Church opens his lectures with his “conflict of interest” slide, a smorgasbord of company and university logos reflecting his incessant entrepreneurial and academic liaisons. Not every venture succeeds, but when they don’t it’s typically because Church’s ideas are too early—it takes times for everyone else to catch up. One of my favorites was a next-generation sequencing outfit in Silicon Valley called Halcyon that could read gene sequences by stretching a DNA molecule like a piece of bubble gum, allowing scientists to visualize the rungs of the double helix under an electron microscope.
He also founded Knome,I the first company to offer personal genome sequencing years before the $1,000 genome became a reality. The first customer, a Swiss biotech executive, paid a staggering $350,000 for the privilege. Other early clients included a member of the British royal family and Black Sabbath’s Ozzy Osbourne.2 One of his latest ventures, Nebula Genomics, aims to offer free genomes to customers using something he calls “sponsored sequencing.”3
He’s been a guest on the Stephen Colbert show discussing another futuristic line of research—using DNA as a computer to store reams of digital information. In 2012, Church’s team designed a bacterial genome with customized DNA sequence that encoded the full text of Regenesis. “Church has been accused of ‘playing God,’ an accusation abetted by his beard of biblical proportions,” Colbert joked in profiling Church for Time’s 100 most influential people.4 The comedian said Church “seems less like God and more like a cross between Darwin and Santa.”
Having spent three decades obsessing over the technology for reading DNA scripts, Church is increasingly fascinated by writing and editing DNA. He’s a leader in the synthetic biology movement and an organization called GP-Write (Genome Project-Write).II But it’s not just human genomes that Church is interested in customizing. Church was one of the early developers of CRISPR gene editing, briefly hosting Feng Zhang and publishing one of the first demonstrations of genome editing in human cells in January 2013. Church is always looking to go cheaper, better, faster. Genome editing is no exception. Church jokes that his middle initial (M) stands for “multiplexing.”
In Oryx and Crake, Margaret Atwood introduced us to the pigoon, a hybrid creature designed for the wealthy elite to supply “an assortment of foolproof human-tissue organs in a transgenic knockout pig host—organs that would transplant smoothly and avoid rejections.”5 Church believes he can revolutionize organ transplantation without going quite so far by providing a safe alternative source of compatible organs from genetically edited pigs. It’s been branded “weird science,” but if successful, Church’s company eGenesis could offer hope to the 115,000 Americans on the organ transplant waiting list.
While about one hundred transplants are performed daily in the United States, twenty patients die waiting for a suitable organ donor. “The closest thing we have to death panels in this country are the decisions made about who gets transplants,” Church says. Many people are rejected from an organ transplant because they have infectious diseases or drug addiction with the argument that they wouldn’t benefit from a transplant. “But of course they’d benefit. And if you had an abundance of organs, you could do it for everyone.”6
Church’s cofounder and chief technology officer at eGenesis is Luhan Yang, his former grad student and postdoc. Yang grew up in Sichuan Province near Mount Emei, one of the Four Sacred Buddhist Mountains in China—what she calls “Crouching Tiger, Hidden Dragon” territory. After excelling at Peking University, Yang moved to Boston in 2008, working with Prashant Mali on the Church lab’s proof of CRISPR gene editing in human cells. Church was soon contacted by physicians at Massachusetts General Hospital (MGH) about improving the prospects of xenotransplantation patients.
eGenesis is located not surprisingly in Kendall Square, one more ambitious biotech company among scores of cool start-ups and established biotech companies. Most aspire for the commercial success of their big pharma neighbors, including Novartis, Pfizer, Amgen, and Biogen. In the company’s reception, a flat-panel TV displays a montage of staff holiday photos in Cancun, a present from the company’s investors to celebrate the birth of the latest pig litter.
I’m greeted by Wenning Qin, a veteran pharma researcher who after spending most of her career knocking out genes in mice, jumped at the chance to apply her particular set of skills to pigs. Many aspects of the miniature pig’s biology make it an ideal organ donor substitute. Pigs have a short four-month gestation and large litters. Pig heart valves and corneas are already used in operations. But two major issues must be addressed before contemplating human transplant of kidneys, livers, and other organs. First, the pig genome contains dozens of embedded viral sequences (PERV, or porcine endogenous retrovirus). While these viruses don’t apparently cause any health issues in pigs, unchecked activity in humans could be very dangerous, especially in immunosuppressed organ recipients.
In 2017, eGenesis used CRISPR to successfully remove all sixty-two PERV sequences in the DNA of a pig cell line. The record-setting multiplexing feat made the cover of Science under the tasty headline “CRISPR Pigs.”7 Yang’s team named the first CRISPR pig Laika, in honor of the stray Soviet dog that became the first live animal in space.8 Since then, Qin’s team has generated a separate line of PERV-free miniature pigs in the United States, named after Greek goddesses: Iris, Hestia, Maia, and Nike, the goddess of victory. Dozens of additional gene edits will be required before clinical trials can commence. The goal is to eliminate, or at least minimize, the risk of immune rejection of a transplanted pig organ. One target gene, for example, codes for an enzyme that produces sugar molecules on the cell surfaces of pigs and other mammals, but not humans.
The precious pig cells are kept frozen in a large liquid nitrogen tank. Any power failure would trigger multiple alarms on staff phones including Qin’s. “Would you like to see some pig cells?” she asks. Before I can answer, she lifts a plastic dish containing ninety-six wells out of an incubator and slides it under a microscope. These CRISPRed cells could one day provide a production line of life-saving organs. On a nearby farm, the first piglets with edited immune genes are already trotting around, named after characters in The Adventures of Tom Sawyer and The Last of the Mohicans.
Back in Boston, pig organs are currently being transplanted into monkeys in preclinical experiments being led by James Markmann, chief of transplant surgery at MGH. Meanwhile, in Hangzhou, China, Yang has taken on a new role as CEO of eGenesis’s sister company, Qihan Biotech. Qin tells me the name means “through learning you come to understand” and “a flower ready to blossom.”
But it’s Church’s work on another mammal that has truly captured the attention of the media (and Hollywood): the woolly mammoth, Mammuthus primigenius, the flagship project of the de-extinction revolution. Woolly’s backers include venture capitalist Peter Thiel, on a mission to defeat mortality, who donated $100,000 early on in 2015.
The story begins, and may yet resume, in Siberia—about five million square miles of permafrost. Entombed within this deep-soil layer are the remains of animals and plants, a refrigerated repository of an estimated 1,400 gigatons of carbon. If this is released as methane, as global temperatures rise, the compounding effect on the climate would be devastating. The solution proposed by father-and-son team Sergey and Nikita Zimov isn’t exactly Jurassic Park but a 4,000-acre pilot project dubbed Pleistocene Park. They plan to restore the ancient ecosystem with mammoths and other animals trampling the insulating snow to enable the arctic frost to penetrate the soil, in turn chilling and compressing the yedoma layers deeper into the ground, postponing thawing and methane release. That’s the theory, anyway.