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Gene-Editing Technology Could Help Eradicate Malaria, Study Shows

A groundbreaking but controversial new gene-editing technology is accelerating a push to eradicate malaria, with scientists recently identifying two ways to block mosquitoes from transmitting the killer disease.

In a study published Monday, researchers at Imperial College London engineered genetic changes in a common breed of malaria-transmitting mosquito that could cause its population to plummet—to levels low enough to stop malaria from spreading. The work, published in Nature Biotechnology, was made public just two weeks after researchers in Southern California demonstrated how they had altered a different breed of mosquito to resist the malaria parasite and to spread the new trait through the population.

Both teams of researchers achieved their results using Crispr/Cas9, a powerful new technology that has transformed genetic engineering by allowing scientists to cut and paste genes with precision. Crispr/Cas9 can also be used to build “gene drives,” a sequence of DNA that ensures the new traits are inherited and spread quickly through populations. Normally, genes have a 50% chance of being inherited.

Scientists recently identified two ways of blocking mosquitoes from transmitting malaria. The research has implications far beyond fighting malaria. PHOTO: JAMES GATHANY/ASSOCIATED PRESS

The technology is being explored for uses from editing genes that cause human diseases such as cancer to reversing insects’ resistance to pesticide. But its potential uses, particularly for human-gene editing, have also raised serious ethical questions. Concerns about its use on humans were the subject of an international summit last week in Washington, D.C., where scientists concluded “it would be irresponsible” to make inheritable changes in the human genome until the risks are better known and society addresses the ethical issues.

“This is a remarkable advance,” Kevin Esvelt said of the new study, in which he wasn’t involved. He is an expert at Harvard University who in 2014 proposed the use of Crispr gene drives to spread genetic traits through wild populations.

“The challenge is how do we assess the possible effect, what the ecological risks might be,” he said. A gene drive that can alter an entire species “gives small groups of people the power to unilaterally alter the shared environment,” he said. “This needs to be considered very carefully.”

Suppressing a population of mosquitoes that carry a devastating disease would have clear public-health benefits, said Frank Collins, a vector biologist at the University of Notre Dame who wasn’t involved in the study. “There are public-health people who would say, if I could do it with a snap of a finger I would,” he said.

Engineered mosquitoes are years off and couldn’t eradicate malaria alone, malaria experts say. But they could be a potentially powerful and relatively inexpensive tool in a newly re-energized push to halt the disease. Malaria infected about 214 million people this year, mostly in sub-Saharan Africa, killing about 438,000, most of them young children.

“We think this has huge potential both for saving a lot of lives and for doing so in a relatively species-specific way,” said Austin Burt, an evolutionary geneticist at Imperial College and an author of the new paper. But, he said, potential ecological effects are “something that has to be looked at really closely.”

The researchers at Imperial College London used Crispr/Cas9 to alter recessive genes involved in female reproduction of the anopheles gambiae mosquito, the most common carrier of the deadliest form of malaria. They then built a gene drive that passed the trait along to as many as 99.6% of the mosquitoes’ offspring.

Females with the altered trait on just one copy of a chromosome would be fertile, but would pass on the new trait, as would males that have the trait. As the trait spread through the population, a growing number of females would inherit two copies, making them sterile. Eventually so many females would be sterilized that the targeted mosquito population would crash, falling to a level too low to transmit malaria, said Tony Nolan, a researcher at Imperial College and lead author of the paper.

If the population-suppression approach works, it would be up to African government officials and scientists whether to implement it, said Fil Randazzo, deputy director of discovery and translational sciences for the Bill & Melinda Gates Foundation, which funded the study published Monday and has projected that malaria can be eradicated between 2030 and 2040. “This becomes another tool for African governments when it’s ready, and it will be done in collaboration with African scientists,” he said.

The anopheles gambiae is not the sole source of food for any predator “as far as we know,” Dr. Burt said. In many places it’s not even the most common mosquito to bite people, he said. “At the moment anyway, we don’t think there’s likely to be much in the way of a cascading ecological effect,” he said. But, he added, “We’re always on the lookout for what could possibly go wrong.”