Better mosquito: transgenic versions spread less malaria. (This Week).

Genetic engineers have built a mosquito that's wonderfully bad at transmitting malaria in lab tests.

Transgenic versions of a mosquito species that bedevils India are only 20 percent as likely to transmit a mouse version of the disease as the untransformed mosquitoes are, says Marcelo Jacobs-Lorena of Case Western Reserve University in Cleveland. The work raises hope that people might someday deploy transgenic insects to spread antimalaria genes into the wild, Jacobs-Lorena and his colleagues say in the May 23 Nature.

"It's a demonstration of something that people have been trying to do for a long time," comments Frank Collins of University of Notre Dame in Indiana. In 1998, he and Anthony James of the University of California, Irvine paved the way by proving that mosquitoes can be genetically engineered (SN: 4/4/98, p. 213).

Malaria kills some 2.7 million people each year. Unfortunately, the parasites that cause it often develop resistance to drugs, and the mosquitoes that spread those parasites often develop resistance to insecticides.

Mosquitoes pick up the parasites by biting an infected person or other animal. As the mosquito sucks infected blood, parasites work their way through the wall of the insect's gut and form a capsule. Some 10 to 15 days later, the parasites burst loose from this so-called oocyst and pass through the insect's salivary gland walls. The next time the mosquito feeds, the parasites invade a new victim.

For clues to genes that might sabotage this process, Jacobs-Lorena's group fed Anopheles stephensi mosquitoes particles coated with various strings of amino acids and then checked to see which ones stuck to the gut lining. By selecting the stickiest combinations, the researchers narrowed their search to a compound they call SM1. It hooks to both the gut lining and the salivary gland wall. The substance also significantly reduces the number of parasites that get through the gut to form oocysts.

To develop a trigger for producing SM1 at the right time, Jacobs-Lorena found a genetic on switch for a digestive enzyme that mosquito guts secrete during a blood meal and linked it to a synthetic gene designed to produce SM1.

The researchers then inserted the genetic construct into laboratory mosquitoes. It has persisted through at least a year of generations but doesn't seem to affect the insect's lifespan or egg production, says Jacobs-Lorena. Yet transgenic mosquitoes had significantly fewer oocysts and were much less competent at spreading malaria among test mice.

Collins says many scientific hurdles remain before such transgenic mosquitoes could be put to work against malaria. For example, the sabotage genes need to be tested with human malaria instead of just the mouse version. Also, researchers need a practical way to get genes into wild mosquito populations.

Ecological questions remain too. For example, Collins says he doesn't expect antimalaria mosquitoes to be more likely to pick up and spread other diseases, but the possibility needs testing.

Andrew Spielman of the Harvard School of Public Health in Boston is even more cautious about releasing transgenic mosquitoes for disease control. "The problems are enormous," he says. Transgenic insects will have to be nurtured without undercutting pest-control measures. "You can't tell people to keep their windows open so the mosquitoes can feed on their children," he says.

Jacobs-Lorena says that transgenic approaches could supplement, not replace, drugs or other antimalaria measures. "I feel strongly this approach is not a magic bullet," he says.