in Boston, where a scientist named
Jim Gusella and his collaborators will analyze them, looking for
clues that may lead them to the HD gene. The blood must reach
the lab within 72 hours. Today was a "draw day," a good day for
drawing blood because some members of the team are leaving
tomorrow and can take the blood samples with them. It is
impossible to ship them alone--and besides, they are much too
valuable.
Late in the afternoon, Nancy relaxes in a simple outdoor café
near the community center building. With her are Harvard
University professors Anne Young and her husband Jack Penney
who have spent the day examining, filming, and drawing blood
samples from over 200 villagers. They drink Cokes. They've
worked hard today as they have on every day of this year's trip.
Are they any closer now to finding the gene than when the trip
began, when all the trips here began? Nancy is certain they're
THE DANCING DISEASE 7
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getting closer. "I have to believe it," she says to Anne and Jack, "and
I'm convinced it's true."
A child wanders over and sits on her lap. Another child chases a
HUNTER
small pig down a path. "I have to believe it for the children," Nancy
adds. "I look at them and want to believe they'll all keep developing
GENE and learning and have a future. But every year we come here and
see that some of them are going downhill instead. Someday we'll
celebrate finding the cure with all the families here."
Anne lifts her glass. She says: "To the gene! To the cure!" They
drink to the gene and the cure coming quickly because they know
they are in a race against time.
~Working on Home Ground
It's a Wednesday morning and Nancy, instead of being off in
Venezuela or another foreign country, is actually to be found in
her office at Columbia University in New York City. Not that
she's at her desk very much. She's mostly flying up and down the
halls, her pale blond hair floating behind her, as she drops in to
visit people in other offices--particularly her collaborators, Judy
Lorimer and Julie Porter, plus scientists who work nearby. Judy is
project director and Julie is data chief for the Venezuela project.
Right now Judy and Julie are busy helping Nancy catch up with
what she missed during a trip to
"We suddenly came upon two England. Judy hands Nancy all the
women, mother and daughter, both papers that have piled up while she
tall, thin, almost cadaverous, both was away. There are reports of
bowing, twisting, grimacing." important experiments, journals with
articles on many hereditary diseases,
invitations for Nancy to speak at conferences. Laughing, Nancy
says to Judy, "There used to be a television program with the tag
line `Have gun, will travel.' Well, what I say is, `Have science
degree, will travel.'" Clutching an armful of work, Nancy gives
each of her colleagues a hug and hurries back to her office.
Everyone Nancy encounters is at risk of receiving one of her
hugs. She's known among her colleagues and friends for these big
8
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hugs and for her brilliant smile, but most of all for her scientific
work. Today Nancy's just back from London, where she visited
the laboratory of scientist Dr. Gillian Bates, who has been
studying some special mice that she developed. Gill genetically
modified these mice to have symptoms resembling Huntington's
disease, so they can be used to test new treatments as they are
developed. When Nancy travels anywhere, just as when she's in
Venezuela or "home" in her own office, she is constantly reading
and writing about HD, discussing it with colleagues on the phone,
in laboratories, or offices, lecturing about it, or visiting nursing
homes where patients with the illness are cared for. Huntington's
is always on her mind.
It may even be in her genes.
~An Illness Like No Other
Huntington's disease led Nancy into the field of
neuropsychology. You can figure out what a
neuropsychologist does by taking apart the word.
The prefix neuro comes from the Greek word
neuron, which means "nerve." You probably know
that psychologists study human behavior and the
workings of the human mind. Neuropsychologists
go one step further. They study the relationship
between the central nervous system (the brain and
spine) and behavior. They specialize in disorders of the
brain that cause problems with thinking, emotions, and behavior.
Huntington's disease is a disorder that fits this description George Huntington
perfectly. (18501916), son and
grandson of doctors,
People always ask Nancy how Huntington's disease got its name.
was the first to tell the
She tells them about George Huntington, the son and grandson of world about the illness
doctors, who lived in New York State during the 19th century. An named for him and
that it is inherited from
observant child, he paid close attention to the inhabitants of his
parent to child.
village. He particularly noticed some people who were behaving
strangely. Later, after becoming a doctor himself, he wrote about his
recollections: "We suddenly came upon two women, mother and
THE DANCING DISEASE 9
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daughter, both tall, thin, almost cadaverous, both bowing, twisting,
grimacing. I stared in wonderment, almost in fear. What could it
mean?"
HUNTER
George Huntington keenly observed the patients of his grandfather
and father before him. Three generations of doctors in his family led
GENE George to be the first person in the world to describe accurately
the hereditary pattern of Huntington's disease.
In 1872, when only 22, he published a paper on the disease,
which has been known as Huntington's ever since. At first the
illness was called "Huntington's chorea." Chorea is from the Greek
word for dance, like the word "choreographer," someone who
creates dances. You can understand why chorea was an appropriate
word to describe this illness.
The evidence from Venezuela fills the filing cabinets in Nancy's
office. The papers in these cabinets contain data on genes, blood,
disease symptoms, and family relationships of thousands of
Venezuelan villagers. Sometimes it seems as if, when a drawer is
opened, the sound of many voices speaking Spanish fills the office.
There's other evidence of Nancy's Venezuelan trips as well. A
photograph of a smiling little boy with brown skin and big blue-
green eyes is propped on her desk. He is important, not only to
Nancy but to thousands of people throughout the world. Later,
we'll see why this is true.
~A Scientist's Work
Today Nancy is wearing black pants, a bright orange knit top, and
black flats. It's getting close to Halloween, which might explain
the color scheme. The long amber beads of her necklace swing
when she moves and so do her sparkly dangling earrings. Her
blue eyes are as lively as her movements. When her collaborators
have left, Nancy picks up the phone and taps in the number of
her father across the country in Los Angeles, California. She tells
him about the mice in the London lab, and they laugh together
about the time she was raising white mice for an experiment when
she was a kid. "How's your work going?" Nancy asks her father.
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The Wexler sisters,
Nancy (left) and Alice,
have been jointly
involved in the fight
against HD for several
decades. In 1995 Alice
wrote Mapping Fate,
a memoir about the
Wexler family and HD.
His work? Milton Wexler is 97! Nevertheless, he still works
part time, seeing psychotherapy patients.
In addition to psychotherapy, Nancy's father is also
involved with Huntington's and they have many joint
projects to discuss. He demonstrates another good
thing about science: People retire if they want to, but
they often don't want to. Many scientists become so
interested in what they're doing they keep working as long
as they can. In fact, scientists of any age have been known to say
that their efforts often seem more like play than work.
Next, Nancy calls her sister, Alice, three years her senior. Alice
also lives in California. She has a Ph.D. in history and has
published a two-volume biography of Emma Goldman, a famous
anarchist. Alice has also published a riveting memoir of the Wexler
family and the origins of the Hereditary Disease Foundation. The
book, Mapping Fate: A Memoir of Family, Risk, and Genetic Research,
also describes the quest for the HD gene. She is now working on
a new book, on the social history of HD. Today, Alice and Nancy
discuss the researchers Nancy met with in London and the most
recent advances in drugs that might treat the disease.
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Nancy often spends time in Los Angeles. She's the president of
the Hereditary Disease Foundation, a nonprofit foundation started
by her father to find a cure for the disease after Alice and Nancy's
HUNTER
mother was diagnosed with HD. The group raises funds for research
on HD and related inherited diseases. The foundation also sponsors
GENE unique interdisciplinary workshops for scientists who work on HD
Although world- and other genetic diseases. While she's in Los Angeles, Nancy stays
famous architect at her father's apartment. She's a successful professional woman but
Frank Gehry helped still enjoys being a daughter living with a parent--at least some of
design Nancy's
apartment, her home the time.
is not as eye-popping But right now, here in her New York office, Nancy's life is
as Gehry's Walt almost too hectic. She's scheduled to give a guest lecture on
Disney Concert Hall
in Los Angeles! genetics at the medical school at Columbia University. Later in
the week, she'll lecture at the nursing school. At her
desk, going over her notes for lectures, reading
reports of new research, she raises her head now
and then to stare out the window. The view
from her corner office is so magnificent it's
amazing that anyone can get any work done
here. The Hudson River flows beneath the
enormous windows, wide and blue and peaceful.
It's a wonderful scene to view when she needs a
spot of calm in the middle of the
chaos of work. Still, often while
she seems to be staring at the
beautiful river, she is seeing the
villagers in Venezuela.
When it's time for Nancy,
Judy, and Julie to leave, Nancy
packs her briefcase with papers
she may read at home tonight.
She often works in an office in
her apartment. She loves her
apartment and is proud of the fact
that its loftlike interior was partly
designed by Frank Gehry, the
famous architect who designed
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the Walt Disney Concert Hall in Los
Angeles and the Guggenheim Museum
in Bilbao, Spain. She also mentions
that Gehry is vice president and wife
Berta Gehry is treasurer of the
Hereditary Disease Foundation. Both
are founders of the foundation and
close friends of Nancy's.
But maybe she won't work tonight.
She's been traveling so much and she's
eager to spend some time with her
long-time partner, Dr. Herbert Pardes.
Herb is president and CEO of New
YorkPresbyterian Hospital, so he and
Nancy have many medical interests in
common. They also love to go to
plays, movies, concerts, and the ballet
when they can find the time. Maybe tonight they'll order Chinese Drs. Herb Pardes and
food since neither of them cooks. After dinner Nancy will leave Nancy Wexler believe
that even the most
her papers unread and they'll go to the movies--one or two or dedicated scientists
three to make up for lost time. Nancy dashes down the hall to ask deserve an occasional
Judy and Julie to recommend some good movies. She's been vacation. Italy is one
of their favorite places
traveling for too long a time to know what's happening in New to relax.
York. She smiles to herself and thinks, It feels really great to be home.
THE DANCING DISEASE 13
Representative terms from entire chapter:
blood samples
