7/12/2017

Can these scientists bring back the mammoth? - The Boston Globe

Can these scientists bring back the mammoth?

Ben Mezrich’s wild and woolly tale of how and why a team of Harvard researchers are working to return a signature species from extinction.

By Ben Mezrich   June 16, 2017

EARLY FALL 2008, BOSTON https://www.bostonglobe.com/magazine/2017/06/16/can-these-scientists-bring-back-mammoth/NVAt4Hap0BsfrNqwpziM5N/story.html

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Can these scientists bring back the mammoth? - The Boston Globe

Sometimes, it’s the strange questions that keep you up at night. George Church leaned back in his chair, his long legs tucked beneath the desk in the middle of his stark, brightly lit office nestled deep in a corner of his second-floor laboratory at the Harvard Medical School New Research Building. His right hand was still resting on the phone in front of him, long after he’d hung up, his feet bouncing against the carpet beneath the desk in the selftaught routine he used, as a narcoleptic, to keep himself awake. He wasn’t sure how long he had been sitting there, staring at the phone, after having spoken to a journalist who had posed an astonishing question. He could tell by the dark sliver stretching across the bottom of the drawn window shades on the other side of the 10-by-10 space that the afternoon had shifted to early evening. Nor would it have helped to open the door behind him and peer out into his lab. The young scientists — best guess, now numbering in the seventies — who called the Church Lab[1] home made their own schedules. And most of them had little use for watches, clocks, daylight, really — anything beyond the cinder-block walls of the building. At midnight on any Wednesday, there might be 25 postdocs huddled around the various sterile plexiglass hoods lining the twists and turns that separated Church’s office from the pair of elevators leading down. Church rose from his desk and turned toward the bookshelf that lined most of the back wall of his office. It took him a few minutes to find the handful of zoology textbooks he’d kept from his college years back at Duke. He retrieved a couple of the more basic tomes and spread them out by the telephone, open to equivalent sections, on a specific species of animal. Get Today's Headlines in your inbox: The day's top stories delivered every morning. He sat back down, leafing through various photos in the textbook while reviewing the phone conversation again in his head. It wasn’t every day that a journalist called to ask Church to discuss performing a miracle — though it wasn’t as rare as one might think. Church had helped originate the Human Genome Project; develop much faster and less expensive technology to sequence genomes; produce synthetic forms of biology for tailoring simple life forms like bacteria (programming them to glow like Christmas lights, feed on waste, or even act as biological fuel); and start a Personal Genome Project that could yield personalized medicine. He’d authored hundreds of groundbreaking papers, and he had been awarded more than 60 patents. He’d cofounded more than a dozen companies and changed the practice of both genetic sequencing and genetic engineering. And that wasn’t counting the work of the brilliant young scientists he had gathered at the Church Lab. https://www.bostonglobe.com/magazine/2017/06/16/can-these-scientists-bring-back-mammoth/NVAt4Hap0BsfrNqwpziM5N/story.html

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Can these scientists bring back the mammoth? - The Boston Globe

So he hadn’t been surprised to hear from Nicholas Wade, a well-known science writer from The New York Times, but he was surprised that Wade hadn’t called to discuss Church’s projects. Wade had called to talk about the woolly mammoth. Wade was working on an article about a team of scientists at Penn State who were about to publish a paper announcing an effort to decode the genetic material of one of the prehistoric creatures, culled from a hair sample they had retrieved from somewhere in the Arctic Circle. The scientists at Penn State believed that for around $2 million, they could sequence the mammoth. Church was not an expert, but as a zoology major and a fan of conservation in general, he knew a bit about the woolly mammoth. The iconic creature had mostly died out around 10,000 years ago, succumbing to some extent to changing environmental conditions at the end of the last ice age, and hunted to extinction by prehistoric humans. More than 16 feet high at the shoulders and weighing more than 20 tons, some of them were covered in long reddish hair. Despite the most common images in popular culture, woolly mammoths came in a variety of colors, similar to the variations found in human hair. And mammoths, unlike their future elephant relatives, had evolved a special hemoglobin that could function in cells very close to the freezing point for indefinite lengths of time. Their short ears and tails resisted frostbite, and they had been supremely well adapted to the cold environments of the Arctic and the northern steppes of Siberia and North America. “Let’s say they’re successful,” Wade said. “Let’s say they sequence the frozen material. Would it then be possible, using genomic engineering, to resurrect a woolly mammoth?” Like many other people, Church had read Michael Crichton’s novel Jurassic Park and seen the movie based on it. Unlike most people, he knew that Jurassic Park was pure science fiction. Cloning dinosaurs from genetic material harvested from a prehistoric mosquito caught in amber was impossible for many reasons. Dinosaurs had died out 65 million years ago, which meant there was no such thing as extant dinosaur DNA to be found in our modern era. No genetic material could survive even a fraction of that length of time. It would have been continuously bombarded by cosmic radiation or consumed by enzymes in the soil, which would destroy the DNA. There was nothing at all to sequence.

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Can these scientists bring back the mammoth? - The Boston Globe

Reprinted by permission of Atria Books, a division of Simon & Schuster Inc. But the woolly mammoth was different. Woolly mammoths were now being pulled from the Arctic ice in remarkably pristine condition, essentially flash frozen at the time of their deaths. And unlike dinosaurs, some of these mammoths might be merely a few thousand years old. Still, despite the near-perfect appearances of some frozen specimens, attempts at growing live cells from the long-dead beasts had so far ended in failure. The DNA had deteriorated over the centuries beneath the ice. In spite of imaginative fiction, scientists were not likely to be regrowing extinct creatures in a lab any time soon.

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Can these scientists bring back the mammoth? - The Boston Globe

But Church wondered, what if you didn’t need to regrow a mammoth from a deteriorating, frozen sample? What if, instead, you approached de-extinction the same way his lab was approaching his other genetic engineering projects — with rapidly sequenced genomes and synthetic modifications to cure disease or create new bacteria? What if you could take the code for what made a woolly mammoth a woolly mammoth and implant it into one of the mammoth’s modern relatives? Church looked down at the pages of the zoology books he’d spread across his desk. A half-dozen pictures of elephants stared back at him from their jungle and savanna habitats in Africa and Asia. On the surface, they seemed far removed from their giant red furry cold-weather ancestors, which had once roamed the Siberian tundra. But were they really so far apart? Church hadn’t meant to give Wade’s question a definitive answer. He always tried to be careful with journalists and to frame his answers with enough caveats to cover himself. Good journalists weren’t trying to be provocative, they were simply asking what was possible, what couldn’t be ruled out. But in answering Wade’s question about whether it could be possible to use genomic engineering on a sequenced woolly mammoth genome, Church had replied, “It’s certainly possible.” Now, hours later, he was looking at pictures of elephants, his mind deep into what was still a theoretical game. His wife and daughter, having finished dinner, were likely heading to bed. Well, actually, his wife, Ting, being an insomniac, would surely be awake and ready to talk . . . about anything. Maybe their conversation would lead to a paper in a scientific journal, maybe it would become a thought exercise to get the hearts of the postdocs on the other side of the office door thumping. But Church was already spooling ahead. With the sequence to the woolly mammoth genome, Church believed he could synthesize and implant the proper DNA code into an elephant embryo and essentially allow a modern elephant to give birth to its own ancient ancestor. You couldn’t bring a woolly mammoth back to life, but you could essentially create one. All you needed was that genetic code and a proper flesh-and-blood incubator. A FEW DAYS AFTER HIS PHONE CALL with Nicholas Wade, Church received an odd little e-mail from Stewart Brand. Most people know Brand as the revolutionary thinker who founded the Whole Earth Catalog[2] or as the person known for the phrase “Information wants to be free.” Church knew him more as the husband of Ryan Phelan. Her 1995 startup Direct Medical Knowledge had become the backbone of what was now known as WebMD, and 10 years later, Phelan had founded a company called DNA Direct, offering genetic testing to customers via the https://www.bostonglobe.com/magazine/2017/06/16/can-these-scientists-bring-back-mammoth/NVAt4Hap0BsfrNqwpziM5N/story.html

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Can these scientists bring back the mammoth? - The Boston Globe

Internet. By screening for preconditions for more than a half-dozen diseases, DNA Direct had been aimed at the same sort of personalized medicine that Church foresaw for his Personal Genome Project. Brand had reached out to see about cloning an extinct animal. Not a woolly mammoth, but a passenger pigeon, once the most abundant bird on the planet. For conservationists and long-term thinkers such as Brand and Phelan, extinctions represent a devastating threat to the planet. As a technologist, Brand had begun to wonder, was there a way to use the passenger pigeon as a model for reversing the dangerous trend? Church, already on overdrive contemplating the de-extinction of the mammoth, had responded to the e-mail with optimism and with detailed thoughts about how they might bring back the extinct bird. It was more than Brand and Phelan had expected. Inspired, they had traveled to Boston, arranging a face-to-face meeting with Church at a cafe near his lab. As Brand remembers it, Church walked in and introduced himself with a simple statement: “I’m George. I read and write DNA.” There he was, this incredibly tall man with an immense beard and wild hair, describing himself in five words. Phelan and Brand became instant fans. Clearly, science was rapidly moving from passive observation to active creation, and this was the man who was helping make that happen. Church shifted their conversation away from the passenger pigeon to the woolly mammoth. Both were keystone species that had once been plentiful, and both had been hunted to extinction. But the woolly mammoth, to Church, was more compelling. Maybe it was the state fairs and circuses he had attended in Tampa, Florida, as a kid, where he’d marveled at the enormous elephants, so gentle and intelligent. Ethically, both species deserved a second chance. But to Church, there needed to be more than an ethical reason to embark on such a complex project. Church wasn’t a conservationist or a philosopher. He was a chemist/geneticist, and if he was going to take a shot at a miracle, he needed a real motivation, something that would inspire a team of postdocs to take time away from whatever had brought them to his lab in Boston in the first place. He believed it was scientifically possible to bring back a woolly mammoth. But why would you want to? Why would you need to?

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Can these scientists bring back the mammoth? - The Boston Globe

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OCTOBER 2012, WASHINGTON, D.C. Church, hoping to find a reason to bring back the mammoth, had come  to Hubbard Hall, the original home of The National Geographic Society, for a conference on de-extinction organized by Brand and Phelan. He was most excited by the presentation of Russia’s Sergey Zimov, who detailed how the warming of the permafrost, the inhospitable 10- to 11-foot-thick crusts of tundra in much of the world’s northernmost climes, actually presented a greater danger to the earth’s climate than the melting of the ice caps. Zimov outlined his decades-long effort to slow the warming of Siberia’s permafrost by recreating prehistoric, pre-human conditions. The tundra had once been vast grasslands teeming with massive herbivores, including mammoths, all continually trampling and turning the topsoil as they grazed. As they naturally tilled the earth, they churned the soil to expose the https://www.bostonglobe.com/magazine/2017/06/16/can-these-scientists-bring-back-mammoth/NVAt4Hap0BsfrNqwpziM5N/story.html

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Can these scientists bring back the mammoth? - The Boston Globe

frozen ground beneath to the even colder air, keeping the permafrost perpetually chilled. By reintroducing small herds of elk, bison, and other herbivores, as well as using a decommissioned military tank to simulate the weight of a mammoth, he’d re-created ancient grasslands in a small area of Siberia, and thus lowered the temperature of its permafrost by 15 degrees. But to make a difference on a large scale, he needed a herd of mammoths. The rest of the scientists listening to his presentation had laughed, while Church exchanged looks with Brand and Phelan. The Russian scientist had just given them their reason to resurrect their species. That conference was the beginning of the Woolly Mammoth Revivalists[3], the team Church, Brand, and Phelan would create to pursue their quest. Over the next five years, Church’s lab succeeded in engineering 14 parts of the mammoth genome, including those responsible for its hemoglobin process and that create the mammoth’s namesake coat. Still, we are likely decades away from the actual return to the wild of mammoths, says Brand. But it could be merely a few years before mammoth genes are spliced into modern Asian elephants to create an elephantmammoth hybrid that could help preserve the permafrost. This work might also lead to the de-extinction of more recent, faster-reproducing species like the passenger pigeon. It could prevent the disappearance of some critically endangered species by helping to expand their gene pools. Finally, all this work with elephant genes might help us discover whether there’s a genetic reason elephants rarely get cancer. Finding genetic code that stifles cancer would, of course, be even bigger than bringing back a woolly mammoth. Ben Mezrich [4]is a Boston-based author whose 18 books include New York Times bestsellers “The Accidental Billionaires” and “Bringing Down the House.” From “Woolly: The True Story of the Quest to Revive One of History’s Most Iconic Extinct Creatures[5]” by Ben Mezrich. Copyright © 2017 by Ben Mezrich. Reprinted by permission of Atria Books, a division of Simon & Schuster Inc. Send comments to [email protected][6].

Links 1. http://arep.med.harvard.edu/gmc/ 2. http://www.wholeearth.com/issue/1010/ 3. http://reviverestore.org/projects/woolly-mammoth/woolly-mammoth-revivalists/ 4. http://www.benmezrich.com/ 5. http://www.benmezrich.com/books/woolly/ https://www.bostonglobe.com/magazine/2017/06/16/can-these-scientists-bring-back-mammoth/NVAt4Hap0BsfrNqwpziM5N/story.html

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Can these scientists bring back the mammoth? - The Boston Globe

6. mailto:[email protected]

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