Rewriting the Code of Life
We customize nature for our benefit: clearing forests, draining swamps, domesticating plants and animals and modifying them through breeding to better meet our needs or desires. But now we’re taking a more direct approach, as Michael Specter describes in the New Yorker:
Early on an unusually blustery day in June, Kevin Esvelt climbed aboard a ferry at Woods Hole, bound for Nantucket Island. Esvelt, an assistant professor of biological engineering at the Massachusetts Institute of Technology, was on his way to present to local health officials a plan for ridding the island of one of its most persistent problems: Lyme disease. He had been up for much of the night working on his slides, and the fatigue showed. He had misaligned the buttons on his gray pin-striped shirt, and the rings around his deep-blue eyes made him look like a sandy-haired raccoon.
Esvelt, who is thirty-four, directs the “sculpting evolution” group at M.I.T., where he and his colleagues are attempting to design molecular tools capable of fundamentally altering the natural world. If the residents of Nantucket agree, Esvelt intends to use those tools to rewrite the DNA of white-footed mice to make them immune to the bacteria that cause Lyme and other tick-borne diseases. He and his team would breed the mice in the laboratory and then, as an initial experiment, release them on an uninhabited island. If the number of infected ticks begins to plummet, he would seek permission to repeat the process on Nantucket and on nearby Martha’s Vineyard.
More than a quarter of Nantucket’s residents have been infected with Lyme, which has become one of the most rapidly spreading diseases in the United States. The illness is often accompanied by a red bull’s-eye rash, along with fever and chills. When the disease is caught early enough, it can be cured in most cases with a single course of antibiotics. For many people, though, pain and neurological symptoms can persist for years. In communities throughout the Northeast, the fear of ticks has changed the nature of summer itself—few parents these days would permit a child to run barefoot through the grass or wander blithely into the woods.
“What if we could wave our hands and make this problem go away?” Esvelt asked the two dozen officials and members of the public who had assembled at the island’s police station for his presentation. He explained that white-footed mice are the principal reservoir of Lyme disease, which they pass, through ticks, to humans. “This is an ecological problem,” Esvelt said. “And we want to enact an ecological solution so that we break the transmission cycle that keeps ticks in the environment infected with these pathogens.”
There is currently no approved Lyme vaccine for humans, but there is one for dogs, which also works on mice. Esvelt and his team would begin by vaccinating their mice and sequencing the DNA of the most protective antibodies. They would then implant the genes required to make those antibodies into the cells of mouse eggs. Those mice would be born immune to Lyme. Ultimately, if enough of them are released to mate with wild mice, the entire population would become resistant. Just as critically, the antibodies in the mice would kill the Lyme bacterium in any ticks that bite them. Without infected ticks, there would be no infected people. “Take out the mice,” Esvelt told me, “and the entire transmission cycle collapses.”
Esvelt has spoken about Lyme dozens of times in the past year, not just on Nantucket and Martha’s Vineyard but at forums around the world, from a synthetic-biology symposium in Chile to President Obama’s White House Frontiers Conference, in Pittsburgh. At every appearance, Esvelt tells the audience that he wants his two young children—he has a three-year-old son and a daughter who is almost one—to grow up in a Lyme-free world. But that’s not really why he speaks at infectious-disease meetings, entomology conventions, and international conservation workshops. He has embarked on a mission that he thinks is far more important.
Esvelt and his colleagues were the first to describe, in 2014, how the revolutionary gene-editing tool CRISPr could combine with a natural phenomenon known as a gene drive to alter the genetic destiny of a species. Gene drives work by overriding the traditional rules of Mendelian inheritance. Normally, the progeny of any sexually reproductive organism receives half its genome from each parent. But since the nineteen-forties biologists have been aware that some genetic elements are “selfish”: evolution has bestowed on them a better than fifty-per-cent chance of being inherited. That peculiarity makes it possible for certain characteristics to spread with unusual speed.
Until CRISPr came along, biologists lacked the tools to force specific genetic changes across an entire population. But the system, which is essentially a molecular scalpel, makes it possible to alter or delete any sequence in a genome of billions of nucleotides. By placing it in an organism’s DNA, scientists can insure that the new gene will copy itself in every successive generation. A mutation that blocked the parasite responsible for malaria, for instance, could be engineered into a mosquito and passed down every time the mosquito reproduced. Each future generation would have more offspring with the trait until, at some point, the entire species would have it.
There has never been a more powerful biological tool, or one with more potential to both improve the world and endanger it. Esvelt hopes to use the technology as a lever to pry open what he sees as the often secretive and needlessly duplicative process of scientific research. “The only way to conduct an experiment that could wipe an entire species from the Earth is with complete transparency,” he told me. “For both moral and practical reasons, gene drive is most likely to succeed if all the research is done openly. And if we can do it for gene drive we can do it for the rest of science.”
At the meeting on Nantucket, Esvelt assured residents that he and his team fully understood the implications of manipulating the basic elements of life. He said that he regards himself not just as a biologist but as the residents’ agent; if they stop showing interest in the research, he will stop the experiments. He also insists that he will work with absolute openness: every e-mail, grant application, data set, and meeting record will be available for anyone to see. Intellectual property is often the most coveted aspect of scientific research, and Esvelt’s would be posted on a Web site. And no experiment would be conducted unless it was approved in advance—not just by scientists but by the people it is most likely to affect. “By open, I mean all of it,” Esvelt said, to murmurs of approval. “If Monsanto”—which, fairly or not, has become a symbol of excessive corporate control of agricultural biotechnology—“did something one way,” he said, “we will do it the opposite way.”
There are fewer than a million white-footed mice on Nantucket, so a gene drive won’t even be necessary to insure the spread of Lyme-resistant genes. Esvelt plans to release enough genetically modified mice, tens of thousands of them, to overwhelm the wild population. (Since he could never house that many mice in his lab at M.I.T., he recently mentioned the idea of breeding them on a container ship.) That approach, however, would never work for Lyme on the mainland, where there are more than a billion white-footed mice scattered up and down the Eastern seaboard.
The battle against Lyme disease is just an early stage in an unprecedented effort to conquer some of mankind’s most pervasive afflictions, such as malaria and dengue fever. Despite a significant decline in deaths from these diseases over the past decade, they still threaten more than half the world’s population and, together, kill nearly three-quarters of a million people each year. Malaria alone kills a thousand children every day.
The Bill and Melinda Gates Foundation has invested tens of millions of dollars in the research of a team called Target Malaria led by Austin Burt, at Imperial College, in London. In laboratory tests, the group has already succeeded in using CRISPR to edit the genes of Anopheles gambiae mosquitoes, which carry the parasite that causes malaria, so as to prevent females from producing fertile eggs. . .
Later in the article:
For Esvelt, though, those achievements seem almost like secondary benefits. “For a lot of people, the goal is to eradicate malaria, and I am behind that a hundred per cent,” he said. “The agricultural people have the New World screwworm”—a particularly destructive pest also known as the blowfly—“they’d love to get rid of in South America. Everyone has a thing he really wants to do. And it makes sense. But I would submit that the single most important application of gene drive is not to eradicate malaria or schistosomiasis or Lyme or any other specific project. It is to change the way we do science.”
That is the message that Esvelt has been selling in his talks throughout the world, and the initial response, on Nantucket and Martha’s Vineyard—even from people who attended the meetings in order to object to the proposal—has been overwhelmingly positive. “I came here thinking I would say, ‘Absolutely not,’ ” Danica Connors, an herbalist and shamanic practitioner who opposes genetically modified products, said at the Nantucket meeting. “I am the first person to say that, tinker with Mother Nature, we are going to break it.” But she told Esvelt that she loved “the fact that you are a young scientist saying, ‘I want this to be a non-corporate thing and I want this to be about the people.’ ” Seeming to surprise even herself, she said, “You know, I want to see where you go with this. I am actually very excited.”
The article provides instances of perverse incentives in the way science is done today. For example:
Despite his awards, publications, and influential mentors, Esvelt struggled to find a job that would help him achieve his goals as a scientist and as a public educator. To many institutions, he seemed like a strange hybrid. He had certainly demonstrated great talent as a researcher, but he had also decided to become a sort of proselytizer. He long ago concluded that telling the story of science, and the choices it presents, is just as valuable as anything he might accomplish in a lab. Élite scientists often look down on that kind of advocacy and see it as sanctimonious. “Carl Sagan, to this day, has a reputation in the science community as someone who was obviously a great science communicator,” Esvelt said. “But people will say he wasn’t that important a scientist. That is insane. Look at his publication record. He was a fabulous scientist.”
Many universities were discouraging, in large part because they weren’t sure what to do with him. “Most places told me, ‘We are fine with you speaking out about open science, but not on our time,’ ” Esvelt said. This meant that, when it came to tenure decisions and professional evaluations, he would be judged solely on his work in the lab. “I just didn’t fit into any of their normal silos,” he said.
And he mentions others: the great secrecy with which scientists cloak their current research because of the competitive aspect of how the field is structured.