George Church towers over most people. He has the long, gray beard of a wizard from Middle-earth, and his life’s work—poking and prodding DNA and delving into the secrets of life—isn’t all that far removed from a world where deep magic is real. The 63-year-old geneticist presides over one of the largest and best-funded academic biology labs in the world, headquartered on the second floor of the massive glass and steel New Research Building at Harvard Medical School. He also lends his name as an adviser or supporter to dozens of projects, consortiums, conferences, spinouts, and startups that share a mission to push the outer edge of everything, from biorobotics to bringing back the woolly mammoth. And on a steamy August morning last summer, he wants to talk to me about the outer edge of my life.
Church is one of the leaders of an initiative called the Genome Project-Write, or GP-Write, which is organizing the efforts of hundreds of scientists around the world who are working to synthesize the DNA of a variety of organisms. The group is still debating how far to go in synthesizing human DNA, but Church—standing in his office in a rumpled sport coat, behind the slender lectern he uses as a desk—says his lab has already made its own decision on the matter: “We want to synthesize modified versions of all the genes in the human genome in the next few years.”
His plan is to design and build long chains of human DNA, not solely by cutting and pasting small fixes—a now-routine practice, thanks to recent technologies like Crispr that let scientists edit DNA cheaply and easily—but by rewriting critical stretches of chromosomes that can then be stitched together with a naturally occurring genome. If they succeed, it will be a breathtaking leap in ambition and complexity from the genomes of bacteria and yeast that scientists up until now have worked to synthesize. “What we’re planning to do is far beyond Crispr,” Church says. “It’s the difference between editing a book and writing one.”
In writing the book, Church hopes to bend the human narrative to his will. By replacing select nucleotides—the ACGTs of life, which are scattered throughout the chromosomes—and changing, say, a T to an A or a C to a G in a process called recoding, Church envisions being able to make cells resistant to viruses. “Like HIV and hepatitis B,” he says.
“And the common cold?” I ask.
He nods yes, adding that they’ve already recoded bacteria to be virus-resistant. “It’s in a paper we published in 2016,” he says.
Church and others who are working to synthesize human DNA have created their own effort within GP-Write—the Human Genome Project-Write, or HGP-Write—and its prospects for success have biologists abuzz over the potential for treating diseases and for creating bioengineered cells and possibly even organs. Critics, though, are scratching their heads over the technical challenges, high costs, and practicality. Francis Collins, director of the National Institutes of Health, acknowledges that synthesizing a full human genome is feasible, but he doesn’t quite see the point. “I think it’s probably within the range of possibility, given enough time and money,” he says, “but why would you want to do that? Technologies like Crispr are so much more accessible right now.”
There are also the ethics of using a powerful new technology to muck around with life’s basic coding. Theoretically, scientists could one day manufacture genomes, human or otherwise, almost as easily as writing code on a computer, transforming digital DNA on someone’s laptop into living cells of, say, Homo sapiens. Mindful of the controversy, Church and his HGP-Write colleagues insist that minting people is not their goal, though the sheer audacity of making genome-scale changes to human DNA is enough to cause controversy. “People get upset if you put a gene from another species into something you eat,” says Stanford bioethicist and legal scholar Henry Greely. “Now we’re talking about a thorough rewriting of life? Hairs will stand on end. Hackles will be raised.”
Raised hackles or not, Church and his team are forging ahead. “We want to start with a human Y,” he says, referring to the male sex chromosome, which he explains has the fewest genes of a person’s 23 chromosomes and is thus easier to build. And he doesn’t want to synthesize just any Y chromosome. He and his team want to use the Y chromosome sequence from an actual person’s genome: mine.
“Can you do that?” I stammer.
“Of course we can—with your permission,” he says, reminding me that it would be easy to tap into my genome, since it was stored digitally in his lab’s computers as part of an effort he launched in 2005 called the Personal Genome Project. (Disclosure: I’ve reported on Church for more than a decade, and he serves as one of 17 unpaid advisers to a small conference series I run called Arc Fusion.) The PGP has enlisted thousands of individuals to contribute their complete genomes to a public database open to researchers and everyone else, and I had donated my genome to the effort.
With my permission and a few clicks on his keyboard, Church can easily pull up a digital blueprint of my Y chromosome. Then scientists in his lab could build a synthetic replica, only with a difference: They would recode my sequence to be resistant to viruses. And if they’re successful—and if they recoded the rest of my chromosomes and inserted them into a human cell, both huge ifs—they could theoretically implant these “corrected” cells inside my body, where they would hopefully multiply, change how my body functions, and lower my risk for viral infection.
But we’re getting ahead of ourselves. For now, Church merely wants to recode and synthesize my Y chromosome. “It’ll be a little bit of you,” he tells me, “that we’ll keep in a freezer once we’re finished.” An optimized version of me that could one day be thawed out, in a dozen or a hundred or a thousand years. By then, Church explains, scientists might be able to further manipulate my genome. They could make me stronger or faster or maybe even smarter. They could possibly build an entirely new version of me. Who knows what will be feasible in the future?
Synthetic biology, a field dedicated to understanding and reengineering the basic building blocks of life, has its roots in the early 1970s, when a team led by Stanford biochemist Paul Berg made key discoveries about how to cut and paste short DNA sequences from one organism (everything from bacteria to humans) into another (usually a bacterium). This practice allowed scientists to use a microbe’s cell machinery to crank out proteins that in some cases became blockbuster drugs like Epogen, now commonly used to boost red-blood-cell production for those with anemia or on dialysis—or, um, in the Tour de France.
Larger-scale synthetic biology began to take hold in the early 2000s, when scientists began to synthesize complete viruses. In 2010, a team at the J. Craig Venter Institute created the first synthetic, self-replicating bacterial cell. But nothing so far has approached the ambitions of GP-Write or HGP-Write, which take their names from the original Human Genome Project, the massive endeavor that sequenced the 3 billion pairs of letters making up a human genome at a cost of $2.7 billion to US taxpayers. (A second, private effort led by geneticist Craig Venter was completed for significantly less money.) “We are looking at HGP-Write as the bookend” to the Human Genome Project, says geneticist Andrew Hessel, one of the founders of GP-Write and HGP-Write and a former researcher in the life-science unit of software giant Autodesk.
It was Hessel, a lean 54-year-old with a short, prickly beard, who first told me about this new human genome project three years ago when I visited him in his small, funky cottage near the Russian River in California’s Sonoma County. Sipping red wine around a wood stove on a foggy night, Hessel talked about how he began his career in the late 1990s at Amgen analyzing data from Venter’s private human genome effort. “Even as we were finishing HGP-Read,” he says, using his and his colleagues’ shorthand for the original Human Genome Project, “I was looking forward to seeing how we could start making things. Then I waited and waited, but nothing happened. It was a failure of imagination. The technology had reached a certain point, but no one was moving on it.” He watched as Crispr and other gene-editing techniques emerged, but they didn’t satisfy him.