In 2011, experiments that allowed the potentially deadly H5N1 flu virus to spread between mammals ignited intense discussions about whether such research should be done at all, much less published. But most of the debate occurred after the research had been carried out.
Kenneth Oye, a social scientist at the Massachusetts Institute of Technology in Cambridge, thinks that the discussion needs to take place before the lab work starts. In an article appearing online today in Science, he and nine colleagues have outlined what they think needs to be done about an emerging technology called gene drive.
Gene drive involves stimulating biased inheritance of particular genes to alter entire populations of organisms. It was first proposed more than a decade ago, and researchers have been developing gene drive approaches to alter mosquitoes to slow the spread of malaria and dengue fever. Although progress has been quite slow, recent advances in gene editing could lead to a rapid application of gene drive approaches to other species, Oye and his colleagues predict. To avoid a repeat of the H5N1 brouhaha, Oye says, “what we would really like to see is good, well-informed discussion of the benefit and potential risks specific to the particular application, species, and context. … We need to do it before people get that hot about it.”
Oye is not alone in calling for government agencies, scientists, and the general public to figure out how to regulate the release of mosquitoes and other organisms with gene drive alterations. In June, the WHO Special Programme for Research and Training in Tropical Diseases issued guidelines for evaluating genetically modified mosquitoes. A year earlier, the European Food Safety Authority came out with a six-step protocol for environmental assessments of all genetically modified organisms. “People are beginning to think through these issues,” says Austin Burt, an evolutionary geneticist at Imperial College London.
Burt pioneered the idea of using gene drive to benefit humankind. Researchers had already shown that certain “selfish” genes could increase in frequency in each generation, and Burt suggested that it should be possible to create a selfish gene that, for example, would make a mosquito resistant to infection by the malaria parasite or cause the production of only male offspring. (Fewer females means fewer biting insects and, subsequently, lower malaria transmission rates.)
Introducing these genetically modified mosquitoes into the wild should, over time, cause the modified gene to spread throughout the population and interrupt malaria transmission. He and researchers at about 10 institutions are working on the idea, but he says they are at least 5 years from testing it in the field.
One boon has been the rapid spread of a new gene-editing technique called CRISPR-Cas9. It’s worked well for deleting, adding, or modifying genes in all 20 species tested to date, including humans, says Harvard University’s George Church, a co-author who wants to use CRISPR to treat human disease and improve crops. Working with Church, Harvard’s Kevin Esvelt and colleagues are using CRISPR to improve gene drive technology.
The National Science Foundation, working with the Woodrow Wilson International Center for Scholars, has sponsored several workshops in which Oye brings together diverse groups to think about emerging technologies. Among the three dozen participants, someone from the environmental advocacy group Friends of the Earth might be sitting next to a representative from the J. Craig Venter Institute that develops modified organisms for a range of applications. Oye hopes that the Science article will expose many more scientists to the idea of gene drive technology. In addition, in eLife today, Church’s group describes the potential of CRISPR to speed up gene drive technology, as well as the possible limitations of gene drive approaches. “In the case of [g]ene drives, it is the pests which are engineered and the solution spreads automatically,” Church says.
The paper presents no results, but Church says that Esvelt is well into testing CRISPR-generated gene drive approaches in yeast, nematodes, and mosquitoes. The goal is to test the potential of the altered genes to spread to other species and other populations. “We want to be absolutely sure before releasing [gene drive modified organisms] that it’s not going to escape from the species in which we are putting it,” Burt says.
There are other concerns as well, says James Collins, an evolutionary ecologist at Arizona State University, Tempe, who co-organized the workshops with Oye and is another co-author on the Science paper. Gene drive technology may one day make it possible to drive invasive species to extinction or to make herbicide- or pesticide-resistant pests susceptible again. But despite the best efforts of scientists to improve health and agriculture, Collins says, “we’ve learned it’s still possible for evolution to take the system in a direction that’s not planned.” To avoid such a disaster, he adds, “we still need a basic understanding of the genome and how genes move through ecological systems and a basic understanding of what the loss of species means to a community.”
He and Oye hope funding agencies will support research aimed at finding answers to those and other important questions before the first gene drive mosquitoes take to the sky.
*Clarification, 18 July, 1:24 p.m.: This article has been updated to clarify that the Woodrow Wilson International Center for Scholars played a role in the workshops.