Attempts to control malaria — which kills about 1 million people a year — have traditionally focused on the use of drugs to treat the disease and insecticides to kill mosquitoes.
Now some scientists have devised a sneakier strategy: feed mosquitoes a genetically engineered bacterium that will kill the malaria parasite from within.
Insecticides have a major flaw, said Marcelo Jacobs-Lorena, a malaria expert at Johns Hopkins University and an author of the new study. "When insecticides are used — say, inside of houses — many of the mosquitoes in the area get killed but some will always survive. It's a perfect way to select for resistance," he said. That's because the mosquitoes most resistant to insecticides will survive and have insecticide-resistant offspring. The same problem exists for anti-malaria drugs.
As a result, Jacobs-Lorena said, mosquito populations have continued to thrive, becoming more immune every day to the poisons we expose them to.
He is taking a different, more high-tech approach.
Ten years ago, his group was the first to show that mosquitoes could be genetically engineered to produce anti-malarial proteins in their guts, rendering them incapable of harboring the parasite. The idea was that the insects would be released into the wild and spread their new genes around.
But the technical and ethical barriers to this approach have been difficult to overcome. For one thing, "unless you give the mosquitoes some kind of advantage over normal mosquitoes, they cannot establish themselves," Jacobs-Lorena said. For another, mosquitoes that carry malaria tend to only mate with each other, making it hard for the resistance gene to spread through mosquito populations.
Plus there is more than one species of mosquito that carries malaria, said Michael Riehle, an entomologist at Arizona State University who was not an author on the new study. You'd have to engineer them all, he said.
Perhaps most difficult of all, there is strong public opposition to the release of genetically modified mosquitoes.
Right now, the Food and Drug Administration is reviewing a proposal from the biotech company Oxitec, of Abingdon, England, to release genetically engineered mosquitoes in Key West, Fla. The insects would be designed to breed a lethal gene into wild mosquito populations, a strategy that is already being deployed by Oxitec in Juaziero, Brazil, to great effect.
But the plan has encountered fierce local opposition in Florida because of concerns about dangers of genetically modified organisms to people and the local ecosystem.
With this in mind, Jacobs-Lorena's team has switched its strategy: Instead of modifying mosquitoes, they are genetically engineering bacteria that naturally live in the mosquito gut. The altered bacteria produce several parasite-killing proteins, including one that inserts itself into the outer membrane of the parasite, causing it to leak its contents and die.
The new study, published July 16 in the Proceedings of the National Academy of Sciences, laid out the basic principles.
First, the researchers took advantage of mosquitoes' love for sweets, getting them to feast on cotton balls that were soaked in a mix of genetically engineered bacteria and sugar. The bacteria traveled with the sugar to the mosquito's gut, where they took up residence among the sea of microbes living there already.
Next, the scientists allowed the mosquitoes to feast on malaria-tainted blood to see whether the parasite would survive.
"It was amazing," said Jacobs-Lorena: The proportion of mosquitoes carrying the parasite dropped by 84% and overall parasite levels dropped by more than 90%.
Infectious disease expert Dr. Ravi Durvasula of the University of New Mexico said the work is promising both because of its apparent success and because it avoids some of the pitfalls of previous methods.
"It's important that they're not tinkering with the genome of the insect itself," he said; many researchers believe that people are less likely to object to genetically modified bacteria.
But there's still a long way to go before the technique can be deployed in the areas that need it most, he added. Most significantly, public health officials would have to devise a way to get the engineered bacteria into the guts of all the wild mosquitoes.
Jacobs-Lorena believes he has a winning strategy: clay pots.
His plan, hatched with collaborators in Burkina Faso in West Africa, is to stash sugar- and bacteria-soaked cotton balls in clay jars. During the day, mosquitoes like to hang out in dark, humid environments, so the clay jars attract them.
"We think that could be an effective way to introduce the bacteria into the mosquitoes," he said.
Even when the technique is perfected, the engineered bacteria will still need to go through regulatory hoops, and public health officials will need to convince wary citizens that the approach carries no risk to people or the environment, Jacobs-Lorena said.
"If we can convince people that the benefits outweigh the risks, I think we will have a chance," he said. "We're talking here about saving lives."