$1,000 for Your Genome?
Imagine if doctors could tell you what diseases you're most susceptible to before you get sick -- and if scientists could create medicines to fit your personal genetics. George Church sees that day dawning.
When scientists sequenced the human genome in 2003, George Church let everyone else sing their praises. He was as thrilled as any other geneticist, but he rued the cost of completing the joban estimated $3 billion. No individual, of course, was going to get his or her own genome sequenced at that price. And few could today, now that the estimated cost has dropped to $20 million. "I'm very frustrated by that," Church says.
To those in the gene business, his frustration is understandable. While decoding the -human genome provides a map of the human race's DNA, it does not reveal much about yours or mine in particular. But imagine if it did. With individual genetic maps, we could not only know more about what makes each of us strong or weak, healthy or sick, but we'd each be able to see which diseases we're most vulnerable to and work to minimize the risks. Medicines might be designed to fi t personal genetics. Indeed, with such intimate knowledge of our biology, our understanding of human nature might change.
"It's like going through life without a mirror, and then suddenly being able to have one," says Church, a professor of genetics at Harvard Medical School and the director of the Lipper Center for Computational Genetics. "Imagine all the self-knowledge you could have."
Church, 54, a big, bearded man with an intense curiosity and friendly demeanor, helped launch the Human Genome Project in the early 1980s. Now, he wants to dramatically scale down the technologyfrom a national effort on the order of a moon landing to something as routine as a cholesterol check. Church's goal: to be able to decode an individual's DNA for about the cost of a personal computer, $1,000. And to do it by 2008.
Recently, Church reached a benchmark in his quest. In September, he reported decoding the genome of E. coli bacteria at one-ninth the conventional cost and 1/10,000th the error rate.
When scientists first decoded the 3.2 billion base pairs of human DNA those letter-coded chemicals that serve as our biological templatesthe material they deciphered was a composite of genes from 10 people. The result taught scientists a lot about humanity in general but very little about any individual. While nearly all DNA is identical from one person to the next, about 0.1 percent makes us different, with blue eyes or a risk for breast cancer. And there lies the challenge.
The only way to understand those variations is to compare the DNA from thousands or even millions of people and pick out the tiny differences. And the only way to do that is to develop a process that millions of individuals can afford. Church calls that quest "my own personal white whale."
Church sped through Duke University in two undergraduate years and earned a doctorate from Harvard in biochemistry and molecular biology. "What distinguishes George is how multidisciplinary he is," says Robi Mitra, a former student of Church's and now an assistant professor of genetics at Washington University in St. Louis. "His lab is one of the few places where you'll find microbiologists, mathematicians, and chemists all working together."
Today, Church lives in Brookline with his wife and teenage daughter. On a typical day, he gets to the lab around 9 a.m. to talk research with students and postdoctoral fellows. He meets his daughter after school and works from home in the evening. As a hobby, father and daughter raise hinge-backed tortoises. But at his day job, Church is interested in speed.
Church knew that a key to making gene sequencing fast and affordable lay in miniaturizing the process. He coats a slide with millions of microscopic beads, each impregnated with chemicals that light up when exposed to DNA base pairs. A digital camera fitted to a microscope photographs the pattern, and software decodes the results. His process is more than 250 times faster than conventional technology. In short, rather than take seven years to sequence the human genome, Church's machines can theoretically do it in less than a week. He says "theoretically" because he and his students have only decoded the DNA of E. coli, which is 1/1000th the size of the human genome. Based on his current costs, he thinks he could decode a human genome for about $2.2 million.
Meanwhile, at least half a dozen well-funded labs across the country are shooting for that $1,000 target. One, a Connecticut firm called 454 Life Sciences that runs a somewhat different microscopic technology, rivals Church's so closely that no one can predict who will reach the goal first.
One day, Church says, you will give blood at your doctor's office and get your DNA readout on, say, a DVD. "Your doctor could use software to scan through your genome and pick out all the alarm signals," Church says. "He might say, 'Let's do a blood test,' or maybe a colonoscopy a decade ahead of schedule."
At the same time, some worry that genetic information could be misusedby employers, insurance companies, or even identity thieves. "We have big issues in terms of privacy, disclosure, and use," says Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University.
Church, who believes that society will sidestep such hazards, sees the promise of understanding not only our diseases, but ourselves. "Of course, not everything is genetic," he says. "This will be a way to disentangle the whole nature-nurture thing." There's no end, he says, to the discoveries to be made. Hence his frustration. He knows that, as with computers, the treasures of DNA will only be realized when the technology to reveal them becomes smaller and cheaperin other words, personal.