In recent years, scientists have begun using the gene editing tool Crispr to experiment in the laboratory with altering embryos and changing the DNA of animals. But the consequences of using the technology outside the lab are hard to predict—and potentially enormous. As a result, a worldwide debate is underway about how much say ordinary citizens should have over the use of CRISPR in their communities. Earlier this month, Richard Johnson, a biologist who runs the Martha’s Vineyard Tick-Borne Illness Reduction Initiative, attended a discussion of Mice Against Ticks, an ambitious project working on using the CRISPR gene editing tool to create mice resistant to the bacteria that causes Lyme disease. Someday, the genetically engineered mice might be released on Martha’s Vineyard and neighbouring island Nantucket, where they could breed with the local mice and pass on the immunity to their offspring. Ticks that feed on the mice would not become infected, so they would not transmit the pathogen to humans, lowering the incidence of the disease. Mr Johnson believes that the scientists can find a way to make the disease-resistant mice. For him, it’s the ethical and political questions about the project that is hard to answer: Should the scientists do it, and who gets to decide?
CRISPR, which stands for clustered regularly interspaced short palindromic repeats, isn’t the first new technology to pose such complicated questions. But CRISPR offers “the potential to control evolution and change future species,” says biochemist Kevin Esvelt, an assistant professor at the Cambridge, Mass.-based MIT Media Lab, where Mice Against Ticks was born. CRISPR is the immune system of bacteria. Scientists adapted Crispr and the Cas9 enzyme that it produces to serve as a tool to edit DNA in plants, animals and humans. Researchers soon realised that CRISPR might be used not only to edit or repair genes of people living with diseases but also to edit embryos, changing the DNA of future generations. It could also be used to create a so-called “gene drive,” spreading engineered genetic changes through populations of wild animals but also altering the environment in unpredictable ways. With so much at stake, Dr Esvelt says, scientists must not make such decisions by themselves.
At the event on Martha’s Vineyard, Dr Esvelt recounted how, historically, scientists often developed new technologies behind closed doors, without meaningful input from the people most likely to be affected by their use. By the time the public was asked to weigh in, he had said, it was usually too late to influence the direction of the science. With CRISPR, Dr Esvelt and his collaborators see an opportunity to take a different approach—a chance not just to do powerful science but to test new ways of discussing and deploying it. They found that when scientists and communities work together, there can be unexpected consequences. Last year, a group of academics invited Dr Esvelt to attend a workshop they were holding in New Zealand to discuss, among other things, the possible use of gene drives as a tool in conservation. New Zealand has launched an ambitious plan to rid the country of predators such as rats, stoats and possums that have decimated native flora and fauna. CRISPR is one of the technologies offer a potential solution.
Dr Esvelt gave a presentation about his research on a form of CRISPR gene drive that he is developing called a “daisy drive.” He thinks that the daisy drive is potentially a safer technology than a standard CRISPR gene drive because the changes are engineered to be passed on only for a limited number of generations, not to spread indefinitely. The concept has not yet been tested in a field trial. Among the people, Dr Esvelt met in New Zealand were members of Te Tira Whakamataki, or the Maori Biosecurity Network, a group of Maori elders, academics, tribal leaders and others interested in ensuring that the Maori have a voice in biodiversity issues. Melanie Mark-Shadbolt, CEO of the network, says that they liked Dr Esvelt’s idea of co-developing research and new technologies with community input. “We want to be active participants in research, not subjects,” she says. Shortly after the visit, Dr Esvelt and a New Zealand collaborator, Neil J. Gemmell of the University of Otago, published a paper in the journal PLOS Biology, laying out their concerns about the potential environmental consequences of standard CRISPR gene drives. The paper caused a backlash, say researchers in New Zealand because some felt that the authors implied that the actual use of gene drives in New Zealand was imminent rather than hypothetical. Ms Mark-Shadbolt felt blindsided. “When he met with us, he should have said, there is a paper coming out that talks about New Zealand and conversations I am having about gene drives, would you like to take a look?” she says. Dr Esvelt took the criticism to heart, and in January issued a public apology on his blog and in Medium. He agreed that he should have offered the Maori a chance to make suggestions while the paper was being revised. Reflecting on the experience, Dr Esvelt says, “I made the same mistake concerning the local political environment that we’re hoping to avoid with the natural environment: our lack of understanding leading to unwanted side effects.”
On Martha’s Vineyard and Nantucket, Dr Esvelt’s plan for community partnership has been on a surer footing so far. Even there, however, the outcome is not certain. Regulatory approval is not enough, the scientists believe. They also have promised not to release the genetically altered mice without approval from the communities. The prospect is still years away, but Carrie Fyler, a biology teacher at the public high school in Martha’s Vineyard and one of the representatives on the Mice Against Ticks steering committee, says that some wonder what a vote on the issue might look like. Would 51% be enough to move forward or would it require everyone to agree? As she says, “You can’t have a single town opting out, because mice don’t know town lines and will cross them.” At the meeting in Martha’s Vineyard in July, one of the ethicists pointed out that discussions about whether or not to use a scientific advance often turn on assessments of potential risks and benefits. Perhaps, the ethicist suggested the quality of public engagement and depth of community involvement in making decisions should also be considered. On every seat at the meeting was a pamphlet that Dr Fyler’s students had created to explain ticks and tick-borne illness in language that they and their parents could understand. Dr Fyler says that she reminded her students, “Whatever happens, it won’t be the scientists determining what will happen, it will be us.
Credit: Amy Dockser Marcus for The Wall Street Journal, 27 July 2018.