Three years ago, biological engineer Kevin Esvelt proposed a new way to genetically modify entire populations of organisms in the wild. Esvelt and his colleagues at Harvard University's Wyss Institute for Biologically Inspired Engineering suggested that some major ecological problems could be solved with self-propagating genetic devices called gene drives, which carry human-designed genetic modifications into wild populations. Gene drives, which have the potential to suppress the growth of wild populations, could be used against a variety of harmful species, ranging from malaria-bearing mosquitoes and agricultural pests to invasive species that threaten endangered native animals and plants in many areas around the world.
Esvelt has since changed his mind. As serious efforts to develop gene drives get underway, Esvelt, now a professor at the Massachusetts Institute of Technology's Media Lab, is warning that if we use this technology to solve ecological problems, the cure may end up being worse than the disease. Writing with New Zealand biologist Neil Gemmell, Esvelt worries that "a standard, self-propagating ... gene drive system is likely equivalent to creating a new, highly invasive species: both will likely spread to any ecosystem in which they are viable, possibly causing ecological damage." He now believes that his earlier recommendation to develop gene drives for conservation projects "was a mistake."
There was one conservation project in particular that prompted the warning by Esvelt and Gemmell: New Zealand's Predator Free 2050 project, an ambitious public and private effort to eradicate the rats, possums, and stoats that have pushed many native New Zealand species to the brink of extinction. The New Zealand government spends $70 million annually in its efforts to control these invasive species, which didn't exist on the country's islands before the arrival of humans, about 700 years ago. After nearly half a century of effort, New Zealand has managed to remove the invasive mammals from only about 10 percent of its offshore island area. For the Predator Free project to even come close to meeting its goals by 2050, New Zealand is going to need more effective tools—which is why some scientists think New Zealand should consider gene drives.
On paper, gene drives sound like an ideal pest control technique. Gene drives use a trick of molecular biology to spread a harmful mutation throughout a population. It doesn't spread infectiously, like a virus, but, rather, from parents to offspring. By introducing some gene drive-carrying animals into the wild, the harmful mutation would spread widely after a few generations. New Zealand could release a few hundred rats carrying gene drives with a mutation that causes sterility. Those rats would breed with the wild population, and, after a few generations, much of the rat population would be unable to reproduce. Eventually, rats would become extinct in New Zealand.
Since gene drives are passed only from parents to offspring, they affect only the target species, unlike traps or poisons. Gene drives, also unlike poison, don't kill or injure the animals, and thus are more humane. And because gene drives are self-propagating, they could potentially achieve more success than conventional pest control methods, for less money and effort. One analysis showed that, by releasing a relatively small number of gene drive-carrying rats into the wild each year, New Zealand officials could drastically reduce the rat population within a few years, and completely eradicate it within a few decades. Because of these advantages, a group of wildlife biologists from New Zealand and the United States argued that gene drives represent "a potentially transformative advance providing species specificity not readily achievable with any other technology."
At this point, gene drives designed to eradicate New Zealand's rats, possums, and stoats are no more than a suggestion. But it's a suggestion that is almost certainly technically feasible, thanks to the rapidly developing capabilities of CRISPR genetic engineering technology. And so, according to Kevin Esvelt, "now is the time to be bold in our caution." The question is not whether gene drives will work, but whether they'll work too well. Invasive species like New Zealand's rats originally arrived thanks to human intervention—and we should expect that humans, wittingly or not, will carry gene drive-bearing rats back out of New Zealand. Invasive species are invasive. This means that, according to Esvelt and Gemmell, we should not put gene drives into any animal "unless international spread is the explicit goal."
Bringing down the world's population of rats may not sound like a terrible idea. Rats, which are originally native to Central Asia, are invasive across the world. But the decision to eradicate the world's rats shouldn't be left to the officials of a single country. Furthermore, a species that is invasive in one place is a native part of the ecosystem somewhere else. Perhaps most of the world could do without rats, but New Zealand's problematic possums were brought over from Australia—and a gene drive that eradicates New Zealand possums could easily spread and damage Australian ecosystems where possums are native.
Gene drives, according to Esvelt and Gemmell, "should only be built to combat true plagues such as malaria, for which we have few adequate countermeasures and there is a realistic path toward an international agreement to deploy among all affected nations." To put together an international agreement like that requires a lot of trust— trust that scientists will follow agreed-upon safety measures, trust that governments will be transparent about the experiments being done, and trust that the members of the affected communities will have a voice in the decision-making. One bad incident—for example, a rogue gene drive developed in one country that ends up harming another—could generate a backlash, tarnishing a technology that has the potential to achieve some genuine good in the world.
Esvelt is right to be worried, because an international agreement to apply gene drives against one of the world's most damaging infectious diseases is on the horizon. An international group called Target Malaria, sponsored by the Bill & Melinda Gates Foundation, is trying to develop gene drives that will greatly reduce the population of malaria mosquitoes. They hope to begin trials in three countries in sub-Saharan Africa, where conventional disease-fighting strategies have failed, and where hundreds of thousands continue to die from malaria each year. A failed gene drive experiment elsewhere could threaten Target Malaria, even if Target Malaria's project didn't suffer from the same flaws.
Successfully combating malaria is important in its own right, but there are even broader implications here. For the past three decades, our society's conversation about genetic engineering has been dominated by arguments over genetically modified foods, which were developed with the relatively crude technologies of the 1990s. The genetic engineering technologies introduced in the past five years are the genetic equivalent of personal computers—what can be done, and who can do it, is about to change completely. Gene drives to control pests, genetically engineered cells to treat cancer, and genetic editing of human embryos are just a few of the applications we'll see in the coming years. We're more likely to reap the benefits of these applications if we heed Esvelt's call for caution, trust, and transparency.