Although it may take 5 years or more before researchers will be ready to try a controversial technology for eradicating or replacing populations of pests and vectors in the field, today a National Academies of Sciences, Engineering, and Medicine committee urged researchers, funding organizations, and regulatory agencies to waste no time in coming up with ways to deal with the societal and regulatory issues surrounding this technology, called gene drive. Its report, Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty and Aligning Research with Public Values, stresses that although gene drive offers great promise for agriculture, conservation, and public health, neither the science nor the current regulatory system is adequate to address the risks and requirements of gene drive–altered organisms.
Gene drive is a natural phenomenon whereby a certain version of a gene is passed on preferentially to the next generation and thus can quickly spread throughout a sexually reproducing population. For decades, researchers dreamed of harnessing gene drive to control pests or disease-carrying organisms. For example, by biasing inheritance toward the production of one sex over another, altered sex ratios might eventually cause a population to peter out. Thus, gene drive could be used to reduce malaria transmission in humans—or in endangered birds (see image, above)—by making the mosquito vectors incapable of spreading the malaria parasite or even eliminating the insects altogether.
The approach hadn’t seemed within close reach until geneticists last year demonstrated gene drive in fruit flies and yeast by harnessing a gene-editing technique called CRISPR/Cas9. The experiments set off a debate about the safest way to do gene drive experiments in the lab and helped prompt the Defense Advanced Research Projects Agency and the Bill & Melinda Gates Foundation to support the academies’s study. It's one of several efforts inspired by the fast progress made possible by CRISPR: Another CRISPR-inspired academy study is looking at genome editing in animals, and last year the academies held a summit on genome editing in human embryos.
The new 216-page document calls for more ecological and population dynamics research, more thorough ecological assessments, new types of regulations, and greater coordination among funding agencies to make sure the research needed to address gaps in knowledge is done. It also recommends greater public involvement in early stages of the technology’s development and approval. And because one widely discussed application is to introduce gene drive–modified mosquitoes in malaria-prone developing countries, the academies cautions against doing so until the countries involved are equipped with the expertise and infrastructure to deal with these trials. Based on this report, “there is a lot of work that has to happen before we get to the point of releasing a gene drive [organism] into the environment,” says Todd Kuiken, an environmental scientist with the Wilson Center in Washington, D.C.
The few successful proof-of-concept experiments conducted in the lab to date are not sufficient to consider releasing gene drive–modified organisms into the environment, the report concludes. Much more research is needed on how gene drive would work under different environmental conditions or whether the selected genes would spread to other species or change in some way over time. In some scenarios, gene drive would cause a population to go extinct, and data are lacking on how the loss of a species would affect its local ecosystem. Yet the report “doesn’t talk about where that money will come from and who will do that research” in population genetics and ecosystem dynamics, Kuiken notes. But funders are well aware of this need, says Gates Foundation scientist Scott Miller. He notes that the foundation is starting to support the development of ecological assessment protocols in Africa and plans to do more.
Risks will likely vary by species and by each particular gene-drive modification, so the academies calls for a case-by-case evaluation of future gene-drive organisms. They advocate the use of “phased” trials as outlined in 2014 by a World Health Organization guidance framework that covered the use and development of genetically modified mosquitos. Under this framework, testing should move from the lab to natural environments in confined conditions before open release trials. “There's a strong urging of caution, but they recognize the promise of the science is sufficient to go ahead with it,” comments vector biologist Anthony James from the University of California, Irvine, who has shown gene drive is possible in mosquitoes.
Other organizations are looking at different aspects of gene drive. The J. Craig Venter Institute is finishing an analysis funded by local California groups. “Our focus is probably more nuts and bolts” about regulatory issues, such as how to actually design contained field trials, gather the information in a natural environment, and coordinate regulations among local, regional, national, and international agencies, says ecologist Robert Friedman, who is vice president for policy at the J. Craig Venter Institute in San Diego, California. He calls it “a very complex undertaking,” but adds, “I’m not a pessimist who says it can’t be worked out, but we would be wise to starting working it out now.”
Just yesterday, the U.K. House of Lords began debating the pros and cons of starting field trials of genetically modified insects, not necessarily in the United Kingdom, after a December 2015 House of Lords report advocated that the country take a leading role in developing these technologies. The report also pointed out, however, that the E.U. regulatory regime for genetically modified organisms was not “functioning effectively.”
Gene drive is so different from other technologies involving genetic modification that it requires a whole new way of thinking about how to evaluate and regulate it, says Jennifer Kuzma, a natural and social scientist at North Carolina State University (NCSU) in Raleigh who helped organize a February workshop there. To date, regulations have centered on containing genetically modified organisms. But with gene drive the goal is for the modification to spread. “It makes it more important to use a wider range of voices to think through the impacts,” Kuzma says.
The academies’s report is generally getting good reviews. “It's great that they are doing this and we are going to need to build on it so that we can come up with a good and acceptable testing pathway for these organisms,” says gene drive pioneer Austin Burt at Imperial College London. Helen Wallace, the director of GeneWatch UK, a biotechnology watchdog group in Buxton, applauds the report for recognizing that gene drive technology may have harmful effects on other species. However, she faults the report for not addressing potential conflicts of interest that could lead researchers and companies to push for the commercialization of these technologies before the risks are well understood. Nonetheless, Kuiken concludes, “I think [the report] is going to have some staying power.” Committee member Jason Delborne, a social scientist at NCSU, agrees. "It's not the definitive word about whether gene drives are going to happen or not happen," he says, "but it's already having an impact in terms of fostering a broader conversation about the potential benefits and harm."
“The report rightly identified governance as a critical issue but it does not go far enough in advocating democratic engagement,” says Zahra Meghani, an ethicist at the University of Rhode Island, Kingston. “The development, risk assessment regulation, and use of gene drives should be based on public dialog, public deliberations, and public decision-making. Marginalized groups or communities that could be directly or significantly affected should have a key place at the decision-making table.”