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Before I sat down to interview George Church, Harvard University geneticist and biochemist, Duke University
alumnus (’75), Duke dropout (’76), and technological and cultural visionary, I thought I’d do a little research on him.
This was a mistake.
It is impossible, it turns out, to do “a little research” on George Church. Type his name into Google and you get not so much a flow of information as a tsunami; practically everything you could ever want to know about him is publicly available. Would you like to see the letter Duke sent him when he flunked out of his biochemistry graduate program? It’s scanned and posted on his website. Would you like to read his genome—every last A, T, G, and C of it? You can find that online, too, along with a link to his medical records and a list of conditions he has or has had: “heart attack, carcinoma, narcolepsy, dyslexia, pneumonia, motion sickness.” If knowing Church’s genetic signature isn’t enough, his website also features a scan of his literal signature, complete with loopy flourish at the end. It listed his Social Security number, too, until a couple of years ago, when his wife told him it might be a good idea to keep at least a few things to himself. Even in the Facebook/Twitter/Tumblr era, most people don’t put highly personal details like this—especially biological ones, such as medical records and genetic data—out for the world to see. But for Church, the personal is professional. All this openness is part of an experiment he’s running called the Personal Genome Project (PGP), in which volunteers are having their DNA sequenced and making the resulting genotypes, along with relevant details about their lifestyles and medical histories (a.k.a., phenotypes), known to anyone who’s curious.
The point is to provide a preview of a future when many people know what’s in their own genes—a future that will be possible largely because technology invented by Church and others has made genome sequencing much cheaper than it used to be. (In addition to his day job as a Harvard genetics professor, Church advises or has founded more than twenty biotech firms.) The first sequenced human genome cost $3 billion. Today, a sequence can be had for about $10,000, and in the near future, it will cost less than $1,000. This new future will be an astonishingly productive time for medical research, as scientists begin to sift through and compare cheaply obtained genomes to elucidate why some people get sick and others stay healthy. But it will also be a time of shifting ethical and legal norms about biology and identity, and there may be new risks: of genetic information escaping from supposedly secure databases and winding up on the Web, of insurance companies trying to use it against patients, of private data becoming suddenly, irrevocably public.
So Church is trying to figure out what this new society might look like by simulating it in miniature with his band of volunteers
and, in the grand tradition of self-experimentation, himself. All that personal information of his is on the Web because he’s PGP Subject No. 1. “George is the rare practicing scientist who looks outward,” says Misha Angrist, an assistant professor at the Duke Institute for Genome Sciences & Policy, who is PGP Subject No. 4 (yes, his genome and medical data are on the Internet, too). “There aren’t a lot of people developing the technology who are also thinking so far downstream about what will be done with it.”
But let’s go upstream for a moment, back to Church’s time at Duke—because in a sense, that’s where all this started. Church was not an ordinary student. A computer prodigy as a child, he finished his undergraduate degree magna cum laude in two years and went straight into graduate studies. He found himself so fascinated by emerging tools for studying and visualizing molecules that soon he was spending about 100 hours a week in the lab and not nearly enough hours in class. Some of his mentors “tried to argue that I was somehow special,” he says, but administrators drew a hard line: “They said, ‘Yeah, everybody’s special.’ I didn’t particularly hold it against anybody, but I guess I felt like, ‘Well, I’m doing science anyway; what difference does it make if I don’t always go to class?’ That was my immaturity showing.” And so came the letter (“suitable for framing,” Church notes on his website) informing him that he had failed a course and would have to leave campus: “We … hope that whatever problems or circumstances may have contributed to your lack of success inpursuing your chosen field at Duke will not keep you from successful pursuit of a productive career.”
There was no need to worry. Church had already sown the seeds of his productive career during those 100-hour weeks at the bench, developing software for visualizing the structures of tiny molecules of RNA, the complement to DNA that, among other tasks, helps it make protein. (The software is still in use today.) He knew exactly where he wanted to go next: the lab of Walter Gilbert, a Harvard biochemist who would soon win the Nobel Prize. With Gilbert, Church developed a machine that could sequence large amounts of DNA—that is, discern the order of the four chemical “letters” or nucleotides (A, T, G, and C for adenine, thymine, guanine, and cytosine) that make it up.
DNA is an instruction manual for the body’s most fundamental processes. Variants, or tweaks in the order of the DNA letters—a change of an A for a G, say, or the loss of a stretch of letters on a given
chromosome—are a little like typos in that manual. Sometimes they don’t make any difference; the body can still “read” what it’s supposed to do. Other times, the typos result in the manufacture of proteins that don’t perform their biological jobs correctly. Variants can also cause the body to ramp up or dial back the production of many thousands of chemicals crucial to its function. This is how genes cause disease, influence behavior, and, to some degree, make us who we are as individuals. By comparing people’s genetic readouts—especially by lining up lists of hundreds of thousands of genes in many people, side by side, and looking for variants that appear in some people but not in others—scientists can start to figure out why, at the biochemical level, those people differ from each other.
When Church was first developing his technology, this sort of comparison wasn’t feasible. Scientists could read DNA, but
only small stretches of letters—sentences and paragraphs, not chapters, and certainly not entire manuals. It was slow, painstaking work that had to be done by hand. Church and Gilbert’s automating technology (and a similar method called
Sanger sequencing that would eventually overtake it) made it possible to imagine reading DNA on a large scale—to dream not of sentences but of books.
By now it was 1984, and a lot of other people were thinking about the possibilities in the human genome. Among them
were researchers at the U.S. Department of Energy, who that year summoned a small group of scientists—including Church, by far one of the youngest—to Alta, Utah, to discuss the prospect of estimating the rate at which genetic mutations accumulate in the average person under normal circumstances. (They were concerned that the rate would be higher in Japanese civilians who had survived atom-bomb attacks.) Making such an estimate is “barely possible” even today, says Church, because to reach statistical significance requires huge sets of genetic data from thousands and thousands of people, amounts of data that are just now starting to become widely available. It was an unthinkable goal in 1984.
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