Lynn Margulis, a biologist whose work on the origin of cells
helped transform the study of evolution, died on Tuesday at her home in Amherst,
Mass. She was 73.
She died five days after suffering a hemorrhagic stroke, said Dorion Sagan, a
son she had with her first husband, the cosmologist Carl Sagan.
Dr. Margulis, who had the title of distinguished university professor of
geosciences at the University of Massachusetts, Amherst, since 1988, drew upon
earlier, ridiculed ideas when she first promulgated her theory, in the late
1960s, that cells with nuclei, which are known as eukaryotes and include all the
cells in the human body, evolved as a result of symbiotic relationships among
The hypothesis was a direct challenge to the prevailing neo-Darwinist belief
that the primary evolutionary mechanism was random mutation.
Rather, Dr. Margulis argued that a more important mechanism was symbiosis; that
is, evolution is a function of organisms that are mutually beneficial growing
together to become one and reproducing. The theory undermined significant
precepts of the study of evolution, underscoring the idea that evolution began
at the level of micro-organisms long before it would be visible at the level of
“She talked a lot about the importance of micro-organisms,” said her daughter,
Jennifer Margulis. “She called herself a spokesperson for the microcosm.”
The manuscript in which Dr. Margulis first presented her findings was rejected
by 15 journals before being published in 1967 by the Journal of Theoretical
Biology. An expanded version, with additional evidence to support the theory —
which was known as the serial endosymbiotic theory — became her first book,
“Origin of Eukaryotic Cells.”
A revised version, “Symbiosis in Cell Evolution,” followed in 1981, and though
it challenged the presumptions of many prominent scientists, it has since become
accepted evolutionary doctrine.
“Evolutionists have been preoccupied with the history of animal life in the last
500 million years,” Dr. Margulis wrote in 1995. “But we now know that life
itself evolved much earlier than that. The fossil record begins nearly 4,000
million years ago! Until the 1960s, scientists ignored fossil evidence for the
evolution of life, because it was uninterpretable.
“I work in evolutionary biology, but with cells and micro-organisms. Richard
Dawkins, John Maynard Smith, George Williams, Richard Lewontin, Niles Eldredge
and Stephen Jay Gould all come out of the zoological tradition, which suggests
to me that, in the words of our colleague Simon Robson, they deal with a data
set some three billion years out of date.”
Lynn Petra Alexander was born on March 5, 1938, in Chicago, where she grew up in
a tough neighborhood on the South Side. Her father was a lawyer and a
businessman. Precocious, she graduated at 18 from the University of Chicago,
where she met Dr. Sagan as they passed each other on a stairway.
She earned a master’s degree in genetics and zoology from the University of
Wisconsin and a Ph.D. in genetics from the University of California, Berkeley.
Before joining the faculty at Massachusetts, she taught for 22 years at Boston
Dr. Margulis was also known, somewhat controversially, as a collaborator with
and supporter of James E. Lovelock, whose Gaia theory states that Earth itself —
its atmosphere, the geology and the organisms that inhabit it — is a
self-regulating system, maintaining the conditions that allow its perpetuation.
In other words, it is something of a living organism in and of itself.
Dr. Margulis’s marriage to Dr. Sagan ended in divorce, as did a marriage to
Thomas N. Margulis, a chemist. Dr. Sagan died in 1996.
In addition to her daughter and her son Dorion, a science writer with whom she
sometimes collaborated, she is survived by two other sons, Jeremy Sagan and
Zachary Margulis-Ohnuma; three sisters, Joan Glashow, Sharon Kleitman and Diane
Alexander; two half-brothers, Robert and Mark Alexander; a half-sister, Sara
Alexander; and nine grandchildren.
“More than 99.99 percent of the species that have ever existed have become
extinct,” Dr. Margulis and Dorion Sagan wrote in “Microcosmos,” a 1986 book that
traced, in readable language, the history of evolution over four billion years,
“but the planetary patina, with its army of cells, has continued for more than
three billion years. And the basis of the patina, past, present and future, is
the microcosm — trillions of communicating, evolving microbes.”
The genome pioneer J. Craig Venter has taken another step in his quest to
create synthetic life, by synthesizing an entire bacterial genome and using it
to take over a cell.
Dr. Venter calls the result a “synthetic cell” and is presenting the research as
a landmark achievement that will open the way to creating useful microbes from
scratch to make products like vaccines and biofuels. At a press conference
Thursday, Dr. Venter described the converted cell as “the first self-replicating
species we’ve had on the planet whose parent is a computer.”
“This is a philosophical advance as much as a technical advance,” he said,
suggesting that the “synthetic cell” raised new questions about the nature of
Other scientists agree that he has achieved a technical feat in synthesizing the
largest piece of DNA so far — a million units in length — and in making it
accurate enough to substitute for the cell’s own DNA.
But some regard this approach as unpromising because it will take years to
design new organisms, and meanwhile progress toward making biofuels is already
being achieved with conventional genetic engineering approaches in which
existing organisms are modified a few genes at a time.
Dr. Venter’s aim is to achieve total control over a bacterium’s genome, first by
synthesizing its DNA in a laboratory and then by designing a new genome stripped
of many natural functions and equipped with new genes that govern production of
“It’s very powerful to be able to reconstruct and own every letter in a genome
because that means you can put in different genes,” said Gerald Joyce, a
biologist at the Scripps Research Institute in La Jolla, Calif.
In response to the scientific report, President Obama asked the White House
bioethics commission on Thursday to complete a study of the issues raised by
synthetic biology within six months and report back to him on its findings. He
said the new development raised “genuine concerns,” though he did not specify
Dr. Venter took a first step toward this goal three years ago, showing that the
natural DNA from one bacterium could be inserted into another and that it would
take over the host cell’s operation. Last year, his team synthesized a piece of
DNA with 1,080,000 bases, the chemical units of which DNA is composed.
In a final step, a team led by Daniel G. Gibson, Hamilton O. Smith and Dr.
Venter report in Thursday’s issue of the journal Science that the synthetic DNA
takes over a bacterial cell just as the natural DNA did, making the cell
generate the proteins specified by the new DNA’s genetic information in
preference to those of its own genome.
The team ordered pieces of DNA 1,000 units in length from Blue Heron, a company
that specializes in synthesizing DNA, and developed a technique for assembling
the shorter lengths into a complete genome. The cost of the project was $40
million, most of it paid for by Synthetic Genomics, a company Dr. Venter
But the bacterium used by the Venter group is unsuitable for biofuel production,
and Dr. Venter said he would move to different organisms. Synthetic Genomics has
a contract from Exxon to generate biofuels from algae. Exxon is prepared to
spend up to $600 million if all its milestones are met. Dr. Venter said he would
try to build “an entire algae genome so we can vary the 50 to 60 different
parameters for algae growth to make superproductive organisms.”
On his yacht trips round the world, Dr. Venter has analyzed the DNA of the many
microbes in seawater and now has a library of about 40 million genes, mostly
from algae. These genes will be a resource to make captive algae produce useful
chemicals, he said.
Some other scientists said that aside from assembling a large piece of DNA, Dr.
Venter has not broken new ground. “To my mind Craig has somewhat overplayed the
importance of this,” said David Baltimore, a geneticist at Caltech. He described
the result as “a technical tour de force,” a matter of scale rather than a
“He has not created life, only mimicked it,” Dr. Baltimore said.
Dr. Venter’s approach “is not necessarily on the path” to produce useful
microorganisms, said George Church, a genome researcher at Harvard Medical
School. Leroy Hood, of the Institute for Systems Biology in Seattle, described
Dr. Venter’s report as “glitzy” but said lower-level genes and networks had to
be understood first before it would be worth trying to design whole organisms
In 2002 Eckard Wimmer, of the State University of New York at Stony Brook,
synthesized the genome of the polio virus. The genome constructed a live polio
virus that infected and killed mice. Dr. Venter’s work on the bacterium is
similar in principle, except that the polio virus genome is only 7,500 units in
length, and the bacteria’s genome is more than 100 times longer.
Friends of the Earth, an environmental group, denounced the synthetic genome as
“dangerous new technology,” saying that “Mr. Venter should stop all further
research until sufficient regulations are in place.”
The genome Dr. Venter synthesized is copied from a natural bacterium that
infects goats. He said that before copying the DNA, he excised 14 genes likely
to be pathogenic, so the new bacterium, even if it escaped, would be unlikely to
cause goats harm.
Dr. Venter’s assertion that he has created a “synthetic cell” has alarmed people
who think that means he has created a new life form or an artificial cell. “Of
course that’s not right — its ancestor is a biological life form,” said Dr.
Joyce of Scripps.
Dr. Venter copied the DNA from one species of bacteria and inserted it into
another. The second bacteria made all the proteins and organelles in the
so-called “synthetic cell,” by following the specifications implicit in the
structure of the inserted DNA.
“My worry is that some people are going to draw the conclusion that they have
created a new life form,” said Jim Collins, a bioengineer at Boston University.
“What they have created is an organism with a synthesized natural genome. But it
doesn’t represent the creation of life from scratch or the creation of a new
life form,” he said.
One of the most celebrated findings in modern psychiatry — that a single gene
helps determine one’s risk of depression in response to a divorce, a lost job or
another serious reversal — has not held up to scientific scrutiny, researchers
The original finding, published in 2003, created a sensation among scientists
and the public because it offered the first specific, plausible explanation of
why some people bounce back after a stressful life event while others plunge
into lasting despair.
The new report, by several of the most prominent researchers in the field, does
not imply that interactions between genes and life experience are trivial; they
are almost certainly fundamental, experts agree.
But it does suggest that nailing down those factors in a precise way is far more
difficult than scientists believed even a few years ago, and that the original
finding could have been due to chance. The new report is likely to inflame a
debate over the direction of the field itself, which has found that the genetics
of illnesses like schizophrenia and bipolar disorder remain elusive.
“This gene/life experience paradigm has been very influential in psychiatry,
both in the studies people have done and the way data has been interpreted,”
said Dr. Kenneth S. Kendler, a professor of psychiatry and human genetics at
Virginia Commonwealth University, “and I think this paper really takes the wind
out of its sails.”
Others said the new analysis was unjustifiably dismissive. “What is needed is
not less research into gene-environment interaction,” Avshalom Caspi, a
neuroscientist at Duke University and lead author of the original paper, wrote
in an e-mail message, “but more research of better quality.”
The original study was so compelling because it explained how nature and nurture
could collude to produce a complex mood problem. It followed 847 people from
birth to age 26 and found that those most likely to sink into depression after a
stressful event — job loss, sexual abuse, bankruptcy — had a particular variant
of a gene involved in the regulation of serotonin, a brain messenger that
affects mood. Those in the study with another variant of the gene were
significantly more resilient.
“I think what happened is that people who’d been working in this field for so
long were desperate to have any solid finding,” Kathleen R. Merikangas, chief of
the genetic epidemiology research branch of the National Institute of Mental
Health and senior author of the new analysis, said in a phone interview. “It was
exciting, and some people thought it was the finding in psychiatry, a major
The excitement spread quickly. Newspapers and magazines reported the finding.
Columnists, commentators and op-ed writers emphasized its importance. The study
provided some despairing patients with comfort, and an excuse — “Well, it is in
my genes.” It reassured some doctors that they were medicating an organic
disorder, and stirred interest in genetic testing for depression risk.
Since then, researchers have tried to replicate the gene finding in more than a
dozen studies. Some found similar results; others did not. In the new study,
being published Wednesday in The Journal of the American Medical Association,
Neil Risch of the University of California, San Francisco, and Dr. Merikangas
led a coalition of researchers who identified 14 studies that gathered the same
kinds of data as the original study. The authors reanalyzed the data and found
“no evidence of an association between the serotonin gene and the risk of
depression,” no matter what people’s life experience was, Dr. Merikangas said.
By contrast, she said, a major stressful event, like divorce, in itself raised
the risk of depression by 40 percent.
The authors conclude that the widespread acceptance of the original findings was
premature, writing that “it is critical that health practitioners and scientists
in other disciplines recognize the importance of replication of such findings
before they can serve as valid indicators of disease risk” or otherwise change
Dr. Caspi and other psychiatric researchers said it would be equally premature
to abandon research into gene-environment interaction, when brain imaging and
other kinds of evidence have linked the serotonin gene to stress sensitivity.
“This is an excellent review paper, no one is questioning that,” said Myrna
Weissman, a professor of epidemiology and psychiatry at Columbia. “But it
ignored extensive evidence from humans and animals linking excessive sensitivity
to stress” to the serotonin gene.
Dr. Merikangas said she and her co-authors deliberately confined themselves to
studies that could be directly compared to the original. “We were looking for
replication,” she said.
DALLAS (AP) — A Dallas man
who spent more than 27 years in prison for a murder he didn't commit was freed
Tuesday, after being incarcerated longer than any other wrongfully convicted
U.S. inmate cleared by DNA testing.
James Lee Woodard stepped
out of the courtroom and raised his arms to a throng of photographers.
Supporters and other people gathered outside the court erupted in applause.
"No words can express what a tragic story yours is," state District Judge Mark
Stoltz told Woodard at a brief hearing before his release.
Woodard, cleared of the 1980 murder of his girlfriend, became the 18th person in
Dallas County to have his conviction cast aside. That's a figure unmatched by
any county nationally, according to the Innocence Project, a New York-based
legal center that specializes in overturning wrongful convictions.
"I thank God for the existence of the Innocence Project," Woodard, 55, told the
court. "Without that, I wouldn't be here today. I would be wasting away in
Overall, 31 people have been formally exonerated through DNA testing in Texas,
also a national high. That does not include Woodard and at least three others
whose exonerations will not become official until Gov. Rick Perry grants pardons
or the Texas Court of Criminal Appeals formally accepts the ruling of lower
courts that have already recommended exoneration.
Woodard was sentenced to life in prison in July 1981 for the murder of a
21-year-old Dallas woman found raped and strangled near the banks of the Trinity
He was convicted primarily on the basis of testimony from two eyewitnesses, said
Natalie Roetzel, the executive director of the Innocence Project of Texas. One
has since recanted in an affidavit. As for the other, "we don't believe her
testimony was accurate," Roetzel said.
Like nearly all the exonorees, Woodard has maintained his innocence throughout
his time in prison. But after filing six writs with an appeals court, plus two
requests for DNA testing, his pleas of innocence became so repetitive and
routine that "the courthouse doors were eventually closed to him and he was
labeled a writ abuser," Roetzel said.
"On the first day he was arrested, he told the world he was innocent ... and
nobody listened," Jeff Blackburn, chief counsel for the Innocence Project of
Texas, said during Tuesday's hearing.
He even stopped attending his parole hearings because gaining his release would
have meant confessing to a crime he didn't do.
"It says a lot about your character that you were more interested in the truth
than your freedom," the judge told Woodard after making his ruling.
Blackburn and prosecutors hailed Tuesday's hearing as a landmark moment of
frequent adversaries working together.
Since the DNA evidence was tied to rape and Woodard was convicted of murder,
Innocence Project attorneys had to prove that the same person committed both
crimes. They said they couldn't have done that without access to evidence
provided by Dallas County District Attorney Craig Watkins' office.
"You've got to have very good lawyers with a lot of experience and skill ...
working on both ends of this case, hard," Blackburn said. "And you've also got
to have government power behind what you do."
Under Watkins, Dallas County has a program supervised by the Innocence Project
of Texas that is reviewing hundreds of cases of convicts who have requested DNA
testing to prove their innocence.
While the number of exonerations on Watkins' watch continues to grow, he said
this one was a little different.
"I saw the human side of it, and seeing the human said of it just gives you more
courage to advocate for issues like this," said Watkins, who had breakfast with
Woodard on Tuesday morning. "It gives me that resolve to go even further to find
out who (the killer) is so that we can get him into custody."
Woodard said his family was "small and scattered," although he pointed out a
niece in the courtroom. He said his biggest regret was not being with his mother
when she died.
"I can tell you what I'd like to do first: breathe fresh, free air," Woodard
said during a news conference in the courtroom after the hearing. "I don't know
what to expect. I haven't been in Dallas since buses were blue."
We are fast approaching Father’s Day, the festive occasion on
which we plague Dad with yet another necktie or collect phone call and just
generally strive to remind the big guy of the central verity of paternity — that
it’s a lot more fun to become a father than to be one. “I won’t lie to you,”
said the great Homer Simpson. “Fatherhood isn’t easy like motherhood.” Yet in
our insistence that men are more than elaborately engineered gamete vectors, we
neglect the marvels of their elaborately engineered gametes. As the scientists
who study male germ cells will readily attest, sperm are some of the most
extraordinary cells of the body, a triumph of efficient packaging, sleek design
and superspecialization. Human sperm are extremely compact, and they’ve been
stripped of a normal cell’s protein-making machinery; but when cast into the
forbidding environment of the female reproductive tract, they will learn on the
job and change their search strategies and swim strokes as needed.
Sperm are also fast and as cute as tadpoles. They have chubby teardrop heads and
stylish, tapering tails, and they glide, slither, bumble and do figure-eights.
So while a father may not be entitled to take the same pride in his sperm as he
does in his kids, it’s fair to celebrate the single-minded cellular commas that
helped give those children their start.
Sperm are pretty much the tiniest cells in the human body. The head of a mature,
semen-ready sperm cell spans about 5 microns, or two-thousandths of an inch,
less than half the width of a white blood cell or a skin cell. And a sperm cell
is absurdly dwarfed by its female counterpart, the egg, which, fittingly or not,
is among the biggest cells in the body. At 30 times the width of a sperm, the
egg is massive enough to be seen with the naked eye.
But men have the overwhelming quantitative edge in the gamete games. Whereas
current evidence suggests that a human female is born with all the eggs she will
have, and that only about 500 of her natal stock of one million will ever ripen
and have a shot at fertilization, a male from puberty onward is pretty much a
nonstop sperm bakery. Each testicle generates more than 4 million new sperm per
hour, for a lifetime total of maybe 12 trillion sperm per man (although the
numbers vary with the day and generally slope downward with age).
The average ejaculation consists mostly of a teaspoon’s worth of nonspermic
seminal fluid, a viscous mix of sugars, citric acid and other ingredients
designed to pamper and power the sperm cells and prepare them for difficult
times ahead; the sperm proper account for only about 1 percent of the semen
mass. Yet in that 1 percent may be found 150 million sperm, 150 million human
aspirants yearning to meet their mammoth other halves.
To which one can crack, dream on. Not only are there far too few eggs to go
around, but also the majority of sperm couldn’t fertilize an ovum if it were
plunked down in front of them. “Only a perfectly normal sperm can penetrate an
egg,” said Dr. Harry Fisch, a urologist at Columbia University Medical Center,
“and the majority of sperm are abnormally shaped.” Some may have pinheads,
others have two heads, some lack tails, a third don’t move at all. As a rule,
Dr. Fisch said, a man is lucky if 15 percent of his sperm are serviceable. “One
guy I saw had 22 percent,” he said, “but that’s rare.”
Creating sperm is a complex, multistep operation in which immature cells spend
one or two months wending through a labyrinth of tubules coiled in the testes,
at each stage losing a bit more of the blobby contours and yolky contents of
standard cells and assuming the streamlined profile of sperm cells. The
operation is a delicate one that must be performed at temperatures some 2
degrees below that of the body, which is why the testicles hang outside the
body, where breezes can keep them cool; why a man hoping to become a father is
advised to skip the hot baths and saunas; and why a bout of high fever can
disrupt fertility for months.
The model sperm that emerges at tubule’s end has, like an insect, three basic
body segments. Of crowning importance is the head, which is taken up largely by
a supercondensed tangle of 23 chromosomes, half the complement of DNA found in a
normal body cell and thus the right number to merge with an egg’s 23 chromosomes
and begin tapping out a whole new body. At the tip of the sperm head is the
acrosome, a specialized sack of enzymes that help the sperm penetrate through
what Joseph S. Tash, a male fertility expert at the University of Kansas Medical
Center, calls the “forest” of ancillary cells and connective tissue that
surrounds the ripe, ready egg.
Below the head is the midpiece, which is packed with the tiny engines called
mitochondria that lend the sperm its motility, and below the midpiece is the
tail, a bundle of 11 entwined filaments that thrashes and propels a sperm
forward at the estimable pace of one-twelfth of an inch per minute, the
equivalent of a human striding at four miles an hour.
Sperm do not really hit their stride until they are deposited in the female
reproductive tract, at which point chemical signals from the vaginal and
cervical mucus seem to spark them to life. Released from the buffering folds of
their seminal delivery blanket, they at first swim straight ahead,
torpedo-style, “with very little back and forth of the head,” Dr. Tash said.
They may linger in the cervical mucus for a couple of days, or cross the cervix
and enter the uterus.
If an egg has burst from its ovarian follicle and been plucked by a fallopian
tube, sperm can sense its signature, a telltale shift in calcium ions. The sperm
become “hyperactivated,” said Moira O’Bryan, a sperm expert at Monash University
in Australia, switching to “a crazed figure-eight motion” ideal for boring
through barriers. The ovum eggs them on, signaling some to play the sacrificial
kamikaze and explode their enzyme sacks prematurely, loosening the corridor for
other, shapelier sperm to pass through intact. A few dozen fine-figured sperm
find their way to the final barrier, the egg’s plasma membrane, where they
waggle with all their crazy-eight might and beg to be chosen — but only one will
be taken, will fuse with the egg and be absorbed into its rich inner sanctum.
In a fraction of a second, an electrical, ionic jolt dramatically changes the
egg’s outer coat, to forestall the lethal intrusion of additional sperm.
The wheels are in motion. How do you like your new tie?
The test, the counselor said, had come back positive.
Katharine Moser inhaled sharply. She thought she was as ready as anyone could be
to face her genetic destiny. She had attended a genetic counseling session and
visited a psychiatrist, as required by the clinic. She had undergone the
recommended neurological exam. And yet, she realized in that moment, she had
never expected to hear those words.
“What do I do now?” Ms. Moser asked.
“What do you want to do?” the counselor replied.
“Cry,” she said quietly.
Her best friend, Colleen Elio, seated next to her, had already begun.
Ms. Moser was 23. It had taken her months to convince the clinic at
NewYork-Presbyterian Hospital/Columbia University Medical Center in Manhattan
that she wanted, at such a young age, to find out whether she carried the gene
for Huntington’s disease.
Huntington’s, the incurable brain disorder that possessed her grandfather’s body
and ravaged his mind for three decades, typically strikes in middle age. But
most young adults who know the disease runs in their family have avoided the DNA
test that can tell whether they will get it, preferring the torture — and hope —
of not knowing.
Ms. Moser is part of a vanguard of people at risk for Huntington’s who are
choosing to learn early what their future holds. Facing their genetic heritage,
they say, will help them decide how to live their lives.
Yet even as a raft of new DNA tests are revealing predispositions to all kinds
of conditions, including breast cancer, depression and dementia, little is known
about what it is like to live with such knowledge.
“What runs in your own family, and would you want to know?” said Nancy Wexler, a
neuropsychologist at Columbia and the president of the Hereditary Disease
Foundation, which has pioneered Huntington’s research. “Soon everyone is going
to have an option like this. You make the decision to test, you have to live
with the consequences.”
On that drizzly spring morning two years ago, Ms. Moser was feeling her way,
with perhaps the most definitive and disturbing verdict genetic testing has to
offer. Anyone who carries the gene will inevitably develop Huntington’s.
She fought her tears. She tried for humor.
Don’t let yourself get too thin, said the clinic’s social worker. Not a problem,
Ms. Moser responded, gesturing to her curvy frame. No more than two drinks at a
time. Perhaps, Ms. Moser suggested to Ms. Elio, she meant one in each hand.
Then came anger.
“Why me?” she remembers thinking, in a refrain she found hard to shake in the
coming months. “I’m the good one. It’s not like I’m sick because I have
emphysema from smoking or I did something dangerous.”
The gene that will kill Ms. Moser sits on the short arm of everyone’s fourth
chromosome, where the letters of the genetic alphabet normally repeat C-A-G as
many as 35 times in a row. In people who develop Huntington’s, however, there
are more than 35 repeats.
No one quite knows why this DNA hiccup causes cell death in the brain, leading
Huntington’s patients to jerk and twitch uncontrollably and rendering them
progressively unable to walk, talk, think and swallow. But the greater the
number of repeats, the earlier symptoms tend to appear and the faster they
Ms. Moser’s “CAG number” was 45, the counselor said. She had more repeats than
her grandfather, whose first symptoms — loss of short-term memory, mood swings
and a constant ticking noise he made with his mouth — surfaced when he turned
50. But it was another year before Ms. Moser would realize that she could have
less than 12 years until she showed symptoms.
Immediately after getting her results, Ms. Moser was too busy making plans.
“I’m going to become super-strong and super-balanced,” she vowed over lunch with
Ms. Elio, her straight brown hair pulled into a determined bun. “So when I start
to lose it I’ll be a little closer to normal.”
In the tumultuous months that followed, Ms. Moser often found herself unable to
remember what normal had once been. She forced herself to renounce the crush she
had long nursed on a certain firefighter, sure that marriage was no longer an
option for her. She threw herself into fund-raising in the hopes that someone
would find a cure. Sometimes, she raged.
She never, she said, regretted being tested. But at night, crying herself to
sleep in the dark of her lavender bedroom, she would go over and over it. She
was the same, but she was also different. And there was nothing she could do.
A Lesson in Stigma
Ms. Moser grew up in Connecticut, part of a large Irish Catholic family. Like
many families affected by Huntington’s, Ms. Moser’s regarded the disease as a
curse, not to be mentioned even as it dominated their lives in the form of her
grandfather’s writhing body and unpredictable rages.
Once, staying in Ms. Moser’s room on a visit, he broke her trundle bed with his
violent, involuntary jerking. Another time, he came into the kitchen naked, his
underpants on his head. When the children giggled, Ms. Moser’s mother defended
her father: “If you don’t like it, get out of my house and go.”
But no one explained what had happened to their grandfather, Thomas Dowd, a
former New York City police officer who once had dreams of retiring to Florida.
In 1990, Mr. Dowd’s older brother, living in a veteran’s hospital in an advanced
stage of the disease, was strangled in his own restraints. But a year or so
later, when Ms. Moser wanted to do her sixth-grade science project on
Huntington’s, her mother recoiled.
“Why,” she demanded, “would you want to do it on this disease that is killing
Ms. Moser was left to confirm for herself, through library books and a CD-ROM
encyclopedia, that she and her brothers, her mother, her aunts, an uncle and
cousins could all face the same fate.
Any child who has a parent with Huntington’s has a 50 percent chance of having
inherited the gene that causes it, Ms. Moser learned.
Her mother, who asked not to be identified by name for fear of discrimination,
had not always been so guarded. At one point, she drove around with a “Cure HD”
sign in the window of her van. She told people that her father had “Woody
Guthrie’s disease,” invoking the folk icon who died of Huntington’s in 1967.
But her efforts to raise awareness soon foundered. Huntington’s is a rare
genetic disease, affecting about 30,000 people in the United States, with about
250,000 more at risk. Few people know what it is. Strangers assumed her father’s
unsteady walk, a frequent early symptom, meant he was drunk.
“Nobody has compassion,” Ms. Moser’s mother concluded. “People look at you like
you’re strange, and ‘What’s wrong with you?’ ”
Shortly after a simple DNA test became available for Huntington’s in 1993, one
of Ms. Moser’s aunts tested positive. Another, driven to find out if her own
medical problems were related to Huntington’s, tested negative. But when Ms.
Moser announced as a teenager that she wanted to get tested one day, her mother
insisted that she should not. If her daughter carried the gene, that meant she
did, too. And she did not want to know.
“You don’t want to know stuff like that,” Ms. Moser’s mother said in an
interview. “You want to enjoy life.”
Ms. Moser’s father, who met and married his wife six years before Ms. Moser’s
grandfather received his Huntington’s diagnosis, said he had managed not to
think much about her at-risk status.
“So she was at risk,” he said. “Everyone’s at risk for everything.”
The test, Ms. Moser remembers her mother suggesting, would cost thousands of
dollars. Still, in college, Ms. Moser often trolled the Web for information
about it. Mostly, she imagined how sweet it would be to know she did not have
the gene. But increasingly she was haunted, too, by the suspicion that her
As awful as it was, she admitted to Ms. Elio, her freshman-year neighbor at
Elizabethtown College in Pennsylvania, she almost hoped it was true. It would
explain her mother’s strokes of meanness, her unpredictable flashes of anger.
Ms. Moser’s mother said she had never considered the conflicts with her daughter
out of the ordinary. “All my friends who had daughters said that was all normal,
and when she’s 25 she’ll be your best friend,” she said. “I was waiting for that
to happen, but I guess it’s not happening.”
When Ms. Moser graduated in 2003 with a degree in occupational therapy, their
relationship, never peaceful, was getting worse. She moved to Queens without
giving her mother her new address.
Wanting to Know
Out of school, Ms. Moser soon spotted a listing for a job at Terence Cardinal
Cooke Health Care Center, a nursing home on the Upper East Side of Manhattan.
She knew it was meant for her.
Her grandfather had died there in 2002 after living for a decade at the home,
one of only a handful in the country with a unit devoted entirely to
“I hated visiting him growing up,” Ms. Moser said. “It was scary.”
Now, though, she was drawn to see the disease up close.
On breaks from her duties elsewhere, she visited her cousin James Dowd, the son
of her grandfather’s brother who had come to live in the Huntington’s unit
several years earlier. It was there, in a conversation with another staff
member, that she learned she could be tested for only a few hundred dollars at
the Columbia clinic across town. She scheduled an appointment for the next week.
The staff at Columbia urged Ms. Moser to consider the downside of genetic
testing. Some people battle depression after they test positive. And the
information, she was cautioned, could make it harder for her to get a job or
But Ms. Moser bristled at the idea that she should have to remain ignorant about
her genetic status to avoid discrimination. “I didn’t do anything wrong,” she
said. “It’s not like telling people I’m a drug addict.”
She also recalls rejecting a counselor’s suggestion that she might have asked to
be tested as a way of crying for help.
“I’m like, ‘No,’ ” Ms. Moser recalls replying. “ ‘I’ve come to be tested because
I want to know.’ ”
No one routinely collects demographic information about who gets tested for
Huntington’s. At the Huntington’s Disease Center at Columbia, staff members say
they have seen few young people taking the test.
Ms. Moser is still part of a distinct minority. But some researchers say her
attitude is increasingly common among young people who know they may develop
More informed about the genetics of the disease than any previous generation,
they are convinced that they would rather know how many healthy years they have
left than wake up one day to find the illness upon them. They are confident that
new reproductive technologies can allow them to have children without
transmitting the disease and are eager to be first in line should a treatment
“We’re seeing a shift,” said Dr. Michael Hayden, a professor of human genetics
at the University of British Columbia in Vancouver who has been providing
various tests for Huntington’s for 20 years. “Younger people are coming for
testing now, people in their 20s and early 30s; before, that was very rare. I’ve
counseled some of them. They feel it is part of their heritage and that it is
possible to lead a life that’s not defined by this gene.”
Before the test, Ms. Moser made two lists of life goals. Under “if negative,”
she wrote married, children and Ireland. Under “if positive” was exercise,
vitamins and ballroom dancing. Balance, in that case, would be important.
Opening a bed-and-breakfast, a goal since childhood, made both lists.
In the weeks before getting the test results, Ms. Moser gave Ms. Elio explicit
instructions about acceptable responses. If she was negative, flowers were O.K.
If positive, they were not. In either case, drinking was acceptable. Crying was
But it was Ms. Elio’s husband, Chris Elio, who first broached the subject of
taking care of Ms. Moser, whom their young children called “my Katie,” as in
“this is my mom, this is my dad, this is my Katie.” They should address it
before the results were in, Mr. Elio told his wife, so that she would not feel,
later, that they had done it out of a sense of obligation.
The next day, in an e-mail note that was unusually formal for friends who sent
text messages constantly and watched “Desperate Housewives” while on the phone
together, Ms. Elio told Ms. Moser that she and her husband wanted her to move in
with them if she got sick. Ms. Moser set the note aside. She did not expect to
‘It’s Too Hard to Look’
The results had come a week early, and Ms. Moser assured her friends that the
“Sex and the City” trivia party she had planned for that night was still on.
After all, she was not sick, not dying. And she had already made the dips.
“I’m the same person I’ve always been,” she insisted that night as her guests
gamely dipped strawberries in her chocolate fountain. “It’s been in me from the
But when she went to work the next day, she lingered outside the door of the
occupational therapy gym, not wanting to face her colleagues. She avoided the
Huntington’s floor entirely, choosing to attend to patients ailing of just about
anything else. “It’s too hard to look at them,” she told her friends.
In those first months, Ms. Moser summoned all her strength to pretend that
nothing cataclysmic had happened. At times, it seemed easy enough. In the
mirror, the same green eyes looked back at her. She was still tall, a devoted
Julia Roberts fan, a prolific baker.
She dropped the news of her genetic status into some conversations like small
talk, but kept it from her family. She made light of her newfound fate, though
often friends were not sure how to take the jokes.
“That’s my Huntington’s kicking in,” she told Rachel Markan, a co-worker, after
knocking a patient’s folder on the floor.
Other times, Ms. Moser abruptly dropped any pretense of routine banter. On a
trip to Florida, she and Ms. Elio saw a man in a wheelchair being tube-fed, a
method often used to keep Huntington’s patients alive for years after they can
no longer swallow.
“I don’t want a feeding tube,” she announced flatly.
In those early days, she calculated that she had at least until 50 before
symptoms set in. That was enough time to open a bed-and-breakfast, if she acted
fast. Enough time to repay $70,000 in student loans under her 30-year term.
Doing the math on the loans, though, could send her into a tailspin.
“I’ll be repaying them and then I’ll start getting sick,” she said. “I mean,
there’s no time in there.”
Finding New Purpose
At the end of the summer, as the weather grew colder, Ms. Moser forced herself
to return to the Huntington’s unit.
In each patient, she saw her future: the biophysicist slumped in his wheelchair,
the refrigerator repairman inert in his bed, the onetime professional tennis
player who floated through the common room, arms undulating in the startlingly
graceful movements that had earned the disease its original name, “Huntington’s
chorea,” from the Greek “to dance.”
Then there was her cousin Jimmy, who had wrapped papers for The New York Post
for 19 years until suddenly he could no longer tie the knots. When she greeted
him, his bright blue eyes darted to her face, then away. If he knew her, it was
impossible to tell.
She did what she could for them. She customized their wheelchairs with padding
to fit each one’s unique tics. She doled out special silverware, oversized or
bent in just the right angles to prolong their ability to feed themselves.
Fending off despair, Ms. Moser was also filled with new purpose. Someone,
somewhere, she told friends, had to find a cure.
It has been over a century since the disease was identified by George
Huntington, a doctor in Amagansett, N.Y., and over a decade since researchers
first found the gene responsible for it.
To raise money for research, Ms. Moser volunteered for walks and dinners and
golf outings sponsored by the Huntington’s Disease Society of America. She
organized a Hula-Hoop-a-thon on the roof of Cardinal Cooke, then a bowl-a-thon
at the Port Authority. But at many of the events, attendance was sparse.
It is hard to get people to turn out for Huntington’s benefits, she learned from
the society’s professional fund-raisers. Even families affected by the disease,
the most obvious constituents, often will not help publicize events.
“They don’t want people to know they’re connected to Huntington’s,” Ms. Moser
said, with a mix of anger and recognition. “It’s like in my family — it’s not a
Her first session with a therapist brought a chilling glimpse of how the
disorder is viewed even by some who know plenty about it. “She told me it was my
moral and ethical obligation not to have children,” Ms. Moser told Ms. Elio by
cellphone as soon as she left the office, her voice breaking.
In lulls between fund-raisers, Ms. Moser raced to educate her own world about
Huntington’s. She added links about the disease to her MySpace page. She
plastered her desk at work with “Cure HD” stickers and starred in a video about
the Huntington’s unit for her union’s Web site.
Ms. Moser gave blood for one study and spoke into a microphone for researchers
trying to detect subtle speech differences in people who have extra CAG repeats
before more noticeable disease symptoms emerge.
When researchers found a way to cure mice bred to replicate features of the
disease in humans, Ms. Moser sent the news to friends and acquaintances.
But it was hard to celebrate. “Thank God,” the joke went around on the
Huntington’s National Youth Alliance e-mail list Ms. Moser subscribed to, “at
least there won’t be any more poor mice wandering around with Huntington’s
In October, one of Ms. Moser’s aunts lost her balance while walking and broke
her nose. It was the latest in a series of falls. “The cure needs to be soon for
me,” Ms. Moser said. “Sooner for everybody else.”
A Confrontation in Court
In the waiting room of the Dutchess County family courthouse on a crisp morning
in the fall of 2005, Ms. Moser approached her mother, who turned away.
“I need to tell her something important,” Ms. Moser told a family member who had
accompanied her mother to the hearing.
He conveyed the message and brought one in return: Unless she was dying, her
mother did not have anything to say to her.
That Ms. Moser had tested positive meant that her mother would develop
Huntington’s, if she had not already. A year earlier, Ms. Moser’s mother had
convinced a judge that her sister, Nora Maldonado, was neglecting her daughter.
She was given guardianship of the daughter, 4-year-old Jillian.
Ms. Moser had been skeptical of her mother’s accusations that Ms. Maldonado was
not feeding or bathing Jillian properly, and she wondered whether her effort to
claim Jillian had been induced by the psychological symptoms of the disease.
Her testimony about her mother’s genetic status, Ms. Moser knew, could help
persuade the judge to return Jillian. Ms. Maldonado had found out years earlier
that she did not have the Huntington’s gene.
Ms. Moser did not believe that someone in the early stages of Huntington’s
should automatically be disqualified from taking care of a child. But her own
rocky childhood had convinced her that Jillian would be better off with Ms.
She told her aunt’s lawyer about her test results and agreed to testify.
In the courtroom, Ms. Moser took the witness stand. Her mother’s lawyer jumped
up as soon as the topic of Huntington’s arose. It was irrelevant, he said. But
by the time the judge had sustained his objections, Ms. Moser’s mother,
stricken, had understood.
The next day, in the bathroom, Ms. Maldonado approached Ms. Moser’s mother.
“I’m sorry,” she said. Ms. Moser’s mother said nothing.
The court has continued to let Ms. Moser’s mother retain guardianship of
Jillian. But she has not spoken to her daughter again.
“It’s a horrible illness,” Ms. Moser’s mother said, months later, gesturing to
her husband. “Now he has a wife who has it. Did she think of him? Did she think
of me? Who’s going to marry her?”
Facing the Future
Before the test, it was as if Ms. Moser had been balanced between parallel
universes, one in which she would never get the disease and one in which she
would. The test had made her whole.
She began to prepare the Elio children and Jillian for her illness, determined
that they would not be scared, as she had been with her grandfather. When
Jillian wanted to know how people got Huntington’s disease “in their pants,” Ms.
Moser wrote the text of a children’s book that explained what these other kinds
of “genes” were and why they would make her sick.
But over the winter, Ms. Elio complained gently that her friend had become “Ms.
H.D.” And an impromptu note that arrived for the children in the early spring
convinced her that Ms. Moser was dwelling too much on her own death.
“You all make me so happy, and I am so proud of who you are and who you will
be,” read the note, on rainbow scratch-and-write paper. “I will always remember
the fun things we do together.”
Taking matters into her own hands, Ms. Elio created a profile for Ms. Moser on
an online dating service. Ms. Moser was skeptical but supplied a picture.
Dating, she said, was the worst thing about knowing she had the Huntington’s
gene. It was hard to imagine someone falling enough in love with her to take on
Huntington’s knowingly, or asking it of someone she loved. At the same time, she
said, knowing her status could help her find the right person, if he was out
“Either way, I was going to get sick,” she said. “And I’d want someone who could
handle it. If, by some twist of fate, I do get married and have children, at
least we know what we’re getting into.”
After much debate, the friends settled on the third date as the right time to
mention Huntington’s. But when the first date came, Ms. Moser wished she could
just blurt it out.
“It kind of just lingers there,” she said. “I really just want to be able to
tell people, ‘Someday, I’m going to have Huntington’s disease.’ ”
‘A Part of My Life’
Last May 6, a year to the day after she had received her test results, the
subject line “CAG Count” caught Ms. Moser’s attention as she was scrolling
through the online discussion forums of the Huntington’s Disease Advocacy
Center. She knew she had 45 CAG repeats, but she had never investigated it
She clicked on the message.
“My mother’s CAG was 43,” it read. “She started forgetting the punch line to
jokes at 39/40.” Another woman whose husband’s CAG count was 47 had just sold
his car. “He’s 39 years old,” she wrote. “It was time for him to quit driving.”
Quickly, Ms. Moser scanned a chart that accompanied the messages for her number,
45. The median age of onset to which it corresponded was 37.
Ms. Elio got drunk with her husband the night Ms. Moser finally told her.
“That’s 12 years away,” Ms. Moser said.
The statistic, they knew, meant that half of those with her CAG number started
showing symptoms after age 37. But it also meant that the other half started
showing symptoms earlier.
Ms. Moser, meanwhile, flew to the annual convention of the Huntington’s Disease
Society, which she had decided at the last minute to attend.
“Mother or father?” one woman, 23, from Chicago, asked a few minutes after
meeting Ms. Moser in the elevator of the Milwaukee Hilton. “Have you tested?
What’s your CAG?”
She was close to getting herself tested, the woman confided. How did it feel to
“It’s hard to think the other way anymore of not knowing,” Ms. Moser replied.
“It’s become a part of my life.”
After years of trying to wring conversation from her family about Huntington’s,
Ms. Moser suddenly found herself bathing in it. But for the first time in a long
time, her mind was on other things. At a youth support group meeting in the
hotel hallway, she took her place in the misshapen circle. Later, on the dance
floor, the spasms of the symptomatic seemed as natural as the gyrations of the
“I’m not alone in this,” Ms. Moser remembers thinking. “This affects other
people, too, and we all just have to live our lives.”
Seizing the Day
July 15, the day of Ms. Moser’s 25th birthday party, was sunny, with a hint of
moisture in the air. At her aunt’s house in Long Beach, N.Y., Ms. Moser wore a
dress with pictures of cocktails on it. It was, she and Ms. Elio told anyone who
would listen, her “cocktail dress.” They drew the quotation marks in the air.
A bowl of “Cure HD” pins sat on the table. Over burgers from the barbecue, Ms.
Moser mentioned to family members from her father’s side that she had tested
positive for the Huntington’s gene.
“What’s that?” one cousin asked.
“It will affect my ability to walk, talk and think,” Ms. Moser said. “Sometime
before I’m 50.”
“That’s soon,” an uncle said matter-of-factly.
“So do you have to take medication?” her cousin asked.
“There’s nothing really to take,” Ms. Moser said.
She and the Elios put on bathing suits, loaded the children in a wagon and
walked to the beach.
More than anything now, Ms. Moser said, she is filled with a sense of urgency.
“I have a lot to do,” she said. “And I don’t have a lot of time.”
Over the next months, Ms. Moser took tennis lessons every Sunday morning and
went to church in the evening.
When a planned vacation with the Elio family fell through at the last minute,
she went anyway, packing Disney World, Universal Studios, Wet ’n Wild and Sea
World into 36 hours with a high school friend who lives in Orlando. She was
honored at a dinner by the New York chapter of the Huntington’s society for her
outreach efforts and managed a brief thank-you speech despite her discomfort
with public speaking.
Having made a New Year’s resolution to learn to ride a unicycle, she bought a
used one. “My legs are tired, my arms are tired, and I definitely need
protection,” she reported to Ms. Elio. On Super Bowl Sunday, she waded into the
freezing Atlantic Ocean for a Polar Bear swim to raise money for the Make-a-Wish
Ms. Elio complained that she hardly got to see her friend. But one recent
weekend, they packed up the Elio children and drove to the house the Elios were
renovating in eastern Pennsylvania. The kitchen floor needed grouting, and,
rejecting the home improvement gospel that calls for a special tool designed for
the purpose, Ms. Moser and Ms. Elio had decided to use pastry bags.
As they turned into the driveway, Ms. Moser studied the semi-attached house next
door. Maybe she would move in one day, as the Elios had proposed. Then, when she
could no longer care for herself, they could put in a door.
First, though, she wanted to travel. She had heard of a job that would place her
in different occupational therapy positions across the country every few months
and was planning to apply.
“I’m thinking Hawaii first,” she said.
Then they donned gloves, mixed grout in a large bucket
of water and began the