Scientist proposes genetic attack on Martha’s Vineyard ticks

In battling Lyme disease, MIT associate professor Kevin Esvelt seeks to create a new paradigm in scientific research.

MIT professor Kevin Esvelt in his lab. — MIT Media Lab

Massachusetts Institute of Technology associate professor Kevin Esvelt came to Martha’s Vineyard on Wednesday to make separate presentations to Island health agents, and to the public, to enlist support in a potentially groundbreaking tactic that could vastly reduce the cases of Lyme disease on the Island, and possibly far beyond our shores.

“Our proposal is to permanently break the transmission cycle between white-footed mice, which are the reservoir of most diseases, and ticks,” he said at a monthly working session of health agents at Oak Bluffs town hall.

For the most part, the Island health agents seemed receptive, and asked numerous questions.

Ticks are not born with the Borrelia burgdorferi bacterium that causes Lyme disease. They most often acquire it during their first blood meal when they feed on white-footed mice, the major reservoir for the bacterium.

“If we reduce the number of infected ticks, then we can reduce the number of Lyme disease cases. We can now conceive of making mice that are resistant to the Lyme bacteria,” he said.

Mr. Esvelt proposes that by making Lyme-resistant mice in the laboratory and gradually introducing them into the wild, the immunity will spread through the mouse population, and the reservoir of Borrelia burgdorferi would eventually collapse.

To achieve this, white-footed mice would be vaccinated with OspA, the same protein as in LYMERix, which is used in the current dog vaccine and was used on humans for four years until it was pulled from the market in 2002 in reaction to lawsuits. Immune cells from vaccinated mice with the strongest resistance will serve as a source of genes encoding the antibody response; those genes will then be inserted into the mouse genome. The most disease-resistant would be bred on a large scale and released periodically into the wild, where the immunity genes would spread into the mouse population.

Sam R. Telford III, professor at the Cummings School of Veterinary Medicine at Tufts University, is the ecologist for the project. He has been studying ticks and tick-borne diseases on the Vineyard for 20 years and on Nantucket for 30 years. He currently has a small number of vaccinated mice in his laboratory. “Their ancestors came from Felix Neck in 1994,” he told The Times. “The National Institutes of Health has been funding their propagation. They’re expensive mice.”

This is not to say genetically fortified mice will be scurrying around the Vineyard anytime soon. Wednesday’s presentations were the first step in a long journey that will take about a decade before the arrival of genetically altered mice is even a possibility.

According to Mr. Esvelt’s timeline, if all goes well, mice breeding will be done by 2020, after which they will be introduced to an uninhabited island, perhaps Tuckernuck, and then studied for two more years.

“You can study all you want; we just don’t know until you put them out in the wild, which is why an uninhabited island is ideal,” Mr. Esvelt said.

Besides a close monitoring of the tick and mouse population, owls and possibly other predators will be tagged and studied for any ecological red flags.

If that stage of the study goes well, the Lyme-resistant mice would be introduced on Nantucket and Martha’s Vineyard around 2023.

The number of mice to be released is based on 10 percent of the local population, four to five times a year. “On the Vineyard, that’s a hundred thousand or more,” Mr. Esvelt said.

The same presentation was made to Nantucketers in early June. Board of health chairman Dr. Malcolm MacNab told The Times that the presentation was well-received. “There were a few people I thought would object, but were receptive to the idea,” he said. “I think the feeling is, let’s get going and see how it goes. We have to do everything we can.”

Research reboot

While the science behind Mr. Esvelt’s experiment has groundbreaking implications, his methodology could turn scientific research on its head.

“This project is only a concept, and can only move forward if the community embraces it,” he said. “We’re interested in demonstrating a new form of community-responsive science to make a fundamental change in the way science progress is made. We want the public involved from the start, in this case, so people do not run for the hills when they hear ‘genetically altered’ and ‘rate of Lyme disease infection.’ Rather than working secretly in laboratories across the world and springing discoveries on the world, we want to show that science should be done in the open. When scientists work behind closed doors, they can unnecessarily duplicate work. Science will advance faster and safer if we share earlier. Everybody benefits.”

The basic tenets of how the community-driven experiment should work, if the Vineyard or Nantucket elected to participate, were hatched at a workshop at MIT last December. Attendees included scientists, ethicists, Vineyard and Nantucket residents, nongovernmental organizations, and state and federal regulators.

Today’s presentations, “showing the clear benefits to citizens,” was step one.

“This can only move forward if it’s embraced by the community. Discussions need to take place before the work is begun. I want to hear from the people who think this should never be done. We want all points of view,” Mr. Esvelt said. “Keep in mind there will be built-in stopping points to be voted on along the way, where the community can scrap the whole thing.”

It was also decided that an independent organization will monitor the work and analyze the results.

“It has to be run by nonprofit groups, that’s essential,” he said. “If someone is making a profit, you are going to be suspicious.”

Governmental agencies — Massachusetts Fish and Wildlife, Environmental Protection Agency (EPA), and, because it involves the genetic altering of a mouse, the Food and Drug Administration (FDA) — will all have their say as well. “Traditionally, the agencies approve it before the public knows anything about it, and can’t do anything to change it. That’s not how we will work,” Mr. Esvelt said.

Speaking to The Times before the afternoon presentation at Edgartown library, Mr. Esvelt explained that the experiment was not inspired by Lyme disease per se. “There wasn’t a single aha moment about Lyme disease,” he said. “I was thinking about what would be the ideal place to solve a shared problem with community-driven science. It seemed that Lyme disease here and on Nantucket, and [dengue-transmitting] mosquitoes on Hawaii would be the best places to approach this. Lyme disease is much more widespread. And mice are easier to work with than mosquitoes.”

Mr. Esvelt said the work he hopes to begin here could benefit people worldwide. “Communities on the Island have an opportunity to pioneer this,” he said. “If we’re successful here, we could consider spreading if we show that open and responsive science works. This has implications for malaria and schistosomiasis, also known as snail fever.”

Earlier in the day, Mr. Esvelt said there is also a personal stake in his work. “I live in Newton. I have a 3-year-old son. My wife is a pediatrician, and she sees Lyme disease all the time,” he said. “We have woods that border our property. My son used to play in the woods, and that’s really the iconic image of American childhood. But now he can’t do that. I think that’s pretty bad,” he said.

“I’m just as interested in how we decide whether, when, and how to alter our shared environment,” he said. “I think the best way to do that is to start at the small scale, take a local grassroots approach, see if it works, and if things go well and you have local support on a very small scale, then you can talk about scope. That means this project could become a model for how we make decisions in communities all over the world.”