had been trying for eight years to hijack the mosquito genome. They wanted to bypass natural selection and plug in a gene that would mushroom through the population faster than a mutation handed down by the usual process of inheritance. In the back of their minds was a way to prevent malaria by spreading a gene to knock out mosquito populations so that they cannot transmit the disease. Crisanti remembers failing over and over. But finally, in 2011, the two geneticists at Imperial College London got back the DNA results they' d been hoping for: a gene they had inserted into the mosquito genome had radiated through the population, reaching more than 85% of the insects' descendants 1. It was the first engineered 'gene drive': a genetic modification designed to spread through a population at higher-than-normal rates of inheritance. Gene drives have rapidly become a routine technology in some laboratories; scientists can now whip up a drive in months. The technique relies on the gene-editing tool CRISPR and some bits of RNA to alter or silence a specific gene, or insert a new one. In the next generation, the whole drive copies itself onto its partner chromosome so that the genome no longer has the natural version of the chosen gene, and instead has two copies of the gene drive. In this way, the change is passed on to up to 100% of offspring, rather than around 50% (see 'How gene drives work'). Since 2014, scientists have engineered CRISPR-based gene-drive systems in mosquitoes, fruit flies and fungi, and are currently developing them in mice. But that's just the beginning of the story. Questions about whether a gene drive is possible have been supplanted by other unknowns: how well they will work, how to test them and who should regulate the technology. Gene drives have been proposed as a way to reduce or eliminate insect-borne diseases, control invasive species and even reverse insecticide resistance in pests. No engineered gene drive has yet been released into the wild, but the technology could in principle be ready as soon as three years from now, says Crisanti. He collaborates with Target Malaria, a non-profit international research consortium seeking to use gene-drive mosquitoes for malaria control in Africa. On 1 July, the group released a test batch of mosquitoes-genetically engineered but not yet equipped with gene drives-in a village in Burkina Faso. Gene drives are unlike any ecological fix ever tested before, says Gene-drive technology could alter the genome of an entire species. Researchers need to answer these key questions before deploying it in the wild.
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