Genetically modified (GM) mosquitoes could soon be released into the wild in an attempt to combat malaria. Scientists at Imperial College London, who created the GM insects, say they could wipe out natural mosquito populations and save thousands of lives in malaria-stricken regions.
Led by Andrea Crisanti, the team added a gene that makes the testicles of the male mosquitoes fluorescent, allowing the scientists to distinguish and easily separate them from females. The plan is to breed, sterilize and release millions of these male insects so they mate with wild females but produce no offspring, eradicating insects in the target region within weeks.
Specific
Crisanti said: "Our mosquitoes are nearly ready for testing in the wild. This is a technology that works and could make a real difference. The beauty is that it's very specific. Unlike insecticides, sterile males target only the species you want to attack."
Mosquitoes that spread malaria have long been a target for sterile-male technology, which has been used to eradicate the screwworm fly from the US, Mexico and Central America.
The International Atomic Energy Agency has been using its radiation technology to support health projects, and wants to release sterile mosquitoes to tackle malaria in northern Sudan and on Reunion island in the Indian Ocean -- but they and other groups have been hampered by an inability to distinguish the males, which do not bite people. Female mosquitoes transmit malaria, even if sterile, so releasing them alongside males would make the situation worse.
Crisanti said: "The really challenging problem is to identify the males. There is no difference between the larvae and as adults they fly, so the logistics of trying to separate them when they're adults is immense."
To solve the problem, his team altered the DNA of the mosquito species Anopheles stephensi, the principal carrier of malaria in Asia, so that the males expressed a fluorescent green protein in their sperm.
A sorting machine based on laser light separated male from female larvae, according to whether they glowed or not. Writing in Nature Biotechnology yesterday, the scientists say the machine could sort up to 180,000 larvae in 10 hours.
The next step is to scale up the technique to provide the millions of GM insects needed to make a large-scale release effective. The scientists also need to check whether the sterile males will be strong enough to compete with wild rivals when released -- the strategy depends on female mosquitoes, who only mate once in their two-week lifespan, choosing sterile males.
Crisanti said other mosquito species could be modified in the same way, including Anopheles gambiae, which is responsible for a large part of the 2.7 million deaths caused by malaria each year. He is talking to international agencies about setting up a trial.
Scientists have previously considered releasing both male and female mosquitoes that have been genetically modified in a different way, making them unable to transmit malaria.
The idea is that altered insects would spread the disruptive genes through natural mosquito populations, but concerns about whether the inserted genes could transfer to other organisms have so far scuppered plans to set up large-scale breeding colonies to test it.
Low risk
Crisanti said that, because the new GM mosquitoes are sterilized, releasing them into the environment does not pose significant risks: "It won't transmit any genes to the environment."
"This allows us to test the transgenic technology in a very safe way that overcomes the previous environmental and safety concerns. Releasing males only would ensure people were not bitten by GM mosquitoes," he said.
Sue Mayer of Genewatch agreed that the new GM insect did address some of the previous concerns, but she called for thorough testing of the mosquitoes before they were considered for release.
"Changing one gene can some-times affect others, so there are still questions to ask," she said.
There are political barriers too. The London group's insect is best suited to tackling malaria in impoverished urban areas of southeast Asia and India, where World Health Organization (WHO) trials of sterile male mosquitoes to fight dengue fever collapsed in the 1970s amid a flurry of biowarfare accusations.
The males of the mosquito involved in the Delhi trials could be separated because their pupae were smaller, but they were never released after newspaper articles claimed the experiment might secretly be used to gather data on how to spread yellow fever.
Chris Curtis, a malaria expert with the London School of Hygiene and Tropical Medicine who worked on the WHO project in India, said: "We were all set to go and there was a huge uproar. You have to handle the public relations very carefully."
Female mosquitoes can travel several kilometers after mating, he said, so the sterile-male technique is best suited to isolated insect populations, such as in large cities.
"If females that have already mated fly in from outside your release area then they carry on laying fertile eggs. That's fatal," Curtis said.
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