Mouse Trap

How genetically engineered, Lyme-fighting mice could be the future of public health

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As scientists battle bitter backlash over a plan to release genetically modified, Zika-killing mosquitoes in the Florida Keys, just 1,700 miles north a similar plan has caused much less of a fuss. On Martha’s Vineyard and in Nantucket, Kevin Esvelt, an evolutionary biologist at MIT, has proposed fighting Lyme disease using genetically engineered mice.

In the woody, coastal corridors of New England, tick-borne Lyme disease runs rampant. In the small Martha’s Vineyard town of Chilmark, for instance, Centers for Disease Control data has found more than 1,300 cases per 100,000 residents. In 2014, Massachusetts alone had 3,646 confirmed cases. Ticks often contract the disease from white-footed mice while still larvae, then pass it along to humans, deer and other mice when they bite. Create Lyme-immune mice, Esvelt proposes, and stop the spread of the disease.

In June, Esvelt appeared at a public meeting in Nantucket to present his idea. Last month, he attended a similar meeting on Martha’s Vineyard. In both places, reception to the plan was warm.

The idea is to use new gene editing techniques like CRISPR to engineer mice immune to either the pathogen that causes Lyme disease or a particular protein in the tick’s saliva. That way, when tick larvae munch on the mice, they won’t contract Lyme and spread the disease. If creating such mice is a success in the lab, as previous studies have suggested it could be, Esvelt would then seek permission to release thousands of them on a small, uninhabited island. And if after a few years the numbers of Lyme-infected ticks has dropped sufficiently, then at long last the mice might be released on Nantucket and Martha’s Vineyard.

“Tick-born disease is an ecological problem,” Esvelt told a meeting of the Nantucket Board of Health. “Our proposal is to enact an ecological solution, to break the transmission cycle that keeps ticks in the environment infected with these pathogens.”

But Esvelt’s project is as much a political experiment as it is a scientific one.

If the future of public health really is using genetically engineered mosquitoes and mice to stamp out disease, then, he believes, the scientific community needs to radically alter how it engages with the public.

It’s a constant struggle to get scientists interested in communicating,” Esvelt told me recently. “I think science does not have much of a future being done separate from public guidance. On their own, scientists can no longer anticipate the consequences of their work.”

Take the blowback against Zika-fighting mosquitoes. Recently, the Food and Drug Administration gave the green light to a proposal by British biotech firm Oxitec to release male mosquitos engineered to kill off the local mosquito population. The agency found the project’s potential Zika-busting benefits outweighed any potential for environmental impact. The project’s main obstacle now is the local population, some of whom feel Oxitec has distorted the facts of the project and kept the community in the dark.

In hopes of preventing such a scenario in New England, Esvelt has involved the local community in his Lyme-eradicating project from the start, even before his lab began hunting for Lyme immunity genes in mice. The main goal is to ensure that the community feels as though it is an active part of whatever scientific tinkering might impact the local ecosystem.

“We are considering deliberate alteration of the local environment,” Esvelt told the Nantucket health board. “And we should only ever consider that if it offers clear benefits.”

Esvelt is careful to frequently emphasize community control.

“This project is only a concept and can only move forward if embraced by the local community,” one of the slides in his presentation reads.

The experiment is designed to make it as easy as possible to swallow. Esvelt is a pioneer of a powerful technology called gene drive, which can be used to override natural gene selection to ensure that a desired trait is passed down throughout generations. But the Lyme-fighting mice he’s proposing don’t rely on a gene drive, or introducing any foreign DNA into the mice at all. He believes the introduction of foreign DNA, as with Oxitec’s mosquitoes, can be extremely effective but is also one of the main factors that makes the public squeamish about such projects.

In a community meeting, Esvelt tried to be upfront about the good and the bad. He referred to one of the studies the Lyme-immune mouse is based on as something he “more or less” believes and another as “sketchier.” And if the project were ever to be successful enough to move on to the mainland, he said, that would mean using a gene drive and non-mouse DNA, technology he admits many people view negatively.

Esvelt tends to reflect a view of science that is as skeptical as the public’s. Should the experiment proceed, he said, it would require different sets of people to monitor its success, in order to ensure safety and remove bias. The community should have veto power, as well as the power to dictate the terms. And, he said, it should be run by a non-profit organization, not a corporation.

“The way it’s done now, by time you’ve heard concerns and criticism, it’s too late to do anything about it,” he told me, “All you get is a thumbs up or thumbs down from the regulators, so you lose the opportunity to responsively redesign the technology at the beginning to make the project safer and more effective.”

Esvelt also believes local communities might have insights to add that could actually make the science better.

“People living in an environment know more about that environment,” he said.

Lyme disease is the most commonly reported vector-borne illness in the United States. Still, it is isolated primarily to the Northeast, Mid-Atlantic and upper Midwest. The 300,000 or so people that the CDC estimates it infects each year number nowhere near the millions that mosquito-borne diseases such as dengue fever affect.

Part of why Esvelt chose to focus on Lyme disease is where it occurs. It’s a problem that impacts well-to-do, educated, tight-knit communities—places where hundreds of people regularly turn up at town hall meetings to discuss issues like the local tick population. In Nantucket, Esvelt hopes to develop a model for how public science experiments might operate going forward.

“With Lyme disease, we have a remarkable opportunity to address a major public health problem while showing the world that informed local communities can and should guide the science from the beginning,” he told me. “The citizens of Nantucket and the Vineyard are in the driver’s seat. They’ll determine exactly how the mice should be altered, how that change should be tested for potential side-effects, and who should perform those tests. They’ll determine how to make the smallest possible change capable of addressing a shared ecological problem.”

Eventually, if it proceeds, Esvelt’s project will need approval from federal and state regulators, as well as the citizens of Nantucket and Martha’s Vineyard. Esvelt hopes they will be harsh—that they will push him to develop better, more rigorous science.

So far, though, Esvelt has not quite attracted the criticism he had hoped for.

At the Nantucket meeting, one citizen took the mic, identifying herself as an herbalist.

“I’m the first person to say if you go tinker with Mother Nature, we’re going to break it,’’ she said. “But you know what? Even I want to see where you go with this.’’

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