Colorful gene marks mosquito manipulation.

Vampires may star in movies and television shows, but mosquitoes are the deadliest bloodsuckers around. While feeding, mosquitoes infect millions of people with the microorganisms that cause killer diseases such as dengue and yellow fevers and malaria.

Eradicating these insects has proved impractical, and vaccines for the illnesses are unavailable, so some researchers are exploring another option: genetically engineering mosquitoes so they can no longer pass on the pathogens.

Investigators have now taken a major step toward that goal by showing that they can add to one mosquito species a working gene that is inherited by future generations.

The method used to transform the insects, developed in concert by research groups led by Anthony A. James of the University of California, Irvine and Frank H. Collins of Notre Dame University in South Bend, Ind., appears in the March 31 Proceedings of the National Academy of Sciences.

In these initial studies, the added gene merely provides a visible marker--a change in eye color--that registers the technique's success. The scientists envision eventually inserting genes that would make mosquitoes unable to transmit viruses or the parasite that causes malaria.

"This achievement opens a wide vista of possibilities of introducing and testing foreign DNA sequences in the mosquito germ line for both basic research and the development of a wide array of biological control methods," note Margaret G. Kidwell and Alice R. Wattam, both of the University of Arizona in Tucson, in an accompanying commentary.

The investigators worked with Aedes aegypti, a species that spreads the viruses causing dengue and yellow fevers. A natural mutant strain, which has white eyes instead of dark purple ones, offered a clear test of their manipulations. If they could alter the mutant's eye color, say by inserting the fruit fly gene that gives those flies' eyes a reddish tint, the investigators would have visible proof of their ability to add genes.

To deliver the genetic cargo, they turned to transposable elements, unusual DNA sequences that can cut themselves out of chromosomes and insert themselves elsewhere in DNA, even in a different chromosome. Collins' group spliced the gene for eye color into two different transposable elements, one from fruit flies and one from house flies, and James' team injected copies of this DNA construct into Aedes aegypti embryos.

Several of the manipulated insects were born with a reddish eye color uncharacteristic of the species. Moreover, in some cases, this coloring has persisted for 10 generations, attesting to the added gene's stable integration into the mosquito genome.

Other scientists have shown that they can infect mosquitoes with viruses engineered to carry genes that thwart human pathogens (SN: 5/11/96, p. 295). That protection isn't heritable, however, so investigators are planning to take such protective genes and use transposable elements to install them in the mosquito genome.

By introducing resistant insects into nature, the scientists hope ultimately to spread the protective genes to most mosquitoes in the wild. To combat malaria, researchers must duplicate their genetic engineering feat in Anopheles gambiae, the mosquito primarily responsible for spreading that disease.