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In the laboratory, fighting malaria with transgenic mosquitoes


In a significant step toward achieving a mosquito-based strategy for controlling malaria, scientists have given mosquitoes a gene that makes them poor transmitters of the malaria parasite. In the study genetically modified mosquitoes were 80 percent less effective at spreading malaria than normal mosquitoes.

Female Anopheles gambiae mosquito feeding. Malaria vector, parasite.

Marcelo Jacobs-Lorena, of Case Western Reserve University in Cleveland, Ohio, and colleagues created the transgenic mosquitoes using insects that spread a mouse form of malaria. Whether the strategy, tested under laboratory conditions, can be applied to the problem of controlling malaria in an infected region of the world remains to be seen, but the new study takes the field closer to exploring that possibility.

The new study demonstrates the "feasibility of generating populations of transgenic mosquitoes that have diminished potential to carry the malaria parasite," write the authors of a News and Views article accompanying the findings in Nature. The authors are Gareth J. Lycett and Fotis C. Kafatos of the European Molecular Biology Laboratory in Heidelberg, Germany.

During its life cycle in the mosquito, the malaria parasite Plasmodium falciparum migrates from the insect's gut to the salivary glands. The researchers inserted a synthetic gene that interferes with this migration. Specifically, the gene encodes a peptide that prevents the parasite from traversing the insect gut.

The gene has a regulatory element that drives its expression at the appropriate time and location in the mosquito; and the gene does not negatively affect the insect's health or its ability to pass the gene to offspring.

However, the single-gene strategy used in the study did not block the parasite's development completely, and resistant forms of the parasite might appear over time. A multi-gene strategy is more likely to inhibit the parasite completely.

In the coming months researchers are likely to have access to the annotated genomes of all three organisms involved in transmitting malaria (humans, parasites, and mosquitoes). This should speed the discovery of additional genes that can be used to modify mosquitoes.

The possible consequences of releasing populations of transgenic mosquitoes into the natural environment are among the important unknowns about the transgenic strategy. Researchers are likely to take such issues very seriously in light of the questions and misconceptions about genetically modified organisms in general.

Detection of AgCP[SM1]4 transgenic mosquitoes by transformation marker-mediated fluorescence. Top, a wild-type (non-transgenic) larva (middle) flanked by transgenic larvae viewed from the dorsal (top) or ventral (bottom) sides. Note green fluorescence of the ventral nerve cord in the latter, which is similar to marker-mediated fluorescence in Drosophila. Bottom, the head of a wild-type (left) and a transgenic (right) mosquito. The entire eye expresses GFP but which facets fluoresce depends on the angle of the incident light.

The mosquito-research community is strongly against carrying out premature experiments in the field, according to Lycett and Kafatos. They say that stringent laboratory experiments and long-term studies are widely believed to be necessary before "fully contained field trials" are undertaken. Furthermore, the community believes that "that transformed mosquitoes should meet the requirement of a 'significant probability' of reducing malaria prevalence before being released."

Jacobs-Lorena agrees with the consensus and says the new research is "a first step in the right direction." And even if all the remaining problems are resolved and the approach can be implemented, he says, the genetic modification of mosquitoes is no magic bullet.

"The solution to eradicating malaria," says Jacobs-Lorena, "will come only if we take a multi-pronged approach that includes drugs, insecticides, genetically modified mosquitoes, and hopefully vaccines."

See related GNN article
»Genetic mutation protects against malaria

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Ito, J. et al. Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417, 452-455 (May 23, 2002).
Lycett, G.J. & Kafatos, F.C. Anti-malarial mosquitoes? Nature 417, 387-388 (May 23, 2002).

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