Transgenic Mosquitoes Might Slow Malaria

BALTIMORE, March 21 -- Genetically modified mosquitoes with glowing green eyes could turn the tables one day on malaria, according to researchers here.

In laboratory experiments, mosquitoes modified so that the malaria parasite can't develop in the insect gut lived longer and produced more offspring than wild-type mosquitoes, said Marcelo Jacobs-Lorena, Ph.D., of the Malaria Research Institute at Johns Hopkins University here.

The implication is that the modified mosquitoes might be able to out compete their normal cousins and slow the spread of malaria, Dr. Jacobs-Lorena and colleagues reported in the March 27 issue of the Proceedings of the National Academy of Sciences.

"To our knowledge, no one has previously reported a demonstration that transgenic mosquitoes can exhibit a fitness advantage over nontransgenics," Dr. Jacobs-Lorena and colleagues said.

When modified mosquitoes and wild-type insects were allowed to feed on mice infected with Plasmodium berghei, the transgenic insects became 70% of the population after nine generations.

The researchers were able to count the transgenic insects because part of the genetic manipulation caused their eyes to glow green under fluorescent light.

The transgenic insects express a peptide, SM1, that prevents invasion of the salivary gland and midgut epithelia by P. berghei, in essence preventing the parasite from developing.

In other experiments, the researchers pulled a switch halfway through.

They began by allowing the insects to feed on mice infected with a strain of P. berghei that is capable of producing gametocytes. Then they switched the insect the mice infected with a parasite that can't produce gametocytes - and therefore can't develop normally.

The frequency of the transgenic insects stopped increasing after the switch, showing that it was parasite development in the insect that affected fitness, the researchers said.

The transgenic insects were less likely to die after feeding than were the wild-type mosquitoes. The cumulative mortality six days after feeding was 38.5% among the transgenic insects, compared with 51.4% of the wild-type, a difference that was significant at P=0.027.

When the insects were fed on mice infected with a parasite incapable of producing gametocytes, there was no difference in mortality, Dr. Jacobs-Lorena and colleagues reported.

The transgenic mosquitoes also produced more eggs than did the wild-type insects, they said, but again the difference disappeared when they were fed on mice infected with a parasite incapable of producing gametocytes.

The researchers cautioned that the findings were made in a model system, and may not translate quickly or immediately to the outside world.

Among other things, Dr. Jacobs-Lorena and colleagues noted, the prevalence of infected mosquitoes in the wild is much lower than in these experiments, so that the spread of transgenic insects would be slower.

Moreover, the parasite used in the experiments was P. berghei, not P. falciparum, which infects humans. The two parasites are similar, but not identical.