A community-guided genome editing project can fight Lyme disease

Kevin Esvelt of MIT addresses community members during a public meeting of the Nantucket Board of Health, called to discuss anti-Lyme disease strategies using transgenic mice.KAYANA SZYMCZAK FOR STAT

The epidemic of Lyme disease is an ecological problem of our own making: We have inadvertently altered our environment to maximize the number of infected ticks. The question today is whether we should consider altering the genomes of wild animals to undo that mistake.

If so, we should find the most minimal intervention that might solve the problem. We should actively invite suggestions, concerns, and guidance from interested local communities who know their own environments best. And we should initially observe the effects on mostly uninhabited islands.

That’s exactly what my colleagues and I aim to do with Mice Against Ticks, a community-guided project working to prevent tick-borne disease through genome editing.

The current Lyme disease epidemic is the unanticipated result of our desire to live near trees. The Northeast is more wooded today than it’s been for millennia, but our forests are fragmented by houses and roads. Fragmented forests benefit three species:

• Black-legged “deer” ticks, which feed three times in their lifetimes, enough to acquire and transmit to other animals the pathogens that cause Lyme and other diseases.
• Deer, each of which can host thousands of adult ticks that will collectively lay millions of eggs.
• White-footed mice, which are better at acquiring and transmitting tick-borne pathogens than any other animal.

By changing the environment to benefit ticks, deer, and mice, we’ve inadvertently supercharged the cycle of tick-borne disease transmission, creating a positive feedback loop: More ticks create more opportunities for transmission. More deer mean more ticks. And more mice mean more infected ticks.

In principle, we could throw that cycle into reverse by immunizing white-footed mice against Lyme disease. Of course, trapping and vaccinating all of the mice in the woods would be impossible. But it is possible to harness immunity genes that some white-footed mice naturally acquire the same way people do: When exposed to a new pathogen, the immune system evolves new genes that flag the enemy for destruction. By isolating the most effective Lyme resistance genes evolved by some white-footed mice, combining and editing them into the genome so they can be passed on to descendants, and releasing sufficient engineered mice into the woods, we could gift nearly all mice living in an area with strong inborn resistance to tick-borne disease.

Mice Against Ticks will live or die by the three cautionary guidelines outlined earlier:

Make the smallest possible change that could solve the problem. Since some mice already evolve anti-Lyme resistance genes naturally, just like all mice do when vaccinated, gifting local mouse populations with the same kind of immunity should minimize unintended consequences.

Seek advice from people who may know more. Science works by inviting others to challenge ideas. I believe the term “others” should include people beyond the scientific community, especially those who live in potential early adopter communities. The more skeptical you are, the more we want to hear why.

Start small and see what happens before scaling up. Many people across the country would like to put an end to Lyme disease tomorrow, but it would be premature to begin immunizing mice everywhere. It’s better to start with reversible trials on well-studied and sparsely populated islands that are small enough to remove all of the edited mice and reintroduce wild mice if necessary.

Our team approached the communities of Nantucket and Martha’s Vineyard in 2016, before we performed any experiments in the lab, to invite community guidance on whether and how to proceed. Were people interested enough for us to begin research, knowing that the benefits would be many years away and might eventually require releasing 100,000 genome-edited mice into the woods? Remarkably, the answer was a resounding “yes.” But when asked whether we should stick as close as possible to what’s already found in nature, even if that makes the intervention slower, less effective, and requires more mice to be released, people were, and are, divided. Conversations over the years suggest that an apparent majority prefer that we err on the side of simple and natural when possible.

How well our approach works — and whether there will be any ecological side effects — can’t be known until we test it. That’s why we’ll need federal and state regulators to carefully examine the mice and approve field trials on the small, mostly uninhabited islands that have already volunteered for the privilege. Independent ecologists will evaluate the trial results and report to the communities of Nantucket and Martha’s Vineyard, which will decide whether or not to proceed using their own systems of governance. If effective, the same resistance genes could be used for disease prevention on the mainland.

We expect to continue to learn from residents about what is and isn’t important to them, and also about what we should be watching for and designing for. We’ve already had citizens point out potential outcomes we hadn’t anticipated that might change how communities decide to introduce resistance. It’s possible that we might come across something that fundamentally challenges public support for the project. If so, we walk away: your environment, your call.

My personal hope is that the Mice Against Ticks model, in which researchers openly approach communities before beginning experiments and agree to be guided by a steering committee of local residents, will become the gold standard for all research intended to engineer wild organisms and introduce them into the shared environment.

This may not seem very important if scientists are just immunizing the neighborhood mice. But Mice Against Ticks is noteworthy for not using the most powerful technology available: Recently invented “gene-drive” methods are capable of single-handedly spreading genome alterations from just a handful of introduced organisms to the entire species. That’s not the kind of technology we want scientists to be developing on their own and in secret.

Even if we differ on whether to release engineered Lyme-resistant mice into the woods, ensuring that ecological engineering proposals start small and invite community guidance is a project everyone can support.

Kevin M. Esvelt, an evolutionary engineer and assistant professor at the MIT Media Lab, is an inventor of CRISPR-based gene drive and a founder of the Mice Against Ticks project.

A community-guided genome editing project can fight Lyme disease