In malaria fight, the foe becomes a friend

In the war against malaria, public health officials have drained swamps, sprayed mosquito-killing insecticides, and doled out medication in an attempt to reduce the disease's toll.

Now, researchers are looking for ways to enlist the buzzing mosquito itself in the fight. They are experimenting to see if the creature's genes can be changed or controlled in ways that destroy the malaria parasites it carries before it can pass them on to people.

Researchers say an important step along this path has been taken by a team of scientists in Europe. They've discovered three mosquito genes that appear to govern how the insect's immune system responds - or fails to respond - to the parasite's presence.

The discovery, reported in today's edition of Science, opens the door to designing chemicals that can prevent these genes from protecting the parasite, they say. This represents "a promising avenue to decrease the prevalence of malaria," says George Christophides, a scientist at the European Molecular Biology Laboratory in Heidelberg, Germany, and a member of the research team.

The results are significant, says Marcelo Jacobs-Lorena, an infectious disease specialist at the Johns Hopkins Bloomberg School of Public Health. "The parasite, when it develops, is a foreign organism" inside the mosquito, he explains. "But there are few clues on how it defends itself against the mosquito's immune system. This is a major step forward in understanding this relationship."

The emphasis on bioengineering to fight malaria has emerged at a time when researchers say the insects and the type of parasite they carry have become increasingly resistant to drugs and insecticides.

Moreover, insecticides that do work often are improperly applied, blunting their effectiveness. Some specialists say if left to themselves, these factors in the next 20 years could double today's annual death toll of 1 million to 3 million people. Young children are said to account for many, if not most, of those fatalities.

Scientists say they cleared a significant hurdle in their path to using genetics in the fight in 2002, when research teams published the complete genetic sequences for the mosquito and the parasite held responsible for malaria. Even before the genomes were published, however, scientists had been exploring the possibility of genetically engineering mosquitoes to battle the disease.

Researchers at Case Western Reserve University, for example, reported that they had developed the first "designer" mosquito whose genetic makeup had been altered to destroy the parasite while the insect still carried it.

Yet the biochemical agent the gene triggered didn't destroy all the malaria parasites, suggesting that the parasites might evolve to resist the agent. The team also acknowledged that it would be difficult to figure out ways to introduce the gene into the mosquito population.

The Heidelberg team took another approach. They wanted to identify the genes responsible for triggering or inhibiting the mosquito's immune system. Previous work had shown that the immune system detected the parasites' presence in the insect. But somehow the parasites were "fooling" the immune system into seeing them as friendly.

First the team developed a technique that made the mosquito genes ineffective, "silencing" them. Then they injected the mosquito with a rodent parasite, a stand-in for the malaria parasite. Of the genes they silenced, three stood out.

When they silenced two of the genes, the parasites had a much tougher time developing within their "host" than when the genes were active. When the team silenced only the third gene, the parasites' development was enhanced. The effects were "pronounced," the team reports.

Much remains to be done to turn these results into practical approaches, say Janet Hemingway and Alister Craig, researchers at the Liverpool School of Tropical Medicine in Britain. Still, they hold, the results are cause for optimism.