After years of struggling with a variety of strategies to prevent or reduce deadly mosquito-borne diseases, scientists are now exploring the feasibility of using genetically modified disease-resistant mosquitoes to breed with and largely replace their disease-causing counterparts in the wild.

If this new strategy is to succeed, however, the very basic ecology and population biology of mosquitoes needs to be better understood, according to an international group of mosquito researchers who gathered recently in The Netherlands.

Thomas W. Scott, a medical entomologist at the University of California, Davis, and colleagues report the group's recommendations in the Oct. 4 issue of the journal Science.

Many infectious diseases are carried by mosquitoes to humans. The mosquito bites and sucks blood from an infected person then moves on to do the same to a different person, effectively moving viral particles or parasites through a community via blood. Among the mosquito-borne diseases of particular concern are malaria and dengue fever.

It has been suggested that laboratory-bred mosquitoes, genetically modified to be resistant to specific diseases, could be released into the wild. These modified mosquitoes would breed with their wild relatives and introduce into the wild population the genes for disease resistance. Eventually the number of disease-carrying, non-resistant mosquitoes would be reduced to a level that would significantly curtail human infection.

"Before this approach will be considered safe and effective we need to have a much better understanding of mosquito ecology, such as mating patterns and reproductive behavior," said Scott, director of the UC Davis Arbovirus Research Unit. An expert in the ecology and evolution of mosquitoes and how they transmit diseases, Scott recently helped confirm California's first human case of West Nile virus.

One of the main areas that needs to be addressed, Scott and colleagues note, is how transgenes -- genes inserted into genetically modified mosquitoes -- will move into the wild mosquito population. This process will be affected by mating patterns of the wild mosquitoes, the size of the targeted wild-mosquito population and the fitness of the genetically engineered mosquitoes reared in the laboratory.

It is important that the genes introduced into genetically modified mosquitoes not detract from the overall fitness of the mosquitoes -- that is their ability to survive, reproduce and function normally. If the transgenes reduce mosquito fitness, those introduced genes might eventually be eliminated because the mosquitoes carrying them would not thrive as well as the wild mosquitoes.

"It's crucial that we know what the evolutionary costs of genetic manipulation are and how those costs will shape our plans for blocking disease transmission," Scott said.

He and colleagues stress that future research needs to examine the possibility that mosquito-borne parasites, such as the Plasmodium parasite that causes malaria, may evolve resistance to the introduced genes just as they have become resistant to certain drugs. Scientists need to be able to predict to what extent parasites will develop resistance to genetically engineered resistance and whether resistance will also impact the effectiveness of vaccines and drugs now used to fight malaria and other mosquito-borne diseases.

Research also needs to explore how reduction of disease-causing mosquitoes in wild populations will affect patterns of human infection. The goal of using GM mosquitoes would be to reduce human infection by drastically cutting the numbers of disease-causing mosquitoes in the wild. However previous research with malaria indicates that the severity of disease may actually increase when the overall number of human infections decreases because transmission slows down and consequently more people are infected for the first time as adults. For malaria and dengue, first infections in adults cause more severe illness than in children.

Scott and colleagues recommend that future research also examine the effect on human health if use of currently applied insecticides is terminated after the genetically modified mosquitoes are released so that beneficial, resistant mosquitoes are not killed.

They suggest that mathematical models be developed to predict the outcomes of various programs involving the introduction of genetically modified mosquitoes.

In addition to the scientific studies, the authors of the article recommend that researchers address ethical, legal and social issues related to the use of genetically modified mosquitoes to thwart mosquito-borne diseases.

They indicate that successful deployment of genetically modified mosquitoes will require adequate facilities, staffing, and funding. Semi-field studies with genetically modified mosquitoes might be conducted in large outdoor cages followed by releases on islands or other ecologically isolated areas. Such areas should have mosquito populations that have been well characterized in terms of their genetic and ecological make-up.

This paper is an overview of presentations at The Ecology of Genetically Modified Mosquitoes meeting held in June in Wageningen, The Netherlands.