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Mosquitoes May Become Our Allies

December 19, 2006

Without mosquitoes, epidemics of dengue fever and malaria could not plague this planet.

The skin-piercing insects infect one person after another while dining on a favorite meal: human blood.

Eliminating the pests appears impossible. But scientists are attempting to re-engineer them so they cannot carry disease. If they manage that, they must create enough mutants to mate with wild insects and one day to outnumber them.

Researchers chasing this dream, including an N.C. State University entomologist, know they may court controversy. Genetically modified crop plants such as soybeans and corn have become common in the United States, but an altered organism on wings would be a first.

Critics of bio-engineering, especially in Europe, view some genetic alterations as unnatural, even monstrous. People fearful of so-called Frankenfood could sound similar alarms over Frankenbugs.

But with advances in molecular biology and millions of dollars from the Bill & Melinda Gates Foundation, this quest may be within reach. And its promise is huge, the scientists say.

“We’re looking at a timeline. But this is coming,” said Fred Gould, the NCSU insect expert.

Gould is working on the project with scientists on four continents. They landed $19.7 million under a Grand Challenges in Global Health grant offered by the Gates philanthropy and a National Institutes of Health foundation. The funders selected researchers ready to collaborate rather than compete on risky research aimed at solving massive health threats in poor places.

The genetic tinkering is focused at first on dengue, a tropical virus re-emerging in Asia, Latin America and Africa. While dengue claims a fraction of the million or more victims that malaria kills annually, it strikes 50 to 100 million people each year with severe flu symptoms. Outbreaks disrupt families and communities and overburden health systems.

Dengue is a good starting point because it is transmitted almost exclusively by a single mosquito species (the smallish, striped- legged Aedes aegypti) while the malaria parasite is carried by several. Focusing the effort on just one bug simplifies the science.

To try to build a less dangerous Aedes aegypti, scientists broke a huge job into smaller chunks. First, they needed a means to make female mosquitoes immune to dengue. Only females drink blood (males prefer nectar), and only insects infected with dengue can spread it.

A breakthrough this year at Colorado State University may help. Molecular biologists there stitched laboratory-made DNA into Aedes aegypti that blocks dengue from reproducing in a bug’s gut. That stops dengue from getting into mosquito saliva, which deposits the virus into human bloodstreams.

As important, the change sticks. Bugs pass the trait to their offspring.

“Things keep bearing fruit. So far, so good,” said Anthony James, a biologist at the University of California Irvine, the lead investigator for the mosquito project.

But inserting strings of DNA into laboratory mosquitoes and spreading them in the wild are two different things.

Scientists must convince the government and people of any country they approach that mutant bugs will fight disease without risk to people or the environment, said Sujatha Byravan, president of the Council for Responsible Genetics.

Scientists are trying to harness exotic genes to help slip dengue- fighting DNA into many offspring quickly. One way: piggyback onto so- called selfish genes — unusual stretches of DNA that perform no duties other than tending to their own survival.

Whichever strategy gets picked will require a customized release plan. And it will likely carry a cost. Organisms absorbing altered DNA often take a fitness hit, meaning an altered mosquito may fly slower, weigh less or be less successful finding a mate.

Gould and his team aren’t engineering insects. They are predicting each strategy’s success at passing dengue immunity to future generations. Is it best to release many in a small place or fewer over a neighborhood?

Both jobs require a mix of high-level mathematics and big computing power. But just as important is detailed knowledge of the life cycles and mating habits of Aedes aegypti.

Dengue mosquitoes often are born, live and die in or near a home. They prefer dwellings with no running water, where they can lay eggs in containers people use for cooking, bathing and cleaning. The bugs tend to bite during the day, so mosquito netting over beds offers little protection.

Understanding the life cycles of the insects will give Gould’s group clues on how to infiltrate an entire mosquito population quickly and at a reasonable cost.

“We want to determine what’s the most efficient way to use the fewest mosquitoes to get this done,” Gould said.

Once the scientists select the best strategy, they will test their predictions — but not in the wild. Plans call for experiments in insect-safe cages surrounding mock homes to be built in sparsely populated land in southern Mexico within two years.

The mock home will copy local dwellings. Inside will be clothing, kitchen implements and furniture. Outside will be potted plants and rain barrels like the ones locals use, all potential breeding grounds.

Mexico was selected because it has experience regulating bio- engineering.




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