The West Coast has earthquakes and forest fires, the Midwest has tornados, and the South has hurricanes. “But here in the Northeast,” said Kevin Esvelt, an evolutionary biologist at the MIT Media Lab. “Lyme disease is our natural disaster.” More than 300,000 people in the United States are diagnosed with it each year.
Although humans catch Lyme disease after being bitten by black-legged ticks that feed on deer late in life, the path to infection begins when the ticks contract the bacterium Borrelia burgdorferi from feeding on infected wild white-footed mice. Now Esvelt, and his team of researchers from MIT and Cummings School, are using new CRISPR genome-editing technology to create white-footed mice immune to the bacterium. The mice will then be deployed as frontline soldiers in the war against Lyme on Nantucket and Martha’s Vineyard, the Massachusetts islands with some of the highest rates of Lyme disease in the country.
The project, dubbed Mice Against Ticks, wouldn’t exist if not for Cummings School Professor Sam Telford, an internationally recognized expert on tick-borne diseases, Esvelt said. “The only reason I thought this approach might be possible is that [Telford] collaborated with Linden Hu, a professor at Tufts School of Medicine, on developing a bait-based vaccine for white-footed mice—you put the bait out, the mice eat it, and they develop immunity.”
That work grew out of Telford’s early ’90s studies at the Harvard T.H. Chan School of Public Health identifying an antibody that makes mice resistant to Lyme, which ultimately led to the development of canine and human vaccines for Lyme. (The manufacturer took the human Lyme vaccine off the market due to controversy over now-disproven side effects.) At Tufts, Telford and Hu also have successfully vaccinated white-footed mice so that ticks that bite them fall off before they have a chance to ingest their full meal of blood.
Esvelt thought if his research team could clone the antibodies that make vaccinated mice Lyme resistant, they could use CRISPR technology to create and breed mice that are born already producing those protective molecules. “That’s not normally how the immune system works,” Esvelt said, explaining that acquired immunity from antibodies isn’t normally passed on to offspring. CRISPR will permit these scientists to encode antibodies from immune cells into mouse reproductive cells, so that immunity can be passed on to future generations of mice. Telford estimates that releasing the genetically altered white-footed mice could greatly reduce the transmission of Lyme disease on Martha’s Vineyard and Nantucket.
Telford has spent three decades trying to get these communities to implement Lyme-fighting measures, from promoting consistent use of insect repellants, to culling deer, to spraying insecticides onto the mice that carry Lyme. But progress in the battle has long been compromised, on the islands and elsewhere, by a lack of sustained public funding and interest. “HIV was just as new as Lyme disease when I started working on it in graduate school,” Telford said. “Now, although we’ve made great strides in preventing and treating HIV, we are seeing more Lyme disease infections in more places every year.” This new approach may finally offer a one-time, long-lasting intervention.
In a never-before-done approach to biotech, the researchers have proceeded with their research study in a manner comparable to civic governance. Beginning at public board of health meetings and community meetings during the summer of 2016, the team asked island residents if they wanted to genetically engineer mice to fight tickborne disease and, if so, what exactly the mice should be resistant to. Esvelt said getting community input and approval was a crucial first step. Individuals can always decline to take a pharmaceutical recommended by their doctors, but “when we alter a shared environment, we are changing the lives of everyone who lives there in a way that they can’t opt out of.”
The proposal was well received, with residents asking that the white-footed mice be resistant ideally to both Lyme disease and ticks in general. “I love the community input aspect of all this,” Telford said. “In contrast to my past efforts, where I come in and tell people that they need to do something, we have these residents involved from the very start, and hopefully that will make all the difference.”
Since 2016, Telford has provided the MIT lab with white-footed mice immunized against Lyme. After many twists and turns in trying to demystify the molecular biology of the native species, the researchers have isolated antibodies that provide protection against the Lyme bacterium. According to Mice Against Ticks project manager and research assistant Joanna Buchthal, the team now expects to identify additional antibodies that are even more broadly protective against Lyme disease, as well as ticks themselves, within a year.
Meanwhile, to find sites for field trials, Telford is researching which mostly uninhabited islands off the East Coast best mimic Lyme infection rates seen on Nantucket and Martha’s Vineyard (with permission of those islands’ owners). The trials will provide real-world data on success rates and potential side effects—all of which will be shared with Nantucket and Martha’s Vineyard residents at ongoing community meetings. It’s really like an “infrastructure project, in that we’ll succeed or fail based on the strength of our community engagement,” Esvelt said. “But it’s exciting to be pioneering not just a possible solution to Lyme disease, but also an entirely new way of developing biotechnologies—with all the science done out in the light.”
If all goes according to plan, the researchers hope to introduce the genetically engineered white-footed mice to Martha’s Vineyard and Nantucket within seven years. “If this works and we can actually modify mice so they are no longer reservoirs for Lyme disease in this model system we have in our own backyard,” Telford said. “I would want to see this approach applied to global health problems, like Lassa fever in West Africa or hanta virus in Latin America, where public-health resources are fairly limited and there are known critical rodent reservoirs.”
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