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TITLE:  Ecologists See Flaws in Transgenic Mosquito
SOURCE: Science, by Martin Enserink
DATE:   July 5, 2002

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MALARIA: Ecologists See Flaws in Transgenic Mosquito

WAGENINGEN, THE NETHERLANDS--If a small band of molecular biologists has 
its way, the next few years might bring field tests of "designer 
mosquitoes," genetically modified so that they are unable to transmit 
diseases such as malaria. The goal would be to replace the natural mosquito 
populations ravaging developing countries. But at a workshop here last 
week,* 20 of the world's leading mosquito ecologists said, "Not so fast." 
Although lab science might be thriving, they said, huge ecological 
questions remain--and it's time funding agencies, which have 
enthusiastically endorsed the transgenic mosquito plan, started devoting 
attention and money to answering them.

Gathering in this Dutch university town, the group outlined a sweeping 
ecological research agenda, ranging from baseline population genetics to an 
emergency plan in case the transgenic critters run amok. Many of these 
issues have been deferred or overlooked by the molecular biologists 
developing the disease-fighting mosquitoes, said meeting organizer Thomas 
Scott of the University of California, Davis.

At least five U.S. and three European research groups are working on 
transgenic mosquitoes, with support from the U.S. National Institute of 
Allergy and Infectious Diseases (NIAID), the World Health Organization 
(WHO), and the MacArthur Foundation. After a slow start, the field took off 
in 1998, boosted by new genetic engineering techniques (Science, 20 October 
2000, p. 440). As they reported in the 23 May issue of Nature, Marcelo 
Jacobs-Lorena of Case Western Reserve University in Cleveland and his 
colleagues recently inserted an extra gene into Anopheles stephensi, a 
mosquito that transmits malaria in India, that made the insects resistant 
to mouse malaria. Others are tweaking the genes of Aedes aegypti, the 
mosquito that transmits dengue.

But the ultimate target is Anopheles gambiae, the main vector of the 
deadliest malaria parasite, Plasmodium falciparum, in Africa. Researchers 
hope to make resistance genes spread through natural mosquito populations 
by hitching them to a selfish piece of DNA called a transposon or to a 
strange bacterium called Wolbachia that sweeps through insect populations 
by manipulating its host's sex life. If this works, they will have created 
golden bugs that could save millions of lives--at least in theory.

At the meeting, ecologists came up with a discouraging list of hurdles that 
could easily sink the plan. For example, will the new mosquitoes be able to 
compete for partners with their natural counterparts? (Past studies have 
shown that spending a few generations in the lab diminishes their sexual 
attractiveness.) How long would it take for a new resistance gene to 
penetrate the population, and would it be 100% effective in mosquitoes that 
carry it? (If not, the transgenic bug would barely make a dent in malaria 
incidence, suggests a model by Christophe Bo‘te and Jacob Koella of the 
Pierre and Marie Curie University in Paris.) In areas with multiple malaria 
vectors, would all the species need to be "treated"? And would P. 
falciparum develop resistance to the new genes, as it has to many drugs? Or 
could this be prevented if multiple antiparasite genes were used?

Studying many of these issues is problematic. Most researchers agreed that 
after cage experiments, some sort of pilot trial would be needed. But 
where? It must be a place from which mosquitoes can't escape. Sa› Tomˇ, one 
of a handful of islands that form a republic off the east coast of Africa, 
has been suggested, and one meeting participant floated the idea of 
creating artificial "oases" in the Sahara desert. Even more vexing are some 
of the ethical and regulatory issues. Although it's unclear who would set 
the rules, a field test would have to meet safety standards as strict as 
those for vaccine trials, said entomologist Yeya Tourˇ, malaria coordinator 
at WHO's Special Programme for Research and Training in Tropical Diseases--
or perhaps even stricter, as it would expose people who had not agreed to 

Feeling "a bit like a ham sandwich on Passover," the only molecular 
biologist at the workshop, David O'Brochta of the University of Maryland, 
College Park, admitted that he and his colleagues have given little thought 
to these issues. But that reflects a lack of expertise rather than concern, 
he said, urging ecologists to join the work.

In the past, said meeting host Willem Takken of Wageningen University, 
granting agencies have not been impressed by old-style fieldwork such as 
counting mosquitoes or studying their feeding behavior. But at least NIAID 
is now convinced that the ecologists' input is urgently needed, says Kate 
Aultman, program manager for vector biology. Some at the meeting said that 
they were uncomfortable allying themselves too closely with a research 
program that faces such major problems. But most still preferred joining it 
to trying to beat it--if only because the research might be valuable 
regardless of whether transgenic mosquitoes ever take wing.

 * "The Ecology of Transgenic Mosquitoes," Wageningen University and 
Research Centre, 26-29 June.


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