November 12, 2010

Genetically-altered Mosquitoes Take Part In Dengue Trial

British scientists have created genetically modified sterile mosquitoes in an experiment to kill off others in their species, and researchers are hopeful that early field trials could help to stave off the rapid spread of dengue fever.

This is the first time genetically altered mosquitoes have been set loose in the wild, after years of lab experiments and calculations. But while scientists believe the trial could lead to a breakthrough in halting the disease, critics argue that mutant mosquitoes could possibly wreak havoc on the environment.

Dengue fever, a potentially life-threatening febrile disease that occurs in the tropics, is spread through the bite of infected female Aedes aegypti mosquitoes. More than 2.5 billion people are at risk and the World Health Organization estimates there are at least 50 million cases every year. There is no treatment or vaccine.

"This test in the Cayman Islands could be a big step forward," Andrew Read, a professor of biology and entomology at Pennsylvania State University, who was not involved in the project, told the Associated Press (AP). "Anything that could selectively remove insects transmitting really nasty diseases would be very helpful."

Scientists from Oxitec, a company that uses modern biotechnology to develop insect strains that are sterile and that can be used to control pests of both public health and agriculture, ran a small trial with the Mosquito Research and Control Unit (MRCU) in the Cayman Islands in the Caribbean. They found that releasing the genetically altered insects into a small 40-acre area three times a week from May to October managed to wipe out 80 percent of the species in just six months.

Luke Alphey, Oxitec's chief scientist and co-founder, said with such a small area, it would have been very difficult to detect a drop in dengue cases. But their modeling estimates suggested an 80 percent reduction in mosquitoes should result in fewer dengue infections.

"The idea is based on releasing sterile males who will go out and mate with wild females," Alphey told Reuters. "One of the main advantages is that the males actively look for the females -- that's what they are programmed to do."

Larvae are produced but most die before they hatch and the rest survive only a short time as mosquitoes.

While there currently is no treatment for dengue fever, French drugmaker Sanofi-Aventis is one of various groups seeking to develop vaccines. It is testing its candidate in late stage clinical trials, but experts say it could be many years before a vaccine is on the market.

Alphey's team bred male Aedes aegypti mosquitoes which can attract and mate with females but are genetically engineered to die if they do not feed on a certain antidote, in this case an antibiotic called tetracycline.

"We put a segment of DNA into the mosquito which means it will die unless it gets the antidote," Alphey told Reuters at a briefing in London on Thursday.

"By giving them tetracycline in the lab, we can keep them alive and breed large numbers of them, but when we release the males into the environment and they mate with wild females, all the offspring inherit a copy of the gene that kills them if they don't get the antidote...so they die," he said.

Angela Harris of the Cayman MRCU, told Reuters that she was very encouraged by the results of the trial. "This kind of technology really has a place for reducing dengue and having an impact on human health," she said.

"One of dengue's main problems is that there's no cure, there's no vaccine and there are no drugs you can take to avoid it or get better from it. So the only control you can really come by ... is killing the mosquitoes and making sure they're not there to transmit the virus in the first place," she added.

But some experts warn that the genetically modified mosquitoes could become an environmental nightmare.

"If we remove an insect like the mosquito from the ecosystem, we don't know what the impact will be," Pete Riley, campaign director of GM Freeze, a British non-profit group that opposes genetic modification, told AP.

Mosquito larvae might be food for other animal species, which could starve if the larvae disappear, said Riley. Or taking out adult mosquito predators might open up a slot for other insect species to slide in, potentially introducing new diseases.

The track record of humans interfering with natural ecosystems has been rather sketchy, he said. In the past, such interventions have led to overpopulation of species including rabbits and deer. "Nature often does just fine controlling its problems until we come along and blunder into it," said Riley.

Alphey said the genetically modified mosquitoes cannot permanently change the ecosystem because they only live for a single generation. But to halt dengue in endemic areas like Asia and South America, billions of the modified mosquitoes would likely be needed to choke off their wild counterparts.

Yeya Toure, who leads the World Health Organization's team on Innovative Vector Control Interventions, told AP that the Cayman Islands trial was promising and said it's worth continuing the genetic modification experiments.

He said genetically altered mosquitoes aren't meant to replace existing applications such as insecticides, but to compensate for their limitations, especially when mosquitoes develop resistances.

Alphey said his Oxford-based firm is talking with officials from various countries, including Malaysia, Brazil and Panama about conducting larger trials in those countries to stifle dengue fever.

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