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Scientists Can Now Genetically Modify Organisms in the Wild

A new genetic engineering technology could help fight malaria, but can it be used responsibly?
(Photo: turkletom/Flickr)

(Photo: turkletom/Flickr)

When a team of Chinese scientists announced last spring that they had edited the genes of human embryos using the powerful new gene editing technology known as CRISPR/Cas9, the world suddenly discovered that the dystopian possibility of "designer babies" was no longer an unrealistic fantasy, but rather a technically achievable possibility that must be reckoned with. A discussion of the ethics of genetically modified human embryos had barely started before another ethically fraught application of CRISPR/Cas9 made its debut. The new technology, known as a gene drive, is genetic engineering on an entirely new scale: It makes it possible not just to modify organisms in the laboratory, but to edit the genes of entire populations in the wild.

Gene drives aggressively spread a favored version of a gene throughout a population by using the genetic equivalent of a two-headed coin to skew the normal odds of heredity. Individuals of sexual species have two different copies of their genes, but because it takes two parents to reproduce, each individual passes on only one copy to their offspring. Which of the two copies of a gene—such as the brown or blue version of a gene affecting eye color—gets inherited is normally a toss-up. Gene drives are cheater genes that make this genetic coin toss always turn up heads—they ensure that one particular copy of a gene is always inherited by the next generation, and not the other. As a result, one version of a gene is "driven" to dominance in the gene pool, while other versions disappear and one particular trait becomes nearly universal in the population.

Gene drives are cheater genes that make this genetic coin toss always turn up heads—they ensure that one particular copy of a gene is always inherited by the next generation, and not the other.

Gene drives occur naturally among a wide range of organisms, including plants, insects, and even mammals. But gene drives also offer a way to widely propagate lab-designed genetic modifications. Researchers could make an organism with some usefully engineered gene attached to a gene drive, and then release that organism into the wild. After several dozen generations (which could be only a few years for rapidly reproducing species like some insects), nearly every member of a wild population would then carry that lab-designed genetic modification.

Given how controversial genetically modified crops and livestock are, the idea of deliberately editing the genes of an entire wild population probably sounds like something only a mad scientist would consider. But for more than half a century, scientists have seen gene drives as a potentially powerful tool to help solve a major global health problem: insect-borne diseases, especially malaria. Back in 1960, a team of researchers proposed using a gene drive to control mosquito population levels in areas where malaria is endemic. But the idea wasn't technically feasible until the past decade or so, when modern gene-editing technologies became sufficiently effective and researchers began efforts to build workable gene drives in mosquitos. Progress was slow, however, until 2013, when the powerful and simple CRISPR/Cas9 technology suddenly made editing genes easier than ever before.

Not long after CRISPR/Cas9 was introduced, a group of Harvard University genetic engineers noted that the new gene editing technology might finally lead to successful lab-designed gene drives. CRISPR/Cas9, they predicted, "is highly likely to enable scientists to construct efficient RNA-guided gene drives not only in mosquitos, but in many other species. In addition to altering populations of insects to prevent them from spreading disease, this advance would represent an entirely new approach to ecological engineering with many potential applications relevant to human health, agriculture, biodiversity, and ecological science." This wasn't an especially surprising claim to people who work in this field—it clearly was only a matter of time before someone did the obvious and used CRISPR/Cas9 to build a gene drive. But the Harvard group's goal was to draw attention to the issue and initiate "thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology."

The technology didn't stay theoretical for long. Late last year, two groups published papers describing working gene drives in two of the major mosquito species responsible for carrying the malaria parasite in Africa and Asia. The first group, led by Valentino Gantz and Ethan Bier at the University of California–San Diego, and Anthony James at the University of California–Irvine, engineered a gene drive carrying a pair of genes designed to kill the malaria parasite inside the mosquito.

The second group, led by Nikolai Windbichler, Andrea Cristanti, and Tony Nolan at the Imperial College London, developed a more brute force approach, building a gene drive that breaks an important mosquito gene and renders the females sterile—a strategy designed to decimate a mosquito population. Both groups reported that, when the genetically modified insects were crossed with wild ones, as much as 99 percent of the offspring carried the modified genes, a clear sign that the gene drives were working. These experiments were done in the lab and not the wild, so until there are field trials it is not clear how well these gene drives will actually work in a real natural population. But the technology is no longer hypothetical, and it is urgent that society consider the implications.

The scientists who are developing gene drives know how ethically loaded this technology is, and, to their credit, they are trying to put the issue out there for public discussion. Without buy-in by the public and government leaders, these tools have no hope of being used to achieve the health goals their designers are aiming for. In their paper, Gantz and his colleagues argue that "significant advances in regulatory structures and ethical models of community engagement are as important as the further scientific development of these technologies."

Back in 2014, leaders in this field called on American and international regulators to begin considering how gene drives should be regulated. Another group of scientists recently proposed strategies to prevent experimental gene drives from being accidentally released into the wild. A team of genetic engineers at Harvard developed a method to limit the spread of gene drives, and even overwrite them in order to reverse their genetic effects. And the National Academy of Sciences has convened a committee to review gene drives and develop policy recommendations.

But even if scientists and regulators come up with a safe and responsible approach to building and using gene drives, the technology poses one major challenge that may be almost impossible to solve. As the team of Chinese scientists who edited human embryos vividly demonstrated, banning or regulating an ethically controversial biotechnology in one part of the world doesn't prevent it from being used elsewhere. With a technology as simple and inexpensive as CRISPR/Cas9, gene drives can be developed by a small team of scientists almost anywhere. And because gene drives in the wild won't stop at national borders, nations could suffer the ecological consequences of a decision made by their neighbor. Even more worrying is the possibility that gene drives could be used for vigilante environmentalism, akin to the risky geoengineering schemes by rogue individuals who try to solve major environmental problems on their own.

Genetic engineering has become so inexpensive and simple that applications with major consequences for society and the environment are no longer the exclusive turf of large companies with the resources to develop them. Gene drives could allow us to modify our environment on a scale that is well out of proportion with the effort it takes to build them. This is good because we now have a new way to solve difficult health and environmental problems. But ensuring that genetic engineering is used responsibly is still an unsolved and urgent problem.