'Lethal gene' to combat malaria relies on laws of attraction

Chemical insecticides are the main weapons used against mosquitoes today, but future campaigns could focus on biological warfare waged with genetically modified insects.

Oxitec, a company spun out of Oxford university in 2002, is the advance guard of this approach, using technology that inserts a "dominant lethal gene" into mosquitoes. It produces lusty but infertile males that mate with all available females; the resulting larvae die before hatching.

The strategy, tested over the past five years in field trials in Malaysia, the Cayman Islands, Panama and Brazil, is to release enough of these sterile males to swamp the natives. That means releasing many millions of insects - the number must be 10 or more times higher than the wild population.

Oxitec is focusing its research and development efforts on Aedes aegypti, the mosquito that transmits both dengue fever and the chikungunya virus that is spreading rapidly around the warmer parts of the world.

Hadyn Parry, chief executive of Oxitec, says the company's scientists have shown that the same technology can be applied to the Anopheles mosquitoes that transmit malaria, though considerable investment would be needed to adapt it to their life cycle. "We know that it is feasible . . . but we are a small company and we don't have the funding or resources," he says.

The four field trials carried out so far with Oxitec's modified Aedes aegypti mosquitoes, known as strain OX513A, reduced the number of disease-carrying mosquitoes by between 93 and 96 per cent in six months, Mr Parry adds.

OX513A contains two added genes. One is a fluorescent marker gene that enables scientists to identify any progeny from the released mosquitoes, estimate population sizes and monitor population suppression.

The other gene is designed to kill their larvae. But there has to be a way to override it so that the mosquitoes can be bred for release. The chosen antidote is the common antibiotic tetracycline, which switches off the lethal gene.

This use of tetracycline is one of several aspects of the technology on which Oxitec's opponents have seized. GeneWatch UK says mass production of GM insects in breeding factories could spread antibiotic resistance into the environment.

But according to the company, the amount of tetracycline required to breed OX513A mosquitoes is "insignificant" compared with the quantities used for veterinary, agricultural and medical purposes.

Mr Parry concedes that the technology is controversial. "There will always be people opposing us who are anti-GM in principle," he says.

The company has made most progress in Brazil, where it has received national technical approval for commercial release of OX513A from the national biosafety committee.

It also hopes to break into the US market with a field trial in Florida. The Food and Drug Administration is currently considering that application.

Mr Parry insists that the Oxitec approach is far preferable from the safety and environmental point of view to controlling mosquitoes with toxic pesticides. "It is highly targeted to the one insect species that causes harm to humans. Other insect life is untouched," he says. "Once the release of the Oxitec mosquitoes is stopped, the modification disappears from the gene pool and the environment."

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