FEATURE ARTICLE
Genetic Strategies for Controlling Mosquito-Borne Diseases
Engineered genes that block the transmission of malaria and dengue can hitch a ride on selfish DNA and spread into wild populations
Fred Gould, Krisztian Magori, Yunxin Huang
Social Context and Risk
When we mention genetically engineered mosquitoes in conversations with our friends and colleagues, a sizeable fraction of them seem to cringe. Just the idea of such an insect scares them. Given the public discomfort with genetically engineered crops (which cannot perpetuate themselves), we expect to meet significant anxiety when people realize that our goal is to build a mosquito that outcompetes the natives.
The Pew Charitable Fund and other groups have begun to examine the social, ecological and public-health issues that would accompany the release of an engineered mosquito. Scientists and health agencies need to educate the public about the true biological properties of genetically modified organisms. Research and regulation in this area will need to be wide open to public scrutiny. The prospective release of these mosquitoes in developing countries presents unique challenges as well. We hope that people will be more likely to accept this type of genetic engineering because of the public benefit and the fact that nonprofit groups are in charge, but to earn this endorsement, scientists need to talk about the real risk involved. The nature of that risk depends in part on the type of genetic-drive system and the disease target. For example, an engineered transposon would be unlikely to stop at national borders, so a release in one country would eventually spill into bordering countries and beyond. Alternatively, if the anti-pathogen gene were driven by an underdominance construct, then the spread would probably be much more local. (Transgenic mosquitoes are unlikely to reach high enough numbers in new areas to replace the local strain.)
Too much success could also cause trouble in the future. For example, if all the mosquitoes in a certain region were dengue-free, then a growing fraction of the population would never have been exposed to the virus. If dengue then evolved so that it could hitch a ride even on a transgene-carrying mosquito, then the human population could be vulnerable to an epidemic.
Fortunately, the increase in pesticide resistance (which would have a similar effect) has not caused such rebound epidemics, but epidemiologists do not have enough information to dismiss the possibility of future breakouts. The release of engineered mosquitoes would have to include careful monitoring and contingency plans—insecticides, different transgenic strains or vaccines (if available)—for dealing with the risk of newly evolved strains of malaria or dengue. Geneticists are already looking for ways to engineer mosquitoes that have multiple means of blocking the pathogen. (Physicians prescribe a "cocktail" of drugs to combat the AIDS virus for the same reason: A virus that mutates to overcome one drug still gets knocked down by others, preventing the spread of the drug-resistance mutation.) Given the evolutionary plasticity of microbes there is no room for complacency.
The uncertainty, effort and expense have led some scientists on the front lines in the fight against mosquito-borne diseases to oppose this line of high-tech research. Current disease-control programs are severely underfunded, and they worry that the excitement over genetic engineering will pull more money away from proven technologies such as bed nets and pesticides. This critique is valid, and funding agencies need to preserve a balanced approach. High-tech projects should not grow at the expense of these other initiatives.
You can hear both optimism and frustration at meetings where entomologists get together to talk over genetic control strategies. Scientists in this field have made great progress in the past 10 years, but major technical and social hurdles remain. In the end there will be poetic justice if biologists are able to use selfish DNA to serve the altruistic goal of improving world health.
Bibliography
- Bello, B., D. Resendez-Perez and W. J. Gehring. 1998. Spatial and temporal targeting of gene expression in Drosophila by means of a tetracycline-dependent transactivator system. Development 125:2193-2202.
- Curtis, C. F. 2000. Infectious disease: The case for deemphasizing genomics in malaria control. Science 290:1508.
- Franz, A. W. E., I. Sanchez-Vargas, Z. N. Adelman, C. D. Blair, B. J. Beaty, A. A. James and K. E. Olson. 2006. Engineering RNA interference-based resistance to dengue virus type 2 in genetically-modified Aedes aegypti. Proceedings of the National Academy of Sciences of the U.S.A. 103:4198-4203.
- Gong, P., M. J. Epton, G. L. Fu, S. Scaife, A. Hiscox, K. C. Condon, G. C. Condon, N. I. Morrison, D. W. Kelly, T. Dafa'alla, P. G. Coleman and L. Alphey. 2005. A dominant lethal genetic system for autocidal control of the Mediterranean fruitfly. Nature Biotechnology 23:453-456.
- Gould, F., and P. Schliekelman. 2004. Population genetics of autocidal control and strain replacement. Annual Review of Entomology 49:193-217.
- Ito, J., A. Ghosh, L. A. Moreira, E. A. Wimmer and M. Jacobs-Lorena. 2002. Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417:452-455.
- James, A. A. 2005. Gene drive systems in mosquitoes: Rules of the road. Trends in Parasitology 21:64-67.
- Magori, K., and F. Gould. 2006. Genetically engineered underdominance for manipulation of pest populations: A determinisitic model. Genetics. (Published online ahead of print January 16. doi:10.1534/genetics.105.051789.)
- Medvedev, Z. A. 1969. The Rise and Fall of T. D. Lysenko. translated by I. M. Lerner. New York: Columbia University Press.
- Scott, T. W., W. Takken, B. G. J. Knols and C. Boete. 2002. The ecology of genetically modified mosquitoes. Science 298:117-119.
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