Invasion of the warrior insects
By Clive Cookson
Financial Times, October 11 2008
http://www.ft.com/cms/s/0/f479459c-9347-11dd-98b5-0000779fd18c.html?nclick_check =1

Scientists are about to unleash a new weapon in mankind's running battle against insect pests: a genetically modified flying army. The first commercial release of GM insects, to protect US cotton fields from the voracious pink bollworm, is expected within the next two years. The second target will be the mosquito that spreads dengue fever in Asia.

This new airborne offensive is being mounted from a business park near Abingdon, Oxfordshire, where a set of low-key laboratories houses the world’s leading centre for GM insect development. Oxitec, a private company spun out of Oxford University in 2002, holds tens of thousands of moths, mosquitoes and flies in its insectaries. They are undergoing genetic engineering as part of the fight against agricultural pests and carriers of human disease.

GM is being deployed to extend the "sterile insect" technique that has already successfully eradicated pests such as screw-worms and Mediterranean fruit flies (medflies) in parts of north America. The idea is that vast numbers of sterile yet virile males at least 10 times as many as the wild population are released in infected areas. These sterile newcomers swamp the native males, mating with all available females, which then fail to produce any offspring.

Until now, insects have been sterilised before release by old-fashioned irradiation from radioactive isotopes. But this is a crude technique that works only on some species. "It doesn't work for mosquitoes because a radiation dose big enough to sterilise the insect will also incapacitate or kill it," says Luke Alphey, founder and research director of Oxitec.

With colleagues at Oxford University he discovered how to achieve the same effect more gently and specifically, by inserting a "dominant lethal" gene into the insects. "The males produce viable sperm which will fertilise the egg, but the embryo [larva] dies in development," says Alphey, who left the university this year to work full time for the company.

"Of course the system needs to be reversible, so that we can breed the insects in the first place," he adds. This is achieved by designing the lethal gene so that it can be suppressed by adding the antibiotic tetracycline to the captive insects' diet. In the absence of tetracycline, the larvae die.

The lab insects live in clear plastic containers of various shapes, typically about the size of an archive box. Some have fine mesh or gauze on one side. Fruit flies, for example, lay their eggs on the mesh, where they can easily be collected by lab staff.

Female mosquitoes receive what's known as their "blood meal", which they need to breed, through the gauze. Genevieve Labbe, who is in charge of the mosquito breeding programme, gives them horse blood heated to 37°C, twice a week. "First we blow into the cage to tell them there's something to bite," she explains. Carbon dioxide in the breath alerts the insects to the presence of a warm-blooded animal.

The mosquitoes, which have been sitting or flying lethargically around their box, begin buzzing energetically in response to Labbe's breath. Then a cylinder of warm blood, with one end covered with sausage skin, is placed against the gauze and the mosquitoes gorge themselves.

Oxitec's highest-profile project is to attack Aedes aegypti mosquitoes, the carriers of dengue fever, which afflicts an estimated 100m people every year. The work is funded with a $5m grant from the Bill & Melinda Gates Foundation, part of the charity’s drive to reduce the toll from tropical diseases.

"Both the incidence and severity of dengue are increasing," warns Alphey. "There are no drugs or vaccine, and $1bn has been spent - largely ineffectively - on dengue control through insecticide fogging and site sanitation." (The mosquitoes breed in small rainwater pools, such as those that form in discarded tyres.)

The Malaysian government is collaborating with Oxitec to run a field trial with GM insects on Pulau Ketam, an island east of Kuala Lumpur inhabited mainly by Chinese fishing families. Its relative isolation makes Pulau Ketam a good test site, because were Aedes aegypti to be suppressed locally, the success would not be masked by mosquitoes moving in from elsewhere. But some residents are objecting to what they call "warrior" mosquitoes.

"What else will the 'warrior' mosquitoes kill?" asked Saw Lek, a retired teacher quoted in the South China Morning Post. "We fear, once released, there is no way to control the new mosquito if anything goes wrong."

There are also objectors further afield. Mae-Wan Ho, director of the Institute of Science in Society, based in London, calls the use of "terminator mosquitoes" to control dengue "dangerous and costly". She believes there is a risk of the lethal genes moving from the released GM mosquitoes into other organisms and disrupting the already fragile environmental balance.

But Oxitec scientists insist their GM mosquitoes are environmentally benign. First, they argue, only the non-biting males are released; they are easily sorted from the females in the breeding facility because their pupae are smaller.

"The natural population density of Aedes aegypti is not high," says Alphey. "For a city of 1m people you are probably talking about releasing 10-20 mosquitoes per person per week. I don't think anyone would notice the increase in the mosquito population."

He points out too that Aedes aegypti, like the other pests targeted by Oxitec, is not a native species (it originates in Africa) but has been spread around the world by human activities. Its eradication would not disrupt any local ecosystems. “There is no breeding route into a wild population,” Alphey insists. And if the terminator gene does inadvertently get into wild mosquitoes, it "absolutely will not spread", because any insects carrying it would not survive.

The promise to keep genetic modification out of the wild population may make the Oxitec technology more acceptable to sceptics than other ways of using GM insects, which are being studied but are further from commercial application. Scientists at Imperial College London, for example, plan permanently to change the genetic make-up of wild mosquitoes, so that they can no longer transmit a human pathogen such as the malaria parasite.

Safe or not, GM technology will get nowhere without winning over the people living near release sites, warns Anthony Wilson, an expert on insect-borne disease at the UK-based Institute of Animal Health. “If you can see a facility releasing clouds of mosquitoes, you’ll want to be very sure that you are not just being used for experimental purposes,” says Wilson. In the 1970s, long before scientists could genetically engineer insects, the World Health Organisation and the Indian government had to cancel an ambitious dengue control project after local newspapers caused a furore with erroneous claims that it was a camouflaged US germ warfare experiment.

In the US, Oxitec’s pink bollworm project is not meeting hostility, partly because American public opinion is less suspicious of genetically modified organisms than Asian and European. Another reason is that the GM insects released in the US would replace insects sterilised by irradiation in the fight against cotton bollworm, rather than adding millions of new insects to the existing population. “We have had three years of field trials, releasing our GM pink bollworm from the air over cotton in Arizona,” says David Brooks, Oxitech chief executive. “We had a very positive environmental impact report [from the US Department of Agriculture] and we could go into commercial operation next year or in 2010.”

A bigger prize in the agricultural sector would be the medfly, a scourge of fruit-growers worldwide. Oxitec hopes the US government will eventually adopt GM technology to replace the irradiation facilities that it is funding in central America to push medfly further away from the US. The sterilisation plant in Guatemala produces a staggering 2bn sterile flies every week that’s 20 tonnes of living insect.

Once the GM medflies have proved themselves in field trials, the US authorities, nervous about the potential security risks posed by radioactive sources, may indeed prefer the cleaner and simpler technique of genetic sterilisation. But it is hard to imagine GM insects being released in Britain or Europe for the foreseeable future. If activists are determined to trash static biotech crops, imagine the uproar that would greet GM on wings.

Clive Cookson is the FT's science editor.