Gene editing to stop Lyme disease: caution is warranted

When I first learned about Mice Against Ticks, I was shocked but also intrigued — shocked by the audacity of Kevin Esvelt’s plan to genetically engineer a mammal native to the United States, but curious about whether the project could prevent Lyme disease. The outcome of this radical intervention might influence how society views the acceptability of altering the genes of other animals, and perhaps even our own.

As an academic ecologist, I’ve spent the past three decades studying effects of genetically engineered organisms like Roundup-Ready crops on wild species. With the recent advent of the gene-editing technology known as CRISPR, biochemical engineers have bold, new aspirations that include tinkering with the genes of wild species in order to sculpt evolution, or even eradicate unwanted species from entire continents using a technique called gene drive.

Mosquitoes that carry malaria and other disease-causing pathogens are the focus of several gene-editing efforts. Now the white-footed mice of New England are another target. The persistence of Lyme disease depends on intricate ecological relationships among ticks, small mammals, and deer. Many researchers consider white-footed mice to be a major reservoir for Lyme disease because they harbor the bacteria that cause it, are very abundant, and are often bitten by black-legged ticks (deer ticks), which then infect people.

Esvelt and his collaborators hope to engineer mice to make them resistant to Borrelia burgdorferi, the microbe that causes Lyme disease, and possibly to black-legged ticks as well. Their ultimate goal is to release thousands of these genetically engineered mice, first on largely uninhabited islands. If the experiment works, they would then replicate it on Nantucket and/or Martha’s Vineyard, and possibly the mainland — pending, of course, sufficient research progress, regulatory approvals, and public support.

Commendably, the team has sought comments and advice from residents of Nantucket and Martha’s Vineyard since 2016, and they are eager to obtain feedback from others during each stage of this ambitious, long-term project.

My main concerns about Mice Against Ticks center on how well independent ecologists and evolutionary biologists will be able to evaluate its long-term safety and likelihood of success. Once the genetically engineered mice are allowed to breed freely outdoors, it will be difficult — if not impossible — to recreate the original, non-engineered mouse populations if something goes wrong. Resistance genes that have been introduced by genetic engineering could persist indefinitely in wild mouse populations, so it’s essential that we understand and avoid possible risks well in advance of any planned releases.

The ecological effects of releasing genetically engineered mice into the wild could range from negligible to harmful. What if the genetically engineered mice turn out to be much more prolific or aggressive than their unaltered counterparts? Or what if other tick species and pathogens become more abundant following this intervention? Predicting the ecological effects of island-wide introductions of genetically engineered mice will be challenging, as I recently described in the journal BioScience.

Ecologists think of white-footed mice as a hub species because their populations affect, and are affected by, interactions within an interconnected network of many other species. These small creatures eat seeds, fungi, insects, and other invertebrates, and are in turn eaten by snakes, owls, hawks, bobcats, foxes, coyotes, and other animals. Although it’s simplistic to argue that there is an idealized balance of nature, we need to understand how all of these species can affect each other’s abundance, keeping in mind how often humans have caused harm by introducing wild animals and plants into novel situations. So it is clear to me that careful attention to possible unintended consequences of Esvelt’s proposal is warranted.

Another concern I have is whether the project can actually succeed. Will it lead to a measurable, long-term reduction in the numbers of the Lyme-infected ticks that transmit the disease to people? What if the introduced genetically engineered mice are inferior to local wild populations in their ability to survive, compete, and reproduce, causing the new resistance traits to be lost? Or could other reservoir species for Lyme disease —shrews, voles, rats, chipmunks, squirrels, and ground-foraging birds — sustain the Lyme transmission cycle perfectly well on their own? What kinds of ecological or epidemiological data would be needed to show that the intervention is working as intended, and how feasible are such studies? It’s important to consider these questions in advance to maximize the chance of success.

I am optimistic that concerns about this project can be taken into account as it moves forward and as ecologists and others continue to weigh in on expected benefits and risks. At this early stage, there is ample time for debate and research to answer key questions.

Although I’m inherently cautious about genetically engineering wild species, in some cases such interventions may be relatively safe, beneficial to human health, and worth the presumed risks. Perhaps this will be one of them.

Allison Snow is professor emeritus in the Department of Evolution, Ecology, and Organismal Biology at Ohio State University.

Gene editing to stop Lyme disease: caution is warranted