What's In A Species? Maybe A Cure For Malaria

Genetic analysis conducted at the University of Texas Medical Branch at Galveston (UTMB) has revealed that two populations of the mosquito Anopheles gambiae-which some scientists had speculated did not interbreed-can actually mate. The findings, which were published in the Nov. 25 issue of the Proceedings of the National Academy of Sciences, is an encouraging sign for researchers trying to find ways to genetically manipulate mosquitoes, making them incapable of carrying or transmitting the parasite that causes malaria.

Malaria afflicts between 100 million and 300 million people in the world each year, and it kills between two and three million people. It is transmitted by about 60 different kinds of mosquito. A. gambiae carries the most deadly form of malaria parasite, Plasmodium falciparum, which causes more than 95 percent of all malaria deaths. In conventional terms, A. gambiae is considered a species-that is, a group of organisms that only breeds with its own members and not with members of other species.

However, scientists studying the genetic composition of A. gambiae recently noticed something remarkable about certain populations of this mosquito. Living in the same villages-and biting the same people-are up to three groups of A. gambiae that have very different genetic profiles. One explanation for those different genetic make-ups is that the mosquitoes don't interbreed. The implication: In the ongoing process whereby organisms evolve, these three mosquito populations are on their way to becoming-or may already have become-different species.

That theory, though never directly tested, cast a cloud over a pipe dream held by a small group of scientists, including Greg Lanzaro, a medical entomologist and member of UTMB's World Health Organization Collaborating Center for Tropical Diseases. Lanzaro and about two dozen other researchers in the United States and elsewhere are busy working on separate aspects of a complicated and admittedly long-shot proposal. Following successful genetically based campaigns to wipe out other human-related scourges such as the cattle-destroying screwworm, the scientists would like to genetically engineer mosquitoes that couldn't carry or transmit malaria. Once designed, those mosquitoes could be introduced into environments where malaria-carrying mosquitoes reside, replacing the natural, more hazardous bugs with harmless ones.

Since the malaria parasite must live in and be transmitted by mosquitoes before it can cause disease in humans, the genetic approach would interrupt the normal disease cycle. The new plan would be an alternative to other malaria-control approaches, including the now-troublesome practice of using insecticides to kill malaria-carrying mosquitoes, many of which have become resistant to the pesticides. Scientists also hope the new approach will prove more successful than the long-unfruitful search for a malaria vaccine.

Taking some of the first steps toward the goal of genetic control, molecular biologists at New York and Duke universities and at the National Institutes of Health have identified at least two naturally occurring characteristics that make some mosquitoes unable to transmit malaria. They are now working to identify the genes that control those biological processes. Meanwhile, other scientists at the University of California at Irvine are having preliminary success at figuring out how to introduce chosen genes into mosquitoes, which have proven harder to manipulate than other, more engineering-friendly animals such as fruitflies and mice.

But for whole proposal to work, scientists have to find a way to get genes to move from a relatively small population of introduced mosquitoes into millions of naturally occurring bugs. For that to happen, the mosquitoes need to interbreed.

For example, three genetically distinct populations-known by the names Bamako, Mopti and Savannah-live in many West African villages, including some located along the Niger River in Mali, a country near Africa's northwestern coast.

"If the three populations were separate species," says Lanzaro, "and you introduced a gene into one of them, then the gene would only be passed to, say, a third of the mosquitoes in that area. The rest of the mosquitoes, being unable to mix their genes through breeding, would still be genetically capable of transmitting the disease."

By collecting female mosquitoes in several Malian villages and analyzing their genetic make-up, Lanzaro and his colleagues at the Malaria Research and Training Center in Mali have determined that genes appear to move between two of the three existing populations, Bamako and Mopti.

"Those were the two populations that many scientists said didn't interbreed at all," Lanzaro says. "But we're seeing a pattern that suggests there's lots of mating going on."

Those results suggest that, instead of being completely different species, the three populations could be different races of A. gambiae. If that's true, it probably wouldn't matter which mosquito race scientists use to introduce malaria-resistance genes. What matters more, Lanzaro speculates, is where on the insects' chromosomes the scientists place whatever genes they eventually decide to use.

"We're laying the groundwork for the final stages of this plan," says Lanzaro. "It may take us 20 years to get there, but if the plan works, millions of people could be free from a scourge that has plagued human beings for centuries."