Why gene drives may never eradicate diseases or pests

A technology that could save thousands of lives is beset by ethical, legal and practical difficulties

THE chance that a sexually reproducing organism’s offspring will inherit a particular version of a gene from a particular parent is usually 50%. Gene drives are stretches of DNA that change those odds to favour one parent’s version of a gene over the other’s. If the odds are stacked sufficiently in favour of one version, then within a few generations it can become the only version still in circulation. Researchers realised soon after the discovery of gene drives in nature, half a century ago, that they might be made into powerful tools for eradicating diseases and pests. A drive spreading a gene that makes mosquitoes unable to host the parasite that causes malaria could eliminate the disease. If the drive makes female mosquitoes sterile, it could eliminate the insect altogether. Yet no such gene drive has been released into the wild. Why?

Early attempts to produce a synthetic gene drive focused on enzymes called homing endonucleases. They can insert copies of the genes that encode them into chromosomes, thus increasing both their number and the likelihood that they will be passed on to the organism’s progeny. Engineering these to do humanity’s bidding (by disrupting fertility genes, for example) proved difficult. That problem was solved in 2015, though, when Valentino Gantz and Ethan Bier of the University of California, San Diego, used CRISPR-Cas9, a recently discovered gene-editing tool, to make a gene drive that could be inserted anywhere in the genome of a fruit fly.

The ease with which gene drives could be made with CRISPR-Cas9 has, however, provoked fresh worries about the technology. These would need to be attended before gene-drive-carrying organisms could be let loose in the world. First, a gene drive that somehow hopped from a target species into the genomes of other animals might wipe them out before anything could be done about it. Researchers are therefore developing ways of switching off gene drives. Second, some ecologists worry about the side effects of exterminating entire species, however much people might like to see the back of them. Kill off malaria-carrying mosquitoes, for example, and animals that feed on them and their larvae will also suffer. Third, it is doubtful that all countries would agree to organisms harbouring gene drives being deployed on their soil. So there will need to be some means of confining the drive’s effects to a particular area. Initial trials of the technology are likely to be run on small, uninhabited islands. Finally, a study published earlier this year in PLOS Genetics adds to the evidence that those who would deploy gene drives against scourges such as malaria face another, more immediate, hurdle: such drives simply may not work. Just as insects and pathogens evolve resistance to new pesticides and antibiotics, so gene drives, too, may provoke resistance. They may do so far faster than many suspect.

None of this means that gene drives will not eventually fulfil their promise. Indeed, some researchers are developing drives intended to eliminate malaria and mosquitoes, and to create mice that cannot bear daughters, to wipe out invasive rodents. Others are trying to create white-footed mice that would be immune to infection by the bacteria that cause Lyme disease. That would prevent the ticks that eventually transmit the disease to people from becoming infected when they feed on the mice. Gene drives are also expected to play a role in the government of New Zealand’s plan to rid that country of all rats, stoats and possums by 2050. Nonetheless, the study in PLOS Genetics helps build the case that tricking evolution will be hard. To paraphrase “Jurassic Park”, life finds a way.

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