Not So Wimpy: Antimalarial mosquito has an edge in tests

For the first time, a mosquito strain engineered to resist malaria has beaten regular mosquitoes in a lab test of overall fitness.

The finding offers encouragement to scientists working to fight human malaria by bioengineering mosquitoes that don’t readily spread the disease. Researchers have been uncertain whether a genetically engineered, or transgenic, mosquito could survive in the real world well enough to pass along its genes for disease resistance.

The new test doesn’t show that resistance genes will spread in the wild, but the results are a “proof of principle,” says Jason L. Rasgon of Johns Hopkins University in Baltimore.

Since 1998, when researchers first manipulated the genes of a mosquito, several teams have inserted genes that make lab insects less hospitable to malaria parasites. However, tests of such disease-resistant strains of two mosquito species showed that they didn’t survive and reproduce as well as wild strains did. Then in 2004, Marcelo Jacobs-Lorena, now also at Johns Hopkins, reported that mosquitoes in his group’s malaria-resistant strain were at least as fit as regular mosquitoes when both strains fed on blood from healthy mice.

For the new study, Jacobs-Lorena, Rasgon, and their colleagues used the same strain of mosquito species Anopheles stephensi. In India, the species is a significant transmitter of human malaria.

Jacobs-Lorena and his colleagues had already inserted into the mosquito a gene for making the small peptide SM1 in the gut (SN: 5/25/02, p. 324: Available to subscribers at Better Mosquito: Transgenic versions spread less malaria). The peptide deters the rodent-malaria parasite from forming the pouch where it produces a new family of infective parasites.

The Johns Hopkins team filled cages with equal numbers of wild mosquitoes and ones carrying the gene for SM1. All the insects fed on mice teeming with malarial parasites. After the mosquitoes reproduced, the researchers randomly selected offspring from the cages to start a new generation. By the ninth generation, the populations had shifted to 70 percent transgenic mosquitoes and only 30 percent wild ones.

In a second experiment, the researchers found evidence that the malaria parasite weakens a mosquito when it settles into its gut, the team reports in the March 27 Proceedings of the National Academy of Sciences.

Mosquitoes in the wild wouldn’t get a steady diet of infected blood, so the altered insects wouldn’t win out against the others, Rasgon says.

Still, the result “has undermined an assumption that was floating around in this field,” says insect molecular geneticist David O’Brochta of the University of Maryland Biotechnology Institute in Shady Grove. “We thought putting transgenes in was going to be a drag [on the mosquitoes],” he says.

The result “highlights once more the need to assess the capabilities of the genetically modified mosquitoes under different conditions,” adds Yeya Touré, who coordinates antimalarial research for a program of the World Health Organization, which is based in Geneva. It reports that more than a million people die each year from malaria.