George Church: The Future Without Limit

Geneticist George Church tinkers with DNA to fight disease, create new biofuels, and perhaps even resurrect extinct species.

In the future, George Church believes, almost everything will be better because of genetics. If you have a medical problem, your doctor will be able to customize a treatment based on your specific DNA pattern. When you fill up your car, you won't be draining the world's dwindling supply of crude oil, because the fuel will come from microbes that have been genetically altered to produce biofuel. When you visit the zoo, you'll be able to take your children to the woolly mammoth or passenger pigeon exhibits, because these animals will no longer be extinct. You'll be able to do these things, that is, if the future turns out the way Church envisions it—and he's doing everything he can to see that it does.

George McDonald Church is a big man, six feet five inches tall, with a full beard and a deep, reassuring voice. At his lab at Harvard Medical School in Boston, the 59-year-old molecular engineer supervises a team of 90 or so graduate students, postdocs, visiting scientists, and staff as they undertake cutting-edge science. They're manipulating DNA, RNA, and proteins—the basic tools of the genetics revolution—to accomplish futuristic tasks such as developing new medical therapies, creating biofuel technologies, and laying the groundwork for de-extinction.

As a consequence of the work Church has done in genetics, we know a lot more about him than you might expect. We know that he weighs about 246 pounds and that he has green eyes and blood type O. We know that he's suffered from dyslexia since he was a boy and narcolepsy since he was a teenager, had a heart attack in 1994, was treated for skin cancer in 2002, and underwent a colonoscopy in 2012. If you're curious, you can view images of his colon online.

We know all this—and much more, including the results of his brain scans, sleep studies, and the sequencing of his DNA—because Church believes that the benefits of sharing such personal data vastly outweigh privacy concerns. The possibility that someone might exploit the data to steal his identity or carry out some other mischief worries him far less than the idea that by withholding such information, he might be delaying the onward march of science.

The Facebook Generation

That's why in 2005 he launched the Personal Genome Project, with the goal of sequencing and sharing the DNA of 100,000 volunteers. With an open-source database of that size, he believes, researchers everywhere will be able to meaningfully pursue the critical task of correlating genetic patterns with physical traits, illnesses, and exposure to environmental factors to find new cures for diseases and to gain basic insights into what makes each of us the way we are. Church, tagged as subject hu43860C, was first in line for testing. Since then, more than 13,000 people in the U.S., Canada, and the U.K. have volunteered to join him, helping to establish what he playfully calls the Facebook of DNA.

"It's not for everyone," he says. "But I see a trend here. Openness has changed since many of us were young. People didn't use to talk about sexuality or cancer in polite society. This is the Facebook generation."

Church was still a teenager, he says, when he came up with the idea that everyone, as a matter of course, should have his or her genome sequenced—all six billion chemical letters that make up human DNA. If individuals were told which diseases or medical conditions they were genetically predisposed to, they could adjust their behavior accordingly, he reasoned. Although universal testing still isn't practical today, the cost of sequencing an individual genome has dropped dramatically in recent years, from about $7 million in 2007 to as little as $1,000 today. There are also now 2,000 or so genetic tests available to identify specific cancer genes and other rare genetic patterns as aids to prevention or treatment. Though their accuracy needs improvement, most of these wouldn't have been possible before 2000, when researchers first mapped the human genome.

As one of the scientists who helped launch that epic effort—the "moonshot of genetics," as he describes it—Church has made a career of defying the impossible. Propelled by the dizzying speed of technological advancement since then, the Personal Genome Project is just one of Church's many attempts to overcome obstacles standing between him and the future. "It's all too easy to dismiss the future," he says. "People confuse what's impossible today with what's impossible tomorrow."

The Wonder of Futurama

Church was a wide-eyed nine-year-old when he first saw the future. "It was bright and shiny," he says. "All the surfaces were smooth. Everything was less clunky."

It was the 1964-1965 New York World's Fair. Spread out over almost a square mile of Flushing Meadows Park in Queens, the international exposition celebrated the latest in technological wonders. At the IBM exhibit, a cabinet-size computer looked up information about dates that visitors wrote down on slips of paper. At the Bell Systems Pavilion, people were invited to try out the Picturephone—four decades before Skype or FaceTime. As they rode through the Futurama exhibit in the General Motors pavilion, young and old were treated to visions of colonies on the moon and hotels at the bottom of the sea.

As a restless fourth grader from Tampa, Florida, Church was dazzled by what he saw. Until then, he'd spent more time chasing turtles in the mud and weeds near his home than dreaming of robots and computers. But now the future beckoned. "It just struck me as the kind of place where we all deserved to live," he says. "And then I went back home to Florida, and I sort of waited for the future to arrive. And it didn't." Frustrated by being stuck in the mundane present but still inspired by what he'd seen, the boy made a decision that set his course as a man. "I realized that if I was going to relive that moment, I was going to have to help create it," he says.

At Duke University, where he earned a bachelor's degree in chemistry and zoology in only two years, he pursued his dream of shaping the future by studying RNA, or ribonucleic acid, a family of molecules that carry out essential tasks in the cell. As a graduate student at Duke working under Professor Sung-Hou Kim, he used x-ray crystallography to study the three-dimensional structure of "transfer" RNA, which decodes DNA and carries instructions to other parts of the cell. It was groundbreaking research, but Church spent so much time in the lab—up to a hundred hours a week—that he neglected his other classes. When he received an F in one course, he was dropped from Duke's biochemistry program. (As part of his full-disclosure campaign, Church has also posted online the associate dean's letter to him conveying the bad news.)

The Notion of Multiplexing

Enrolling in the Department of Biochemistry and Molecular Biology at Harvard that fall, Church kept pushing the boundaries of research by developing a new technique to map DNA with Professor Walter Gilbert, who would win a Nobel Prize in chemistry. Church also came up with an idea he called "multiplexing" to sequence dozens to millions of pieces of DNA simultaneously—processing them all in the same tube—rather than one at a time, which had been the accepted method. Eventually his technique revolutionized the study of DNA by exponentially reducing the cost of sequencing it. But it was almost eight years of starts and stops before Church was in a position to prove that the technique would work, a pattern of inspiration and persistence that became a creative habit.

"I'll drop something for a while, a year or maybe several years, and then pick it up again," he says. "I think that's the way successful innovators work. They keep juggling ideas, keeping them in the air, in the back of their mind, to inspire them or enable new recombinations."

Today, with faculty appointments at both Harvard and MIT, as well as management duties at the Broad Institute in Boston, which focuses on biomedical research, and the nearby Wyss Institute, which specializes in technology transfer to industry, Church juggles teaching duties as well as intellectual tasks. His wife, Chao-ting Wu, is also a professor of genetics at Harvard. Often Church is so absorbed in his work that he skips breakfast and lunch. Although he enjoys putting in lab time to conduct his own experiments occasionally, he devotes most of his energy to encouraging his team to innovate.

"A lot of people can't be bothered with innovation," he says. "It's a nuisance, in certain ways. It usually brings a lot of anxiety and other problems—the kinds of things that prevent the average person from setting aside the time and taking the risks." But for Church's lab, there's no alternative, he says. It's the only way forward.

"Very often, as I wander through life, I'll get that old feeling that I've come back from the future, and I'm living in the past," he says. "And it's a really horrible feeling."

A New Kind of Plastic Cup

At the beginning of his 2012 book Regenesis, which he co-authored with science writer Ed Regis, Church tells a story about a new kind of plastic cup. The cup made its debut at the John F. Kennedy Center for the Performing Arts in Washington, D.C., one night in 2009 to serve drinks to patrons during the intermission. If theatergoers had closely inspected the cups, they would have found a surprising label: "Plastic made 100% from plants."

The cups were made of Mirel, or polyhydroxybutyrate (PHB), a substance normally produced with petrochemicals. But this batch was manufactured at a factory in Clinton, Iowa, from genetically altered microbes and corn sugar. The microbes consumed the sugar and converted it into bioplastic in the same way that yeast turns malt and hops into beer. The result: a renewable source of biodegradable plastic that wasn't dependent on fossil fuels. It was just one example, Church wrote, of what was coming down the pike through the emerging discipline of "synthetic" biology.

The basic idea behind synthetic biology, he explained, was that natural organisms could be reprogrammed to do things they wouldn't normally do, things that might be useful to people. In pursuit of this, researchers had learned not only how to read the genetic code of organisms but also how to write new code and insert it into organisms. Besides making plastic, microbes altered in this way had produced carpet fibers, treated wastewater, generated electricity, manufactured jet fuel, created hemoglobin, and fabricated new drugs. But this was only the tip of the iceberg, Church wrote. The same technique could also be used on people.

"Every cell in our body, whether it's a bacterial cell or a human cell, has a genome," he says. "You can extract that genome—it's kind of like a linear tape—and you can read it by a variety of methods. Similarly, like a string of letters that you can read, you can also change it. You can write, you can edit it, and then you can put it back in the cell."

Consider someone with sickle-cell anemia, a normally incurable illness caused by the mutation of a single chemical letter on a specific gene. If you were to remove stem cells from the bone marrow of an individual with the disease, repair the defective gene in each cell, and then return the cells into the marrow to produce healthy blood cells, the individual would be cured, Church says. Similar techniques could be used to treat cystic fibrosis or Huntington's disease, which are also caused by mutations of a single DNA base pair, or even AIDS. In March, researchers at the University of Pennsylvania announced they had modified a gene in the immune systems of 12 HIV-positive patients to resist the virus. After treatment, half of the patients were temporarily taken off antiretroviral drugs. Of those, four showed a reduction of HIV virus in their bodies—one to undetectable levels.

In April, the Broad Institute, where Church holds a faculty appointment, was awarded a patent for a new method of genome editing called CRISPR (clustered regularly interspersed short palindromic repeats), which Church says is one of the most effective tools ever developed for synthetic biology. By studying the way that certain bacteria defend themselves against viruses, researchers figured out how to precisely cut DNA at any location on the genome and insert new material there to alter its function. Last month, researchers at MIT announced they had used CRISPR to cure mice of a rare liver disease that also afflicts humans. At the same time, researchers at Virginia Tech said they were experimenting on plants with CRISPR to control salt tolerance, improve crop yield, and create resistance to pathogens.

The possibilities for CRISPR technology seem almost limitless, Church says. If researchers have stored a genetic sequence in a computer, they can order a robot to produce a piece of DNA from the data. That piece can then be put into a cell to change the genome. "You don't even have to take the genome out of the organism," Church says. "You can change it essentially with the motor running. It's like you throw a piston into a car and it finds its way to the right place and swaps out with one of the pistons while the motor's running."

Church believes that CRISPR is so promising that last year he co-founded a genome-editing company, Editas, to develop drugs for currently incurable diseases. It was the latest of 13 biotech firms that he's helped found since 2005.

Hairy Elephant

Thanks to another groundbreaking technology developed in Church's lab, the notion of resurrecting extinct animals such as the woolly mammoth could also soon become a reality. Mammoths disappeared only about 3,400 years ago, and their remains—including bones, teeth, hair, skin, and fat—have been found across Siberia and Alaska. Using DNA from these remains, scientists have reconstructed a significant portion of the mammoth's genome, which they've discovered is closely related to that of the Asian elephant.

The easiest way to create a mammoth, Church argues, would be to start with an elephant's genome and gradually transform it into a mammoth's. Using the same cut-and-paste methods as those proposed for gene therapy, researchers would selectively replace elephant genes with key mammoth genes, such as those for woolly hair rather than stubby elephant bristles. A small team in Church's lab is already focusing on transferring three mammoth genes—for subcutaneous fat, cold-adapted hemoglobin, and long hair—to a living elephant cell line. This process may be accelerated by what Church calls MAGE technology (multiplex automated genomic engineering), which some have nicknamed the "evolution machine." Rather than carrying out substitutions one at a time, MAGE allows researchers to simultaneously introduce new genetic material on a wholesale basis. The practical result, Church told a group at National Geographic last year, could soon be "a hybrid elephant that has the best features of modern elephants and the best features of mammoths."

Although it would be significantly more difficult to achieve, and very likely more controversial, Church says, something similar could be done with DNA from Neanderthals, who disappeared about 30,000 years ago. Starting with a stem cell genome from a human adult, you could gradually reverse-engineer it into something like that of a Neanderthal. What would be the purpose? Perhaps to encourage different ways of thinking, Church suggests. Or to gain some useful traits from the Neanderthal immune system. Most Europeans and Asians already possess Neanderthal genes—up to 4 percent of their DNA. What else could humanity gain by borrowing from the Neanderthal genome?

Playing God?

Manipulating microbes. Tinkering with DNA. Bringing species back from the dead. Many of the wonders Church envisions for the future make other people extremely nervous. What if a mutant virus were to escape from the lab? What if bioterrorists were to get their hands on equipment to synthesize a disease like polio? How does Church justify such risks? What does he say to those who accuse him of trying to play God?

"Well, that sounds religious at first, but what most people mean when they say that is that you're doing something you're not qualified to do. That nobody has a sufficiently high knowledge to do such things without risk."

That may be true, he admits. But he says people should acknowledge that 1) nothing anyone does is without risk, and 2) doing nothing also entails risk. "There's a dark side to every technology," he argues. Cars kill 33,000 people a year in the United States, but that doesn't discourage people from driving or riding in cars. "New technologies always have a higher ratio of scary stories associated with them because they're still unknown." Making a new technology safe and effective doesn't mean making it perfectly safe and perfectly effective, he adds. "It means making it safer and more effective than whatever else is out there."

What scares people the most is the idea that scientists are shooting from the hip, Church says, or that they're about to run off a cliff and take everybody with them. "But that's what good safety engineering is all about, whether it's drugs or cars or engineering living systems. It's not playing God. It's engineering. It's what humans do. It's what distinguishes us from most other animals. We do things, and we do them on a bigger and bigger scale."

No one can predict all the challenges we'll face in the future, as individuals or as a society, Church says. But there's one thing he's sure of, and has been since he was a boy: "The best way to predict the future is to change it."

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