OF MICE & MEN

Written By: Robert Cocuzzo | Photography By: Kit Noble

Meet the scientist who wants to fight Lyme disease on Nantucket with genetically modified mice.

By the time Dr. Kevin Esvelt left the Nantucket Board of Health’s special meeting last June, news of his visit was already spreading across the country. The New York Times, The Boston Globe, The New Yorker, and many other newspapers and magazines from Martha’s Vineyard to New Mexico quickly ran articles about this MIT scientist’s radical proposal to eradicate Lyme disease and other tick-borne illnesses on Nantucket.

Esvelt’s proposal sounded straight out of a Michael Crichton novel. To break the circle of infection, he proposed releasing fifty thousand genetically modified mice on the island that would not only be hyper-immune to tick-borne illnesses, but might actually cure infected ticks that bite them. If all went according to plan, he said, the prevalence of Lyme disease on the island could go down by 90 percent. The model might then be scaled up to tackle the problem on the mainland and beyond.

“The world is pretty magical,” Esvelt says, nodding out the window of his office at MIT, now eight months since that meeting on Nantucket. “You just need to learn how it really works in order to change it.” Esvelt is an evolutionary biologist advancing the science that Darwin embarked upon nearly two hundred years ago. Appropriately enough, his obsession with evolution began where it began for Darwin himself.

When he was just eleven years old, Esvelt’s parents took him on a trip to the Galapagos Islands. “That sort of crystallized it in my mind,” he says. “There isn’t such a thing as magic, but science is a pretty good proxy.” Esvelt went on to graduate magna cum laude from Harvey Mudd College. He earned a PhD in biochemistry from Harvard University and then a fellowship at Harvard. Now as an assistant professor at the MIT Media Lab, Esvelt is a pioneer in evolutionary biology who might have just found his own Galapagos with Nantucket.

In what he calls “sculpting evolution,” Esvelt and his team are developing highly sophisticated tools and methods to edit genes in organisms that can then dramatically impact the natural world. While other scientists are leveraging this technology to fight malaria and dengue fever by genetically re-engineering the mosquitoes that carry those afflictions, Esvelt is out to defeat Lyme disease — but not by targeting ticks.

The white-footed mouse is the primary reservoir for Lyme disease and tick-borne illnesses on Nantucket. Esvelt believes that if he vaccinates a white-footed mouse against Lyme and then sequences its genome, he’ll be able to identify the antibodies that ward off the disease. He would then breed a colony of white-footed mice that are genetically engineered with those antibodies and release them on the island. As those genetically engineered mice mate with the wild white-footed mouse population on Nantucket, the powers of evolution will theoretically eliminate all instances of Lyme in their offspring and break the circle of infection.

The other option, which could be done separately or in tandem with the Lyme immunization, is to immunize the mice against ticks themselves. This might offer the added benefit of not only preventing Lyme disease, but also other tick-borne illnesses such babesiosis, anaplasmosis, and ehrlichiosis. This would also reduce the tick population overall.

“I have a really hard time thinking of something that could go wrong,” Esvelt says. “If anything, all the anticipated effects are restoring the system back to what it would be like if we hadn’t screwed it up with fragmented woodlands and lots and lots of deer… So we’re pushing everything back to the natural state.”

However, there are significant logistical and technical challenges to the project, which Esvelt “guestimates” would cost around $10 million for both Nantucket and Martha’s Vineyard. In order to raise 100,000 genetically modified mice, Esvelt and his team would first need an uninhabited test island. Another option is to raise the mice on a cargo freighter. Either way, he thinks it will take two and half years to raise enough mice for the project. Of course, before anything can begin, Nantucket must decide whether it wants to be the guinea pig for this unproven science.

“I want the community to be in the driver’s seat,” Esvelt says. “It’s the community’s project — it just has to be.” In a field typically defined by secrecy, Esvelt insists upon absolute transparency. He not only wants the community involved with the project, he wants skeptics to challenge his every step. “I want to make sure everyone raises every possible objection,” he says. “I hope people push us to be as rigorous and careful as we possibly can and require us to use the outside experts and safety monitoring.”

To ward off concerns of any corporate interests lurking behind the scenes, Esvelt says the project will have to be a nonprofit funded mostly by private donations. To meet these standards, a steering committee is being assembled that includes ethicists, doctors, scientists, community leaders and a skeptic charged with voicing the concerns of all the skeptics on the island.

“In my opinion that’s how science should be — as open as possible,” says the Nantucket Board of Health director Roberto Santamaria, who attended Esvelt’s presentation back in June. Santamaria believes Esvelt’s plan, while not perfect, is the most viable option for combating the island’s Lyme disease epidemic, which will reportedly impact a staggering 40 percent of the island’s population. “The biggest obstacle here is explaining to a nonscientific group a major, complex scientific process,” Santamaria says. “It’s getting people to understand that they’re not altering the environment itself, but rather amplifying something that is already present in the environment.”

Yet whether it’s tomatoes or white-footed mice, GMOs are a hot button issue. “Some people feel that evolution is evolution, and if we mess with the natural environment in any way we can create a butterfly effect,” Santamaria says. “Some people are adamantly against any genetic modification at any level and of any animal. And you can’t change their opinion hell or high water.”

Indeed, the very idea of genetically modified mice, let alone releasing tens of thousands of them, makes many people on Nantucket uneasy. “How is this going to effect the food chain and all the other creatures that are involved with the white-footed mouse?” asks Nantucket resident Danica Connors. “No matter how much they test for that in a lab — or even on an uninhabited island — we will not find all of the potential reactions of what can happen to that food chain.”

Connors is a “Lyme literate” herbalist who treats clients on the island, 90 percent of whom she says are fighting tick-borne illnesses. While she commends the transparency with which Esvelt is pursuing this project, Connors remains skeptical that the science can outmatch the powers of nature. “Even if we genetically modified another species, which I have enough ethics issues with, from what we have seen in the capacity of these spirochetes, it’s just a matter of time until they adapt past this genetic modification,” she says. “Nature’s time frame is so much different than humanity’s.”

This is not the first plan that’s been proposed to break the circle of infection on Nantucket. In 2005, Dr. Timothy Lepore, the island’s leading tick-borne disease expert, successfully petitioned the Board of Selectmen for an additional week of hunting to cull more deer on the island. “The town wanted to hang me in effigy after that,” Lepore laughs today. While the extra week of hunting succeeded in bagging an additional 250 deer, the public outcry it caused shot down the chance of it ever happening again.

“I think this is a very ingenious method,” Lepore says of Esvelt’s proposal. “I don’t think we’re disturbing the environment. I think it will reset in a certain period of time. It’s not something that we’re setting up that’s irreversible. And we’re using Nantucket mouse DNA, it’s not anything exotic. From my perspective, you can’t really come up with any great arguments against it.”

Nantucket is an extreme microcosm of a nationwide epidemic. According to a study by Johns Hopkins Bloomberg School of Public Health, between 240,000 and 440,000 Americans are infected with tick-borne illnesses each year, costing the US healthcare system upwards of $1.3 billion. If the project on the island proves successful, Nantucket might go down in the annals of medical history for helping cure one of mankind’s most persistent afflictions. “Nantucket has put itself on the world map many times before as a whaling community, as an abolitionist community, as a tourist community,” says Santamaria. “It would be great to be up there as a first in the scientific community as well.”

Back in his office at MIT, Dr. Kevin Esvlet waits as the gears of town government turn on Nantucket. From his perspective, this project represents more than just defeating tick-borne illnesses. If the community decides to pursue this project, it could serve as a model of how modern society and modern science worked together to achieve a common goal for the future of mankind.

“I personally believe that scientists should hold themselves morally responsible for all the consequences of their work, which means I’m on the hook for a number of things,” Esvelt says. “It’s very important to me that we figure out how to do this, and I think Nantucket is the best place to do that. It’s sort of a baby step, but it’s an important one that could be a model for how we do it for the future.”