Genome Database Will Link Genes, Traits in Public View
By Ellen Nakashima, Washington Post
October 18, 2008
BOSTON -- George Church wants to put his personal genetic blueprint online for all to
see -- the sequence of chemical bases that make him who he is, a lanky scientist of
Scottish ancestry who has dyslexia, narcolepsy and motion sickness.
The Harvard genetics professor's Personal Genome Project is an attempt to build the
only public genomic database that connects genes with diseases. With it, he believes,
scientists could correlate more easily many millions of genetic variants with medical and
other traits, from asthma to acne, eye color to perfect pitch.
If successful, he says, it would usher in an era of "personalized medicine" -- enabling a
consumer to order up his own genetic blueprint and know what diseases might lurk in his
future. That could allow him to change his lifestyle to try to avoid them. Or climb K2 now,
while he still can.
A better understanding of genes could lead to more effective drugs, proponents say.
Couples could learn what diseases might be in store for their children and decide not to
have them. Eventually, they say, scientists might even be able to alter the dangerous
genes.
But other people consider Church's vision the darker side of genetic knowledge. Such a
database could be used against the participants. Insurance companies might refuse to
sell them life, disability or long-term care coverage. A child could learn she faces a
terrible disease. In a more far-fetched but still possible scenario, a criminal could craft
synthetic DNA using someone's genetic code in the database and place it at a crime
scene to frame that person. In a broader context, people might draw spurious links
between genes and criminal behavior.
The database, a nonprofit venture, is scheduled to go online Monday, when Church and
up to nine other volunteers -- the "PGP 10" -- will release their genomic data and traits
profiles to the public. Then anyone, from a university researcher to a kid working in a
basement lab, will be able to tap into the data and create research applications much the
way that Facebook allows vendors to create game applications. It has enormous
potential to help consumers control their health, proponents say, but critics say the risks
outweigh the potential benefits.
"If people are concerned about what will happen, then they probably shouldn't be
involved," said Church, 54. "We are recruiting people who are willing to have their data
in the public domain because there's a pretty good chance that it will be public, whether
you like it or not. So if you recruit people who are okay with that, then it's less likely that
they'll be shocked and alarmed when it happens, if it happens."
But Stephen Mercer, a lawyer in Rockville who specializes in the intersection of DNA
and civil liberties, said the trend opens the door to touting associations not based on
sound science. "That's the real unstated danger here," he said, "that it will be a
launching pad for behavioral human genetics, in the search for genes that dictate
personality traits, coyness, anxiety, family conflict, sexual orientation."
Mercer said he could envision companies marketing genetic screening kits to
prospective parents who might consider aborting a fetus, much like in the science fiction
movie "Gattaca," which depicts a future in which humans are engineered for perfection.
"Why have a kid who's over-anxious?" he said. "Why have a kid who's too impulsive?
Why have a gay kid?"
As Church sees it, however, if people have their genes sequenced, more data will be
available for valid associations. More people will also be able to figure out what diseases
they are at risk for and take action, by changing their diet or lifestyle or by using
medication. With more disease-gene associations, advocates say, clinicians can make
earlier and more accurate diagnoses, and pharmaceutical companies can make more
effective drugs.
"This is what I consider one of the most practical things we can do," said Church, who is
6 feet 4 inches tall, a vegan and has had a heart attack. "We're treating people like one
size fits all, like anybody can work in an asbestos factory, anybody can eat peanuts,
anybody can take this new antibiotic. It's just not true."
In Church's lab at Harvard Medical School in Boston, a contraption resembling a frontloading washing machine sits on a table. The Polonator, which Church developed, can
analyze DNA from eight tissue samples at a time, sending to a computer billions of
combinations of A's, C's, T's and G's that denote a person's genetic makeup.
PGP will start by sequencing 1 percent, or 60 million base pairs, of each participant's
DNA, the portion called the "exome," which codes for the proteins that make the body
function. Eventually, Church would like to read out all 6 billion base pairs in an individual.
In another aisle of his lab, Xiaodi Wu, 20, a Harvard undergraduate, is working on his
thesis project, a software tool that Church calls the "Traitomatic." Wu taps a few keys on
his laptop, and a chart appears on the screen. A list of disease predispositions, ranked in
order of severity, appears for James D. Watson, the Nobel laureate who co-discovered
the double-helix structure of DNA. Watson, now 80, has gene variants that indicate an
increased risk for prostate cancer and Graves' disease.
Watson is one of only a handful of people in the world who have had their genome
sequenced and made public. But "just because a disease shows up on a list doesn't
mean you'll get it," Wu cautioned. "The chance you'll get it as compared to the general
population might be elevated by 1 percent or something minuscule like that."
Church particularly wants data from older people so he can see whether individuals who
are predisposed to certain diseases actually developed them. In fact, Watson, who is
chancellor emeritus at the Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y.,
has neither prostate cancer nor Graves' disease. While he said Church's effort is
important, he said the privacy risks probably outweigh the benefits to be gained.
"In most cases, it's not going to change people's lives," he said.
But Joseph Thakuria, 39, a medical genetics staff physician at Massachusetts General
Hospital in Boston, said the database offers promise for treating children with severe
developmental problems. For instance, a child with autism may have a mutation in any
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of 200-odd genes linked to autism or developmental delay. Tracking how children with a
specific autism gene respond to a particular therapy could help improve the treatment for
others, he said.
Perhaps one of the most useful results will be exploring how gene variants interact,
because the presence of one disease gene may be mitigated by the presence of another
gene, Thakuria said. It may also help in family planning or identifying disease proclivities
in a fetus "so parents can have the option to terminate or to prepare for the possibility of
having a child with a disability," he said.
A Market Emerges
As PGP's database of genetic variants and their associated traits grows, direct-toconsumer genetic screening companies expect to draw on it to give their customers a
fuller account of the secrets locked in their DNA. Church serves as a scientific adviser to
three of them, as well as to seven companies that make genome sequencing machines.
He says any fees he earns go into PGP.
One firm he advises is Knome, which he co-founded two years ago across the Charles
River in Cambridge, Mass. For $350,000, Knome will sequence a client's entire genome,
fly him to Boston from anywhere in the world -- some clients have flown in on their own
jets -- and spend a day reviewing a customized analysis of common and rare conditions
for which the client may be at risk.
PGP is likely to be "incredibly useful" to Knome, said Jorge Conde, the firm's president
and chief executive. "They're going to find more associations, which means we're going
to be able to provide our clients more information."
But the rush to exploit genetic research for commercial purposes raises red flags for
Deborah C. Peel, a psychiatrist and founder of Patient Privacy Rights.
THIS STORY
Genome Database Will Link Genes, Traits in Public View
Personal Genome Project
"Personalized medicine will be a nightmare that drives up costs and doesn't address the
sickest people or the most devastating illnesses," she said. "It is for-profit medicine at its
worst, with a very nice name and propaganda that appears to value individuals. I am not
opposed to making profits -- I am just for making profits in a way that does not destroy
the privacy or lives of others."
Even Thakuria has concerns that some companies may draw unjustified conclusions
from studies that have not been validated or are based on a small fraction of the
genome. "There doesn't seem to be a very good vetting-out process," he said. "And I
think this applies to almost every company right now offering this testing directly to the
public."
One of the largest concerns of privacy advocates and civil libertarians is how genebehavior links might be applied to large DNA databases assembled by law enforcement,
which in about a dozen states now include samples from people who have been
arrested but not convicted.
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"When you have 6 million samples in a criminal database and there are some genetic
markers that are claimed to [predispose someone to] substance abuse, mental illness
and impulsive behavior, then you're going to see the further mining of this information in
an attempt to classify and target groups of people as potential criminals," Mercer said.
"That's one of the big fears -- that this trend is a precursor to a movement toward
eugenics" -- the controversial idea of molding human heredity to bolster desired
characteristics or eliminate undesirable ones.
A number of studies have attempted to find genetic links to shyness, intelligence,
novelty-seeking and sexual orientation. But, said Mark Rothstein, director of the Institute
for Bioethics, Health Policy and Law at the University of Louisville School of Medicine,
"even if there is an association of varying degrees between certain genes and behavior,
genetics is not destiny. My concern is that there is considerable risk that the research
will be misused in a variety of legal and social contexts."
Rothstein raised other issues posed by genetic databases. Though the recently passed
Genetic Information Nondiscrimination Act bars employers and health insurers from
discriminating against a person because of genetic predispositions, the law does not
outlaw discrimination by life, disability and long-term care insurers, he noted.
But Henry T. "Hank" Greely, a Stanford law professor, said focusing on associations
alone misses the point. "If people understood that, for example, a 'violence gene' might
change a person's risk of engaging in violent behavior from 5 percent to 7 percent, they
would neither think about preventive detention nor think about eugenics," he said.
"There's nothing wrong with the tool, and it may turn out to be medically important.
What's wrong is the misunderstanding and misuse of the tool."
A Leap of Faith
The PGP, which began as little more than a conviction by Church that it could be done,
won approval this year from the Harvard University Institutional Review Board, whose
role is to ensure the safety of research subjects, to proceed with his plan to enroll
100,000 participants.
To sign up, a person must pass a 40-question exam that includes queries such as, "How
much genomic material exists in a typical human cell?'' He must decide whether he is
comfortable with the privacy risks, including the possibility that an insurer could peruse
his data. Church plans to require volunteers to obtain the consent of their first-degree
relatives, who also stand to be exposed by having a blood relative's DNA on view.
It was the review board's idea that Church become a participant.
"They actually felt I would get more involved," Church said. His wife reacted "very
cautiously" to the idea, he said. She suggested they go on a "listening tour" to talk to
other prospective volunteers and their families.
Eventually, Church's wife, genetics professor Ting Wu, and their daughter, now 17,
consented to his participation, he said.
If PGP is to work, Church said, people are going to have to make a leap of faith.
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"Perfect can be the enemy of the very good," Church said. "Just like when you go out
and buy a car. You don't wait until they have a perfectly safe car. You say, 'Okay, 30,000
people die per year in the United States from car accidents. I'm going to roll the dice.' "
Staff researcher Magda Jean-Louis contributed to this report.
Genome Fanatics to Post Own DNA Sequences on Web
Los Angeles Times, from the Associated Press
October 21, 2008
BOSTON -- A group of scientists and researchers fascinated with the human genome
said Monday they will post online their most private personal information -- their medical
records and DNA sequence of some of their own genes -- all for the sake of research.
Led by Harvard Medical School genetics professor George Church, nine people plan to
post their records and the DNA sequence of about one-fifth of their genes on the Web.
The participants also include Harvard psychology professor Steven Pinker and Dr. John
Halamka, chief information officer at Harvard Medical School. A tenth participant, Misha
Angrist, science editor at the Duke University Institute for Genome Sciences & Policy,
said he plans to make his medical records public, but is still deciding on whether to make
his sequencing information public.
Harvard said this is the first phase of a major initiative to make personal genome
sequencing more affordable and accessible.
The release is part of the "Personal Genome Project," which is designed to serve as a
resource for researchers investigating the genetic basis of diseases and other traits.
Members of the group received the protein-coding regions of their genomes Monday.
After reviewing the information with a doctor, they were given the option of sharing it with
the research community and general public by posting it on the project's Web site.
Participants discussed their decisions at a news conference at Harvard on Monday
afternoon.
Halamka said his results showed he could be at an increased risk for several diseases,
including prostate cancer and a neurological disorder that causes weakness and
numbness in the legs. He said knowing he has an increased risk could help him when he
has a physical examination.
"I think as a family we will now approach our care a little differently," he said.
Participants said they decided to make their information public to help medical research.
"I believe that there's a great advantage to each of us knowing our sequences, but it is
also to me inconceivable that absolute genetic privacy will be maintained," said Stanley
Lapidus, chairman and CEO of Helicos BioSciences Corp.
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Earlier this year, Church's project won approval from Harvard's ethical review board to
sequence and post the genes and records of 100,000 willing participants. Church later
asked nine people to participate in the first stage of the project.
On Tuesday, the Personal Genome Project's Web site will post the DNA sequences, cell
lines, and medical and non-medical traits of participants who agreed to disclose their
information. Anyone with access to the Internet can view the information.
Concerns about genetic privacy prompted Congress to pass the Genetic Information
Nondiscrimination Act, which prohibits insurers or employers from discriminating against
people based on their genetic information. The act was signed into law in May.
So far, the project has sequenced about 20 percent of the genome regions of
participants, but it will eventually scan all their genes.
Last year, DNA pioneers J. Craig Venter, president of a genetics research institute, and
James Watson, co-discoverer of DNA's molecular structure, made their genomes public
on scientific Web sites.
-----On the Web:
personalgenomes.org
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