The first phase of George Church’s Personal Genome Project is underway. Earlier this month, the last of the first ten volunteers had his blood drawn for the project, which aims to sequence all the exons — or about 1 percent of the genome — of these individuals and correlate their sequence information with their medical records and other phenotypic information.
Nine of the 10 volunteers, who met each other for the first time in Boston two weeks ago, have agreed to make their names public (see In Sequence 7/24/2007, and spoke to In Sequence recently about their motivation for joining and their expectations for the project. Among them are five entrepreneurs, two university professors, a science writer, four medical doctors, and four PhDs. Eight of the volunteers are of European descent and one is African-American. Seven are men and two are women.
“We were not looking for celebrities,” Church told In Sequence last week. “We were looking for people who could figure out what they were getting into, and would be able to communicate all of the risks and benefits to other people.”
These ten, which comprise PGP1, will help prepare for the second phase of the project, during which Church, a professor of genetics at Harvard Medical School, and his colleagues aim to enroll 100,000 participants.
The project has already begun generating data for the first 10 participants: So far, the researchers have created SNP chip data for the first few samples, and have made sequencing libraries from their DNA, according to Church.
The PGP researchers are planning to use a high-throughput sequencing platform that is under development in the Church lab and is based on Church’s polony sequencing technology (see In Sequence 6/26/2007).
The volunteers will also fill out questionnaires about their phenotypic information, including physical data like height, weight, and hair color; medical information; as well as other characteristics that are known or suspected to have a genetic component. Those could include, for example, whether someone is a morning or evening person, whether they describe themselves as cheerful or grumpy, or whether they can roll up their tongue. A headshot photograph will also be part of the data collected.
Church and his colleagues aim to publish a description of the project and some preliminary results this fall, followed by the 1-percent genome of all 10 subjects by next February.
In parallel, starting within the next few months, they plan to launch the second phase of the project, or PGP2, which aims to enroll up to 100,000 participants and will probably also include the first 10 subjects.
The scope of sequencing for PGP2 will ultimately depend on the number of volunteers for that phase of the project, Church said. “If it turns out it’s hard to get people to do this, then we will be motivated to do a higher fraction of the genome,” he said. “If I had a choice between 100,000 people at 1 percent, and 1,000 at 100 percent, I would probably take the 100,000 people, and get better statistics.” Also, Church believes that the exons covered by the 1-percent-genome will cover about 98 percent of the phenotypic consequences.
PGP2, which is funded by private donors and income from Church’s patents, will be open to subjects worldwide. The study will mostly seek people above the age of 40 or 50, because they are likely to have a more extensive disease history that can be correlated with their genes. “By the time you are old, you have probably experienced the disease that is going to kill you, even if you are healthy,” Church said. The researchers will also recruit subjects with specific diseases if a community or funding agency asks them to do so.
Contrary to most other medical studies, the PGP does not promise its participants that their identities will be kept private, because the medical and genetic data they reveal may identify them. “That’s the important difference,” Church said. “Almost every other study says it’s unlikely that [your identity] will get out. In our case, we say, it is likely.”
The genetic data generated for the first 10 volunteers will be shared in phases. Initially, it will only be available to a small number of researchers as well as to the volunteers themselves, who at that point decide whether to make it available to a broader set of researchers. After that, the plan is to make the data later available to the general public. Nine of the volunteers have agreed to do that, and to attach their names to the data.
Church expects that the data will be of interest to many researchers, for example, experts in genetic association studies. The 10 initial PGP subjects have agreed to be contacted for studies of particular phenotypes in the future, as will the incoming volunteers. “We are hoping that the PGP will interact with lots of other projects and enable them to have a cohort of people that have been consented for multiple studies,” he said.
Some researchers believe that having the names of individuals, especially if they are well-known, attached to their data may skew the analysis. “It just seems to be inviting subjective, rather than objective, analyses,” said Jonathan Eisen, an evolutionary biologist and a professor in the GenomeCenter at the University of California, Davis.
Also, because the subjects of PGP2 will be selected at random and are unrelated, the analysis is going to be very complex. “It’s a different type of thing than the standard genetic studies” that often involve detailed information from several generations of families, said Eisen. “I am not sure if it’s going to be better than doing a case-controlled trial of some particular disease, but this is going to provide a background of genetic and phenotypic information that will help people design more careful studies,” he said.
Genomic Guinea Pigs
When it comes to learning new facts from his own genome, Church, who is one of the ten volunteers, said that he does not expect much initially, a sentiment that he shares with almost all of the other participants. “I think my expectations will rise as the number of datasets come in. Right now, I can only learn what’s in the scientific literature [already].”
In fact, all of the publicly known participants seem to think of themselves more as guinea pigs, or pioneers, testing the waters for the crowds that will follow, and serving scientists and their studies.
“I hope someone will learn something from mine,” said Esther Dyson, an angel investor in IT and healthcare startups and chair of EDventure Holdings.
She also wants to show others that despite the risks involved in making one’s genome public, the information itself is nothing to be afraid of. “My genome alone is not going to kill me. It’s not scary information in itself,” she told In Sequence.
For John Halamka, chief information officer of Harvard Medical School and a physician by training, one of the primary reasons for joining was his interest in privacy, and how clinical data is stored and represented. The only way to find out was to make himself available, he said. “I hope that by donating this dataset for all, that the ten of us will at least give folks some early data to start thinking about how we might use such data in the future for personalized care.”
For example, people need to learn how to ensure that the data is not altered, damaged, or accidentally erased, and how to keep it private.
“To me, the value is in the journey, not the destination,” Halamka said. “I am not that interested in discovering whether or not I am a candidate for early Alzheimer’s.” Nevertheless, he would like to find out if he is susceptible to certain diseases, so he can take preventive measures, if possible.
Other participants agree. “We all know that we are going to die; we don’t know when, we don’t know from what. So how does it change one’s life if one learns that one is at a higher risk for this or that?” said Stan Lapidus, CEO of Helicos BioSciences, which will soon launch its own next-generation sequencing technology.
Lapidus decided to volunteer because he wants people to start thinking about genomic data today. “There are many ways that genomic data can be used constructively, or maybe not so constructively, but they will be used anyway,” he said. “We have to recognize that the era of the $1,000 genome is so close to being here that we might as well begin the public discourse about what the appropriate boundaries are.”
“If I had a choice between 100,000 people at 1 percent, and 1,000 at 100 percent, I would probably take the 100,000 people, and get better statistics.”
To Misha Angrist, a science editor at the Duke Institute for Genome Sciences and Policy, it was less practical considerations than making his own genome more tangible. Angrist, who has a PhD in genetics, said he pipetted many DNA samples over the years, “and it was still always kind of an abstraction. Maybe I am naïve, but I’d like to think that having a look at my own genome might make it less of an abstraction.”
Angrist said that he plans to write about the project, which also factored into his decision to participate. “I think it’s much more interesting to write about something from the inside, as a participant observer.”
Making the genome more relevant was also the motivation for Rosalynn Gill-Garrison to participate. She is a co-founder and CSO of Sciona, a company that gives health and nutrition advice based on genomic and other information. “The human genome, for the average man, has not a lot of meaning,” she said. By setting an example, she wants people to get comfortable with understanding their DNA and show them “that genes don’t determine their fate.”
“From my standpoint, knowledge is power,” she said. “If I have information, it helps me take preventive measures.”
“I am hoping to use this information to help guide my own personal healthcare,” said Keith Batchelder, founder and CEO of Genomic Healthcare Strategies, a consulting firm, who also has a medical degree. “But it’s just one component of my personal medical record. It’s one piece of information that should be evaluated along with whether I smoke, exercise, what my cholesterol level is.” Batchelder already keeps his own electronic medical record, and wants to add his genome sequence to that.
Other participants are at the other end of the spectrum. James Sherley, an adult stem cell biologist with MD and PhD degrees, and until recently a professor at MIT, said his main motivation to join was his interest in designing epidemiology studies, not learning about his own genome. In fact, until tests for certain disease risks become more specific, he might not even want to learn about his genome. “I don’t really want to spend my future worrying about something that I really can’t know about for sure,” he said. “There are going to be a lot of false positives in the genome sequence.”
Most participants said they discussed the project with some of their immediate relatives prior to signing on, including children, siblings, or parents, all of whom share some of their genome. Though none said they were seeking explicit permission, they said their relatives had no strong objections.
Kirk Maxey’s genome data could potentially be of interest for a large number of people. In the past, he was a semen donor, and he said the sperm bank failed to keep track of the number of donor children he helped generate. “If [George] does me, he will also be doing 50 percent of 200 other people, possibly,” he said. Maxey, who is the CEO of Cayman Chemical and a doctor by training, also runs a non-profit institute that connects children of semen donors to their biological fathers.
When it comes to the risks associated with laying one’s genome open in public, most of the participants are not terribly worried.
The consent form lists a number of risks, they said, including losing health insurance or employment, identity theft, or having someone plant one’s DNA at a crime scene.
While participants do not dismiss these risks altogether, they did not prevent them from signing up. “If I thought that they were huge risks, I would not be doing this study,” Church said. “Instead of deciding whether they are risks or not in advance, we constantly monitor them.”
Sherley said there is another reason he is excited about the study: the cell line that will be established from participants’ blood cells can live on forever in the lab. “That’s just a remarkable opportunity,” he said. “Even if you don’t have children, your genome can live on.”