By Ellen Nakashima
Washington Post Staff Writer
Saturday, 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.
And he wants 99,999 other people to follow suit.
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."
He added: "We're all at risk for everything to some extent, and so we need to have a rich set of data and we need to be sharing that data until we get a much deeper understanding of what all the risk factors are, environmental and genetic."In the Lab
In Church's lab at Harvard Medical School in Boston, a contraption resembling a front-loading 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 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-to-consumer 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.
"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 gene-behavior 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.
"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.
"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.