Published On June 13, 2017
GENETIC TOOLS OFFER A NEW HOPE FOR MANAGING MOSQUITO-BORNE DISEASES, which cause more than a million deaths every year. A few thousand mosquitos, for instance, can be engineered to carry a strategic mutation—one that causes the insect’s offspring to be sterile, say—then set loose in the wild to breed. As those mutations are naturally spread in the population, researchers should see the spread of mosquito-borne diseases slow down.
Global agencies are inching toward approving these mutant armies, which should not carry the same terrible ecological side effects of chemical pesticides. But one recent twist in genetic pest control has raised more serious concerns. It’s called a gene drive.
A mutation is normally passed down to offspring only 50% of the time, since every organism receives a mix of genes from both parents. But a gene drive ensures the mutant gene will get passed along more often—up to 100% of the time. Researchers accomplish this by placing not only the desired mutation in the DNA but additional code that promotes the chances of the offspring receiving the new gene.
That boost ensures a rapid “driving” of the mutation, a geometric cascade in any species that reproduces quickly. Under ideal conditions, a single mosquito with a gene drive could see its mutant gene passed along 10,000 times in the span of about a year or two.
Some worry that this powerful technology might jump the track once it is set loose. Gene drive mutations might cross over to closely related species that weren’t the target of the attack, or the gene might mutate on its own, quickly driving unintended mutations.
Who, then, would govern the use of gene drives? The regulatory landscape is complex and somewhat muddy. The Food and Drug Administration, the U.S. Department of Agriculture and the Environmental Protection Agency provide a coordinated framework for regulating biotechnology, an umbrella classification that covers all genetically modified organisms. But which agency would have jurisdiction in particular cases remains unclear, says Arthur Caplan, professor of bioethics at New York University School of Medicine.
The EPA regulates pesticides and rodenticides, and genetically modified insects might be considered a kind of pesticide. The USDA, meanwhile, would have a say in regulating organisms that might be a danger to crops. And the FDA clarified in January that all genetic modifications to most animals are subject to FDA regulation, because such changes meet the definition of a “new animal drug.” But the FDA has not yet addressed gene drives directly.
The U.S. Fish and Wildlife Services and the Department of the Interior should probably also have a say in how a gene drive would be regulated and deployed, says Caplan. And if the gene drive might somehow, through natural mutation or human interference, pose a threat to people, it would fall under the purview of the Centers for Disease Control and Prevention and the Department of Defense.
“People want clarity about who is responsible,” says Caplan. “That currently doesn’t exist.”
Regulating these mosquitos in the lab poses another regulatory quandary. Lab safety falls under the purview of Institutional Biosafety Committees, which are required for all federally funded labs and are accountable to the National Institutes of Health. So far, though, there aren’t any lab-safety requirements specifically for gene drives.
Safety advocates have started to step into this crowded landscape. Kevin Esvelt, an assistant professor of biological engineering at the MIT Media Lab and a gene drive pioneer, was part of a team that drew up stricter guidelines, published in Science in 2015, for labs carrying out gene drive research. But following them is, for now, entirely voluntary.
Esvelt also proposed oversight with more bite. Certain partners are critical to gene drive research—patent holders for necessary technology, foundations that fund the research and the journals in which it is published. These should all make their support conditional to public safety, he says, and require that gene drive projects publish the explicit aims of their research and also any plans for keeping their research contained to the lab.
So far, the Bill & Melinda Gates Foundation and the Open Philanthropy Foundation have expressed some support, says Esvelt. And the Broad Institute of MIT and Harvard, which holds a patent for the CRISPR-Cas9 technology used to create gene drives, is also setting the tone. A recent patent agreement with Monsanto, an agricultural biotechnology company, includes an explicit prohibition against the creation of gene drives.
George Church, a geneticist at Harvard Medical School and one of the co-authors of the Science guidelines, favors additional controls, including a registry for anyone who purchases the CRISPR-Cas9 technology. The genetic signatures of gene drives should be on file to identify the creator and establish liability in case of an outbreak. “It’s not sufficient to have people swearing they will do the right thing,” says Church. “You need surveillance.”
And regulations in the United States are just a first step, as mosquitos know no borders. The United Nations has yet to issue guidelines, although it recently declined a proposed moratorium on gene drive research. On a global level, the debate about its benefits and risks—and who should regulate them—has just begun.
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