LAUSR

I n the small city of Terni in central Italy, researchers are putting the final touches on what could be the world's most sophisticated mosquito cages. The enclosures, each occupying 150 cubic metres, simulate the muggy habitats in which Africa's Anopheles gambiae mosquitoes thrive. By studying the insects under more-natural conditions, scientists hope to better understand how to eradicate them — and malaria — using an emerging genetic-engineering technology called gene drives. The technique can quickly disseminate genetic modifications in wild populations through an organism's offspring, prompting some activists to call for it to be shelved. Yet gene drives might not be as effective as activists think. Recent research has identified a major hurdle to using them to eliminate diseases and vanquish invasive pests: evolution. Organisms altered by gene drives, including mosquitoes, have shown promise in proof-of-concept laboratory experiments. But wild populations will almost certainly develop resistance to the modifications. Researchers have begun identifying how this occurs so that they can address the problem. Gene drives thwart the rules of inheritance in sexually reproducing organisms. Normally, offspring have a 50:50 chance of inheriting a gene from their parents. Gene drives alter those odds, preferentially passing on one version to an organism's offspring until, in theory, an entire population bears that gene. Such 'selfish' genetic elements occur naturally in mice, beetles and many other organisms, and researchers have had modest success with hijacking them to battle pests. But interest in gene drives has surged with the advent of CRISPR–Cas9 gene editing, which can be used to copy a mutation from one chromosome into another. In late 2015, researchers reported a CRISPR gene drive that caused an infertility mutation in female mosquitoes to be passed on to all their offspring 1. Lab experiments showed that the mutation increased in frequency as expected over several generations, but resistance to the gene drive also emerged, preventing some mosquitoes from inheriting the modified genome. Just as antibiotics enable the rise of drug-resistant bacteria, population-suppressing gene drives create the ideal conditions for resistant organisms to flourish. One source of this resistance is the CRISPR system itself, which uses an enzyme to cut a specific DNA sequence and insert whatever genetic code a researcher wants. Occasionally, however, cells sew the incision back together after adding or deleting random DNA letters. This can result in a sequence that the CRISPR gene-drive system no longer recognizes, halting the spread …