DNA Wars in Cambridge

Three Cambridge biotech startups are vying for control of a revolutionary gene-editing tool called CRISPR-Cas9. On the line are a billion-dollar market, a potential Nobel Prize, and, yes, the power to resurrect an extinct species.

If reproductive gene editing doesn’t scare you, try this: A real-life Jurassic Park is being cooked up right here in Boston. George Church believes that editing animal genes will benefit humanity far more than editing human genes. So mammoths, mosquitoes, and pigs are the most important CRISPR subjects in his lab. In fact, gene therapy for people is Church’s fourth and last priority, because genetic counseling already helps most individuals with genetic disorders who want to become parents. He sees more potential in harvesting pig organs for human transplants, editing malaria out of mosquitoes, and—yes—curbing climate change with woolly mammoths.

While Editas races to find gene-editing therapies for humans, another company Church cofounded, called eGenesis, is working on ways to make pigs’ organs safe to transplant into humans. “Essentially, every organ that is transplanted could also be harvested from pigs,” he says. “They’re about the right size and shape.”

Since the 1990s, scientists have explored whether cross-species transplantation could someday relieve organ shortages in people. The problem is that pigs’ DNA is infected with viruses that could be transferred to humans. This past October, Church announced a breakthrough that could lead to a solution: His lab used the CRISPR technique to edit and disable 62 viruses in pig embryos. EGenesis plans to implant the embryos into mother pigs at Harvard Medical School and raise them to adulthood, isolated from disease. Church hopes his discovery could eventually help end many transplant shortages for humans. “There’s a million people that could use a transplant,” he says, if not for the “long, interminable queue.”

Church also thinks CRISPR could halt the spread of malaria, saving the lives of more than 600,000 people a year. “For malaria, the vaccines and drugs haven’t shown promise of being permanent solutions,” he says. So in 2014, he cowrote a paper proposing the use of CRISPR to change the genes of certain mosquito species, shutting off their ability to carry malaria and suppressing the size of their population. Researchers first proposed fighting malaria with mosquito genes in 2003, but progress was slow until CRISPR came along.

Even in the case of genetically modified mosquitoes, the CRISPR technology sets off all sorts of alarm bells about the dangers of altering nature. While thousands of mosquito species exist, only a handful of them spread malaria—so who cares if we exterminate the ones infecting more than a million people each year? Turns out, there may be a dark side to it: Eliminating one type of mosquito could mess with the food chain, or stop the pollination of a certain flower. “We might want to do more homework on the ecosystem role of each of these species,” Church says with great understatement. “It would merit additional funds for ecologists who specialize in pollination and mosquito-eating animals to weigh in on this seriously. There’s plenty of time.”

With this in mind, Church has started his work on malaria slowly, experimenting with yeast cells instead of going straight to mosquitoes. “Before we did it,” Church says, “we talked about a cautionary note, and what the solutions might be: how to do it more safely in the lab, how to do it more safely in the wild, how to reverse it if somebody does it incorrectly.” Church and his collaborators wrote a layman’s version of their research paper’s big questions for Scientific American.

Since he began in 2014, Church has found success in yeast, so now he has a graduate assistant experimenting with the mosquito responsible for nearly all malaria transmission to humans in sub-Saharan Africa. He thinks gene-edited mosquitoes could be released in Africa in as few as five years.

As for his mission to bring back the woolly mammoth, Church reached a breakthrough by creating a hybrid creature: part mammoth, part Asian elephant. Thanks to frozen mammoth bodies found in the far-northern permafrost, scientists have already mapped a lot of the animal’s DNA. Last year, Church announced that his team has used CRISPR to splice 15 mammoth genes into the DNA of Asian elephants: genetic codes for hair, smaller ears, a thicker layer of fat, and hemoglobin that can deliver oxygen to cells at a colder temperature. “We’ve got some promising-looking elephant embryos,” Church crows.

CRISPR makes it easy to create elephant-mammoth hybrids in a test tube, but Church still has a long way to go before his herds of woolly pachyderms are stampeding across Siberia. The hard part—the engineering and ethics challenges—will be bringing the newly conceived creatures all the way to birth and adulthood. Theoretically, biologists could just implant the elephant-mammoth embryos into female Asian elephants and see how the elephant mothers react when they birth babies with mammoth hair. But Asian elephants have enough problems already. “They’re an endangered species,” Church says. “We don’t want to interfere with their reproduction.”

Instead, Church and his lab team are going to raise their elephant-mammoths the hard way, similar to eccentric millionaire John Hammond’s technique in Jurassic Park: They hope to be the first to artificially incubate a mammal all the way from conception to birth. It sounds like pod-creature sci-fi, but Church seems fairly optimistic. Researchers have gotten mouse embryos to grow pretty big in a lab, he notes, while human medicine is getting better at caring for severely premature infants. If incubation technology can meet in the middle, Church says, they’ll be ready to tackle the next challenge: “the proper physiology, feeding, and education of the babies, if you’re going to create a whole herd.”

For Church, it’s not just the novelty of reviving an extinct species—though he acknowledges the mammoth’s strong pull on the public’s imagination. “They’re gigantic, they’re charismatic, and they’re not carnivores,” he says, “so we don’t immediately face the Jurassic Park scenario.” Church says the mammoth-elephant project is also an especially exotic example of ecosystem conservation: saving a key endangered species whose habitat is threatened by overlap with humans. Also, Church notes, humans likely hunted the woolly mammoth and may have helped to drive it to extinction. Reviving its DNA could be the ultimate amends for the damage our ancestors caused.

Between gene editing in animals and gene therapy for humans, Church thinks CRISPR could save millions of people’s lives in the next decade. “I know a lot of the reason my generation went into science was because of JFK’s moon project,” he says. “It was something that inspired us. I think this generation should be even more inspired.”

As for the patent war, Church isn’t concerned that it will get in the way of Editas’ prospects, or its competitors’. “Usually, the reason you enforce patents is because two companies are doing the same thing,” he says. “There are a lot of diseases to cure, and I think [the companies are] doing different things.” After all, a small detail like patent licensing can always be worked out later—especially among neighbors.