Genetically Engineered Mice Could Fight Lyme Disease Off Cape Cod

February 7, 2017

The people of Nantucket have a problem. On the heavily forested island off the coast of Massachusetts, doctors report that as many as 40 percent of all households have been impacted by Lyme disease. While residents are desperate for a solution to the scourge, many are also staunchly opposed to the idea of reducing the island’s large and increasing deer population, a primary food source for the disease-transmitting ticks.

Kevin Esvelt, a Hertz Fellow and biologist at the Massachusetts Institute of Technology (MIT) Media Lab, may have a solution. Using a revoluntionary gene-editing tool called CRIPSR, he and his team could genetically engineer native white-footed mice, which are responsible for infecting most ticks, to be immune to Lyme disease. His team would take the antibodies mice have evolved in response to the pathogen and insert the genes into the mice’s genomes. If the community were to support releasing the genetically-engineered mice into the wild, it would theoretically break the transmission cycle of the disease further down the food chain from the deer.

“We’re making mice that are 100 percent white-footed mice, but can’t be reservoirs for tick-borne diseases,” Esvelt said. “We’re not introducing DNA from any foreign species. All we are doing is giving these mice, and all of their descendants, the protection that previously-exposed mice managed to evolve.”

Islanders are listening. Esvelt has held several meetings with residents of Nantucket and neighboring Martha’s Vineyard to present his idea, taking an open source approach to the research. He feels opening up his lab books, sharing grants and offering transparency into his lab’s finances is the only way to do science that might impact the world outside the lab.

“I don’t think people have the right to tinker behind closed doors with systems that could affect the lives of many people,” Esvelt said. “If Monsanto did it one way, we’re going to do the opposite.”

Hertz Fellow Kevin Esvelt
Hertz Fellow Kevin Evselt, assistant professor in the MIT Media lab and leader of the Sculpting Evolution Group at MIT, seen here at a Nantucket community meeting discussing how CRISPR could nearly eliminate Lyme disease on their island.

Esvelt’s openness and willingness to let residents decide how the experiment will be conducted has helped ease residents’ fears and even changed the minds of some who had initial misgivings. In fact, Esvelt said he’s been disappointed there haven’t been more skeptics to point out things he might be missing.

“I thought we were going to run headlong into a wall of people saying ‘No, we just don’t want engineered mice,’” Esvelt said. “In reality, people are saying, ‘You know what, I’m uncomfortable with the notion of engineering the environment, but we have a serious problem, we don’t have any other good solutions, and we respect that you’re being open and talking to us before you do anything.’”

It will be a lengthy process to implement Esvelt’s proposal. First, Esvelt and his team will begin engineering mice to make them immune to both the Lyme disease pathogen and tick saliva. Next, he must gain authorization to release about 1,000 on an uninhabited island to test how long it will take for the mice to transmit their antibody-encoding genes to every other mouse on those islands.

Esvelt and his group are already starting to select the heartiest antibodies and the associated genes that encode them. Once identified, they will be injected into mice, establishing a colony at MIT, and work will begin on ways to engineer the mice genome. Esvelt estimates it will take up to 200,000 mice to overtake the existing populations on Nantucket and Martha’s Vineyard. The team will also create an independent safety monitoring board to examine Lyme disease in ticks over time and study the impacts of the mice on other animals.

If the communities are supportive and all goes well, the team would release the engineered mice in about seven years. Esvelt will continue to meet periodically with residents throughout the process.

“The very nature of this process means we must keep in close touch with the community to report on what we’re doing and ask for guidance in cases where there’s a decision fork,” Esvelt said. “Questions like which island do we choose and who will be on the monitoring board? What is ‘independent enough’ for the independent safety monitoring board? These are important questions and we will need community feedback to move forward.”

As head of the Sculpting Evolution group at MIT, Esvelt is acutely aware of the potential pitfalls of genetic engineering on nature and society. His group is not only focused on the science and biology of living systems, but also on the evolution of cultural perceptions of genetic engineering and shaping assumptions over time.

Esvelt’s current focus remains on the CRISPR gene drive, a technology he helped develop, that can edit the genes of an entire species by driving them through a population over numerous generations. There are only a handful of applications for a global gene drive, Esvelt said, such as eliminating malaria. All other applications require something local that doesn’t spread indefinitely.

To address that issue, Esvelt is also working on “daisy drive” technology, a CRISPR system split into multiple pieces and spread on both sides of genome. It’s a way of teaching the DNA to count generations, he explained, essentially imposing a ‘genetic fuel limitation’ upon engineered evolution. His goal is to someday build a daisy drive that can allow a community to alter its own environment while leaving the neighboring community untouched, and ensure that we can restore entire populations to their original wild settings if needed—regardless of the initial genetic change or its source.

Esvelt is proceeding cautiously with gene drive technology. He follows two self-imposed rules because the consequences are so unpredictable: make the smallest possible change to solve the problem and start small, scaling up only if warranted.

“I feel that scientists should hold themselves morally responsible for all the consequences of their work,” he said. “Like it or not, I was the one who told the world what could be done with CRISPR gene drives, so I hold myself responsible for the consequences. That means I need to do what I can to ensure the outcomes are beneficial. One of those things is figuring out how society should decide whether, when, and how to use something like that.”