In the history of the world, few weapons have been more destructive than a tiny mosquito bearing a microscopic dose of malaria.
The disease is one of Earth’s oldest and deadliest. It may have infected the dinosaurs. It’s been found in the mummified remains of ancient Egyptians. It’s thought to have killed Genghis Khan. One Nobel Prize-winning scientist even went so far as to suggest that malaria may be responsible for half of all human deaths, ever.
And despite our fiercest efforts at treatment and eradication — bed nets, quinine pills, pesticides, vaccines — the illness persists in killing us, to the tune of roughly half a million deaths per year.
So scientists are trying a different tactic: Instead of treating the humans, why not treat the mosquitoes?
On Monday, researchers from the University of California’s Irvine and San Diego campuses reported in the Proceedings of the National Academy of Sciences that they’ve bred a strain of mutant bugs that could all but eliminate malaria from the world’s mosquito population.
The breakthrough relies on a controversial new gene-editing technique called CRISPR-Cas9, a sort of molecular cut-and-paste that allows scientists to snip out segments of a creature’s DNA and insert new ones. With CRISPR, the California researchers added a set of genes conferring malaria resistance to their mutant mosquitoes, as well as a powerful tool called a “gene drive” that guarantees that all of the mosquitoes’ descendants would inherit their resistance.
“Gene drives” work by manipulating the laws of genetics so that the desired genes are copied onto both of an offspring’s chromosomes when a mutant mates with a wild mosquito. Ordinarily, offspring get just half their traits from each parent — but with the mutant inserting its DNA into both chromosomes, mosquitoes with the gene drive were able to pass on the resistance to 99.5 percent of their offspring, the researchers say.
According to the New York Times, the gene drive has the potential to spread malaria resistance throughout a wild population in a matter of just 10 mosquito generations, or a single summer.
Kevin Esvelt, an evolutionary engineer at Harvard University who studies the technique in yeast and wasn’t involved in the mosquito study, called the research a “major advance.”
“This work suggests that we’re a hop, skip and jump away from actual gene drive candidates for eventual release,” he told the Associated Press,
For now, the mutant mosquitoes are being kept in a highly secure lab behind a series of locked doors. That’s because, alluring though the promise of eradicating malaria might be, neither science nor society has quite reached a consensus about when or how creatures with manipulated DNA should be released into the wild — or indeed, what will happen when they are.
“[Gene editing] is a little bit like geoengineering,” MIT researcher Feng Zhang told the New Yorker earlier this month. “Once you go down that path, it may not be so reversible.”
Zhang, a biological engineer, led the first team of researchers to employ the CRISPR-Cas9 editing technique on human cells.
The research out of California was led by UC-Irvine molecular biologist Anthony James and UC-San Diego biologists Ethan Bier and Valentino Gantz.
James specializes in engineering “anti-disease” mosquitoes, with which he hopes to halt the spread of disease without killing off the world’s bug population. For the PNAS paper, he developed a gene that spurs mosquitoes’ antibodies to attack the malaria parasite (which they acquire while biting infected humans), preventing them from passing the microbe to their offspring. He tested the new gene on the eggs of an Indian mosquito species Anopheles stephensi — that way, if the bugs somehow escaped, they’d find themselves on a foreign continent with an inhospitable climate and no one to mate.
Bier and Gantz contributed the second part of the potent anti-malaria package. The pair, which effectively introduced a gene drive into fruit flies earlier this year, teamed with James to plug the tool into A. stephensi DNA. They coupled the malaria resistance gene with one that makes mosquitoes’ eyes red, so they could measure whether the resistance gene was passed on. Nearly 100 percent of the offspring had red eyes — and, presumably, malaria resistance.
“This is a significant first step,” James said in a University of California press release. “We know the gene works. The mosquitoes we created are not the final brand, but we know this technology allows us to efficiently create large populations.”
James is a member of the National Academy of Sciences, which has convened a committee to review the ethical implication of gene editing and gene drive research. In the meantime, the scientists using CRISPR worry that an accident might undermine their technique before they have a chance to demonstrate its power.
“If anyone messes up and a gene drive gets out into the wild, there will be a huge media circus,” Esvelt told Nature earlier this month, before the release of the mosquito study. “The message will be that scientists cannot be trusted to deal with this technology, and we will be set back by years.”
In a study published last week, Esvelt and his colleagues at several Boston universities unveiled a gene drive “safeguard” that can override the initial mutation in yeast cells.
James told the New York Times that the UC researchers plan to move slowly and very carefully forward with their research.
“This is the kind of technology where the first trial has to be a success,” he said.