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How An Altered Strand Of DNA Can Cause Malaria-Spreading Mosquitoes To Self-Destruct

For the first time, scientists have shown that a new kind of genetic engineering can crash populations of malaria-spreading mosquitoes.

In the landmark study, published Wednesday in the journal Nature Communications, researchers placed the genetically modified mosquitoes in a special laboratory that simulated the conditions in sub-Saharan Africa, where they spread the deadly disease.

The male mosquitoes were engineered with a sequence of DNA known as a "gene drive" that can rapidly transmit a deleterious mutation that essentially wipes out populations of the insects.

The goal is to create a powerful new tool to fight malaria, which remains one of the world's most terrible scourges.

"Our study is the first [that] could show that gene-drive technology works under ecologically challenging conditions," says Ruth Muller, an entomologist who led the research at PoloGGB, a high-security lab in Terni, Italy. "This is the big breakthrough that we made with our study."

This research is supported by the Bill and Melinda Gates Foundation, which is a sponsor of NPR and this blog.

Many years of additional research will be needed to prove the approach works and the mosquitoes would be safe to release into the wild. The project would also require regulatory approval and agreement by local residents in areas where those mosquitoes live, mostly in sub-Saharan Africa and parts of Asia.

Despite years of efforts, malaria remains a major health problem. The mosquito-borne parasitic disease sickens more than 200 million people every year and kills more than 400,000, many of whom are children.

So Muller and her colleagues decided to use CRISPR, a technique that enables scientists to easily make very precise changes in DNA to genetically modify the Anopheles gambiae species of mosquito, which spreads malaria in sub-Saharan Africa.

The modification consisted of a mutation in a gene known as "doublesex," which female mosquitoes need for normal development. The mutation deforms their mouths, making them unable to bite and spread the parasite. It also deforms their reproductive organs, rendering them unable to lay eggs.

The mutation is combined with a gene drive, "effectively a selfish type of genetic element that spreads itself in the mosquito population," says Tony Nolan of the Liverpool School of Tropical Medicine, who helped develop and test the mosquitoes.

Because of fears of disrupting the delicate balance of ecosystems, the researchers have taken extraordinary steps to prevent the insects from escaping. The scientists first tested the mosquitoes in a high-security basement lab in London, where the mosquitoes destroyed unmodified mosquitoes in small cages.

To try to safely test the mosquitoes under more natural conditions, the researchers built a special high-security lab in Italy designed to keep their gene-drive mosquitoes from escaping. For example, anyone entering the most secure part of the lab had to pass through a special chamber that would prevent any mosquitoes from exiting. The lab was purposefully located far from Africa in case, somehow, any mosquitoes managed to get out.

The researchers then released dozens of the gene-drive mosquitoes into special large cages containing hundreds of natural mosquitoes. Unlike the small cages in London, the cages in Italy were much larger and mimicked the environment in sub-Saharan Africa, including temperature, humidity and even the timing of sunrise and sunset.

The gene-drive mosquitoes decimated the natural mosquito populations in less than a year, the study authors reported.

Other researchers are welcoming the advance.

"It is a step in the right direction," says Anthony James, a professor of microbiology and genetics at the University of California, Irvine, who is pursuing similar research. "It's extremely important."

"In my opinion, the use of gene-drive mosquitoes are going to be effective against the spread of malaria or other vector-borne diseases," says Jeantine Lunshof, a bioethicist at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

"I think the benefits of it are so great and I have not found convincing arguments that this would have considerable detrimental effects," she says.

Others are highly skeptical and say the technology is too dangerous.

"The idea of gene-drive mosquitoes is something that is very disturbing to me and to many of the people I speak to," says Nnimmo Bassey, who heads the Health of Mother Earth Foundation in Nigeria, an environmental advocacy group. "It has the possibility of disrupting the balance in our ecosystems" in ways that can't be predicted.

"This experiment is another reminder that there isn't a safe or ethical way to experiment with gene drives," wrote Dana Perls of the environmental group Friends of the Earth in an email to NPR. "Until there are robust, international, precautionary regulations and oversight, we need to hit the pause button on gene-drive organisms."

Copyright 2021 NPR. To see more, visit https://www.npr.org.

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