Countless millions of lives might be saved, and the lives of hundreds of millions transformed for the better, by the first working gene drive. The gene drive completely wiped out all the mosquitoes in small cages in less than a dozen generations.
“There were no progeny, not a single one,” says Andrea Crisanti of Imperial College London, whose team’s gene drive is based on the CRISPR gene-editing method . “It goes to extinction.”
There are 200 million cases of malaria each year and half a million deaths – mostly among children. Those who survive often have lasting physical or mental impairments. Recurring bouts of malaria can also trap families in a cycle of illness and poverty.
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“Beyond the human suffering, the economic costs are staggering,” billionaire Bill Gates, whose charitable foundation is helping fund the work, . “Used responsibly, gene editing holds the potential to save millions of lives and empower millions of people to lift themselves out of poverty. It would be a tragedy to pass up the opportunity.”
Parasitic DNA
Gene drives are pieces of “parasitic” DNA that geneticists insert into one of an organism’s chromosomes. Because chromosomes generally come in pairs, only one of which is passed from a parent to its offspring, usually an extra piece of DNA would only be inherited by half an animal’s progeny. But gene drives “copy and paste” themselves so that they are present in both chromosomes in a pair, meaning they get passed on to all offspring and that the drive spreads throughout a population.
Until now, however, all the gene drives tested in labs have stopped spreading after a few generations. The reason is that gene drives copy and paste themselves into specific target sites. If the target sequence mutates, they stop working.
To avoid this kind of resistance evolving, Crisanti’s team chose a target sequence that plays a crucial role in the development of female mosquitoes and therefore cannot mutate. Only one minor variant in this sequence is known to exist in the wild – and it doesn’t stop the gene drive working.
If the gene drive has copied and pasted itself into both copies of the target sequence inherited by a female, it blocks normal development. Instead, they develop male genitalia and are completely infertile. “They are genetically female but develop a lot of male characteristics,” says Crisanti.
Population crash
However, males carrying the gene drive, and females with just one copy, look and behave normally, meaning the gene drive can spread rapidly. Eventually all females inherit two copies and the population suddenly crashes.
Crisanti’s team found no evidence of resistance evolving in their lab tests, which involved two cages with a starting population of 600 mosquitoes each. “We are really excited about this,” he says. “We are over the moon.”
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To find out if resistance could develop in larger populations and if the drive will work in the wild, the team will now carry out tests in much bigger cages in Italy designed to mimic conditions in the tropics. The work will follow guidelines set out by the US National Academies of Sciences in 2016. Even if the Anopheles gambiae mosquitoes escape, they cannot survive in the region or interbreed with local mosquito species, Crisanti says.
The target sequence is identical in all malaria-carrying mosquitoes, so the same gene drive would be effective against all of them. However, the sequence differs in other kinds of insects, so the gene drive would not affect non-target insects even if it somehow got inside them.
Scourge of malaria
Discussions about field tests are already underway with Burkina Faso, Uganda and Mali. Any release of the gene drive in the wild would require the agreement of all the countries it might spread to.
“For a scourge such as malaria, a diplomatic agreement among all affected countries is feasible,” Kevin Esvelt of MIT, a leading gene drive researcher, told żěè¶ĚĘÓƵ recently. .
However, Esvelt is opposed to any release of this kind of gene drive for purposes other than eliminating diseases, such as for tackling invasive species. The risk of a gene drive spreading or being smuggled into other areas is too great, he warned last year.
Some environmental activists want a ban on the release of any gene drive, but when it comes to malaria many biologists think the potential benefits far outweigh any risks. Nevertheless, we must be cautious. “There is very little precedent for when science puts into the hands of humankind such a powerful tool,” says Crisanti.
Nature Biotechnology
