On Thursday, James Watson was handed a DVD containing his entire genome, sequenced in the past few months by 454, a company based in Branford, CT, that’s developing next-generation technologies for efficiently reading the genome. At a cost of $2 million, 454 sequenced Watson’s genome for roughly an order of magnitude less than it would have cost using traditional machines. While this is still too expensive for the average Joe, experts say that the advance marks a major milestone toward personal-genome sequencing–and more-personalized medicine–for all.
“We’ve heard people talking about personalized medicine for the last year or two, but this is the first concrete incarnation of that whole era,” says George Weinstock, codirector of the Human Genome Sequencing Center at Baylor College of Medicine, in Houston. Scientists at Baylor collaborated on the genome project.
The $2 million and two months that it took to sequence Watson’s genome is a far cry from the more than ten years and $3 billion required for the Human Genome Project’s reference genome, released in 2003. Scientists ultimately hope to bring the cost down to less than $10,000, a target price that many believe will be the turning point in genomic medicine. At that price, many people could afford to have their genomes sequenced, and doctors could then use that data to give their patients more-personalized medical advice.
At a press conference at Baylor on Thursday announcing the completion of the genome, 454’s founder, Jonathan Rothberg, compared the company’s sequencing innovations with the technological advances that shrank computers to a size small enough for personal use. 454’s machines run the sequencing reactions on chips smaller than a playing card, drilled with 800,000 tiny holes. Each chip can run hundreds of thousands of sequencing reactions in a single experiment, compared with the 96 reactions possible when scientists initially sequenced the human genome. (See “Sequencing in a Flash.”)
While Watson’s genome represents a landmark in human sequencing and will be the subject of extensive research, it’s unlikely to be immediately useful to the geneticist on a personal level. Scientists did not find any of the hot-button mutations that guarantee that Watson would develop a certain disease. (Given that Watson has made it safely into his late seventies, this is relatively unsurprising.) They did, however, identify several mutations that boost the risk of cancer, including one linked to breast cancer. “I’ve had basal-cell carcinoma since the age of 28,” Watson said at the press conference. “Whether there is any connection, I don’t know.” Adding that his sister had suffered from serious breast cancer, he said, “I take comfort in the fact that it largely affects women, and that I don’t have any daughters. If I did, I would tell them to immediately check if they had [that mutation].”
Scientists also identified several hundred other interesting mutations–genetic variations that might affect the function or expression of a gene. While many mutations of this type have no observable effect,25 of Watson’s variants have been linked to some phenotypic effect in other studies, says Richard Gibbs, director of Baylor’s sequencing center. “But none have obvious health implications,” he says.
Watson’s genome will be difficult to interpret until scientists have gathered a larger database housing hundreds or thousands of people’s genomes, along with their personal characteristics, medical histories, and other information. That information will allow geneticists to correlate specific variations with different medical and more-general attributes, such as musical skill or athletic ability, ultimately giving a new level of meaning to the genome.
Watson’s genome, which is being deposited in a public database, is unlikely to remain alone for long. Illumina, a San Diego-based technology company that acquired 454’s rival sequencing company, Solexa, earlier this year, plans to sequence the genome of one of the people who contributed DNA to the HapMap project, an effort to catalogue human genetic variation. (See “A New Map for Health.”) The National Institutes of Health (NIH) is also planning a personal genome project: it aims to sequence the genomes of 100 different people in the next two years. NIH scientists are currently debating whose genomes would prove most useful to the research community. People included in the HapMap project, which focused on populations in Nigeria, China, Japan, and Utah, are likely candidates. (Craig Venter, a fellow genomic celebrity who pioneered Celera’s human genome project, previously revealed that he was the subject of that effort. His DNA now resides in a publicly funded genetic database, and according to the journal Nature, he soon plans to publish a paper describing it.)
454 also aims to create a longer list of personal genomes. Michael Egholm, vice president of molecular biology at 454, predicts that the company will reach the $100,000-genome point within the next year, which he says will be a turning point at which scientists can afford to sequence hundreds of genomes for research purposes. The next step will be the $10,000 genome, which should bring the company within reach of the X Prize Foundation’s $10 million award, announced last October, for the first privately funded team that can sequence 100 human genomes in 10 days. (See “The X Prize’s New Frontier: Genomics.”) “The goal is to make human sequencing routine,” says Egholm. “Someday in the future, every human will have their DNA sequenced, probably at birth.”
Watson’s case also brings back to the forefront many of the ethical issues surrounding the genomic age. Rothberg and others picked Watson as the subject of their first personal genome partly as an homage to a genetic pioneer, but also because, as a geneticist, he is intimately acquainted with the medical and ethical quandaries likely to arise from learning about one’s genome and making it publicly available. For example, someone might find out that she has the genetic variant for a largely untreatable or unpreventable disease, such as Alzheimer’s. Watson, who has a family history of Alzheimer’s, has said that he does not want to know if he carries a specific variation known as APOE4 that’s linked to increased risk of the disease.
One of the public’s biggest worries about personal genomics is the possibility of genetic discrimination when applying for a job or trying to get health insurance. Various states have legislation preventing this practice, but a corresponding federal bill has been languishing in Congress for years. Peter Traber, Baylor’s president, said at the press conference that he hopes the completion of Watson’s genome will spur passage of that bill.
Watson said he didn’t think too much about the contents of his genome in the interim between giving a DNA sample and getting the results. “I knew I was risking possible anxiety when I saw it,” he said. “But it’s much more likely that if I don’t sleep at night, it’s due to thinking about Iraq.”