Sat, Aug 30, 2008

Nation

Mosquitoes' DNA tweaked to fight dengue, malaria

By Catherine Clabby
Raleigh News & Observer
Tucson, Arizona | Published: 12.17.2006
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 know they may court controversy. Genetically modified crops such as soybeans, corn and cotton have become common in the U.S., 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, a North Carolina State University insect expert.
Dengue fever is first focus
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 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, flulike 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.
"If you can do this with dengue, you can envision doing it with malaria," Gould said.
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.
"Things keep bearing fruit"
A breakthrough this year at Colorado State University might 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 lab 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 strategy is to piggyback onto so-called selfish genes — unusual stretches of DNA that perform no duties other than tending to their own survival.
A customized release plan will be needed. And it will likely carry a cost. Organisms absorbing altered DNA often take a fitness hit, meaning an altered mosquito may fly slower or be less successful finding a mate.
Computing power, higher math
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.
"We want to determine what's the most efficient way to use the fewest mosquitoes to get this done," Gould said.