Genetically modified mosquitoes

June 30, 2012, 11:29 a.m.

This tiny insect has just feasted on human blood and one bite from it can infect you with malaria, the disease that kills 650,000 people every year. So why are British scientists playing God by breeding genetically modified mosquitoes? And are we prepared for the consequences?

A female Anopheles mosquito in flight with a newly obtained blood meal visible through her abdomen

A female Anopheles mosquito in flight with a newly obtained blood meal visible through her abdomen

It’s the middle of the day and the genetically modified mosquitoes are feeding.

The females of the species are ingesting what is known in mosquito parlance as their ‘blood meal’.

The tiny-winged insects cluster in their thousands on the small plastic dispensers of sugar solution, or hang upside down from a thin layer of transparent plastic attached to the top of their cage.

The plastic is designed to simulate human or animal skin, and trapped behind it is a film of horse blood.

There are hundreds of thousands of the insects in the small white plastic cages on the laboratory shelves in a south Oxfordshire industrial park.

The air in the laboratory is warm and there’s a smell of chemicals.

In plastic and glass containers thousands more mosquitoes are hatching in water that has a yellowish tint to it: they swarm together and move with the light every time a hand is passed over the surface of the container.

On strips of brown paper curled around inside plastic beakers and Tupperware-like boxes, there are hundreds of thousands of minuscule black dots stuck together: these are mosquito eggs.

‘This is our mosquito factory,’ says Hadyn Parry. ‘Here we practise birth control for mosquitoes.’

Parry is chief executive officer of Oxitec, a British bio-research company that pioneers innovative methods of controlling insects that damage crops and spread diseases.

Standing with Parry is zoologist Dr Luke Alphey. They are working on a new method of fighting one of the deadliest killers mankind has ever known: malaria.

It was first recorded in ancient Egypt and is still a major threat today. Parry and Alphey want to introduce their genetically modified insects into the wild in an attempt to increase the number of mosquitoes that can’t carry the disease – and drastically reduce the number of mosquitoes that can.

The words ‘genetically modified’ may alarm many people, and Hadyn Parry is the first to admit that ‘genetically modified mosquitoes can be a strange concept, a scary concept’.

 
Oxitec's 'mosquito factory' in Oxfordshire is using the technology of gene transfer to see if it can stop the mosquito from being an effective carrier of malaria

Oxitec's 'mosquito factory' in Oxfordshire is using the technology of gene transfer to see if it can stop the mosquito from being an effective carrier of malaria

Anti-GM campaigners strongly resist the idea of genetically modifying anything, mosquitoes included. The reactions from the anti-GM community to Oxitec’s work have been strident.

Pete Riley, campaign director of GM Freeze, said: ‘If you kill one family of mosquitoes, for instance, what pest will fill the void? History tells us if you start mucking around with the ecosystem, the consequences can be unpredictable.’

But Toronto bioethicist Jim Lavery, who researched the social and ethical implications of GM mosquito releases in Mexico for the Bill & Melinda Gates Foundation, said in 2011 that when it comes to a contest between genetic modification and saving lives, the choice is simple.

‘The stakes are different when people are bitten by flying things and dying.’

In its Oxfordshire laboratory, Oxitec is using the technology of gene transfer, more commonly known as genetic modification or genetic engineering, to see if it can stop the mosquito from being an effective carrier of malaria.

It’s an urgent business: for each minute the two men stand in front of the mosquito cages, an African child dies.

Some 216 million cases of malaria are contracted every year, responsible for 655,000 deaths in 2010, according to the WHO’s World Malaria Report.

New figures released in February by the Institute for Health Metrics and Evaluation at the University of Washington suggest the deaths could actually be double that, with more than 40 per cent of those unexpectedly being older children and adults.

It’s a disease that is not picky: it can just as easily be contracted by Britons, celebrities included, visiting malarial areas in west Africa and Asia.

Luke Alphey, chief scientific officer at Oxitec

Luke Alphey, chief scientific officer at Oxitec. Some 216 million cases of malaria are contracted every year, responsible for 655,000 deaths in 2010, according to the WHO's World Malaria Report

Cheryl Cole famously collapsed on a photo shoot in 2010 after contracting malaria while on holiday in Tanzania: at one point she was given only 24 hours to live.

Chelsea striker Didier Drogba, from the Ivory Coast, caught it too, as did Ross Kemp, who lost 33lb in a week following a visit to Africa; he described the illness as ‘my worst experience on holiday’.

 

British travellers returning home have the second-highest contraction rate of malaria in the EU after France, says Malaria No More UK, a leading British charity.

The number of cases recorded from 2008-2010 shot up by 30 per cent to 1,761, according to the UK Health Protection Agency.

Malaria sufferers over the centuries have included Genghis Khan, Dante, Oliver Cromwell, Lord Byron, Nelson, Trotsky, five Popes, eight U.S. presidents, including George Washington, and Mother Teresa.

Working as a foreign correspondent in Africa I contracted it twice in Sudan in 1998. I’d been taking every form of malaria medication then available but the mosquitoes had developed some immunity to Mefloquine and Chloroquine.

By the time a small single-engine aircraft chartered by an aid agency evacuated us out, my liver was heaving with Plasmodium parasites.

‘There are so many parasites in your blood it looks like boiling water,’ a Kenyan doctor said in Nairobi.

I can remember a nurse spooning baked beans into my mouth as I lay hallucinating in sweat-soaked sheets, vomiting and convulsing, my temperature hitting 105, fainting every time diarrhoea dragged me to the bathroom.

In the run-up to World Malaria Day on April 25, the fight against the disease continues to be waged on all fronts.

A revolutionary new malaria vaccine is being trialled and developed by scientists, Britons included.

But although trials suggest the vaccine, ‘RTS,S’, can halve the number of deaths in children between the ages of five and 17 months, developing it takes decades and costs millions.

Pupal stage of a male Anopheles mosquito, visualised under the light microscope

Pupal stage of a male Anopheles mosquito, visualised under the light microscope

Money for this and other solutions is pouring into malaria research from the Gates Foundation, while celebrities such as Jeremy Irons and Annie Lennox campaign on behalf of the Global Fund.

The official line from the Gates Foundation is that ‘the fight against malaria is threatened by growing weaknesses of current tools.

'Mosquitoes are becoming resistant to insecticides used in bed nets and sprays, and malaria parasites are becoming resistant to today’s drugs. New methods for controlling mosquitoes are urgently needed if malaria is to be eradicated.’

 

Dr Alphey believes his plan for genetic modification will work. After all, it’s already been tested.

Two years ago he flew to the Caribbean island of Grand Cayman with a team of his staff to carry out a revolutionary experiment. He had an unusual item in his luggage – 20 million GM mosquito eggs, enough to half fill an average-sized coffee cup.

Their target: the mosquito population of Grand Cayman that spreads Dengue fever, another virus-borne tropical disease.

The eggs had been genetically modified back in the UK so that the male mosquitoes they produced would be sterile and thus incapable of fertilising the wild Cayman females. It is the females that bite.

When a female mosquito is laying eggs, she needs extra protein, which she gets by sucking blood, 100 times richer in necessary nutrients than nectar from flowers.

She gets her ‘blood meal’ from animals, birds and mammals, and if the organism she is feeding on is carrying the single-celled Plasmodium malaria parasite, she picks it up.

It is then fertilised inside her gut, transferred to her salivary glands, and the next time she feeds she transfers the parasite to the recipient’s bloodstream. Male mosquitoes do not even have the correct mouthparts for biting.

GM mosquito larvae engineered to produce fluorescent proteins so they are distinguishable from those in the wild

GM mosquito larvae engineered to produce fluorescent proteins so they are distinguishable from those in the wild

The eggs were hatched in a local rearing unit on Grand Cayman, and then released into a 40-acre test area in a suburb of the Grand Cayman capital.

The aim was to reduce the local population of the Dengue-carrying mosquito Aedes Aegypti. No more room than 40 acres was needed: mosquitoes very rarely fly more than 200 yards from the point where they are hatched. The newly arrived mosquitoes had all been released by July 2010.

The target population then started to decline sharply in August, and by October it was estimated the local female population had dropped by 80 per cent.

At Imperial College in London, Andrea Crisanti, an Italian professor of Molecular Parasitology, has been working on gene transfer technology with mosquitoes for ten years.

With £13 million of funding from the Gates Foundation, Crisanti is working on disrupting the sex ratio in the malaria-carrying Anopheles mosquito.

‘Our genetic modification consists of putting in a gene that codes for the PPO1 enzyme,’ says Crisanti.

PPO1 is an enzyme, he explains, that like a shredding machine is able to destroy the X chromosome during gametogenesis, the process by which cells that specialise in sexual reproduction are produced, leaving only the Y, or male chromosome, active.

The aim is to produce a predominance of male mosquitoes that cannot therefore transmit malaria.

 

On paper, and then in practice, Oxitec’s trial release against the mosquitoes in Cayman looked great. The initial and highly successful targeting of the much more deadly Anopheles could then begin in earnest.

Scientists carried out another smaller but no less successful release in Malaysia, and are currently working with the Brazilian government for an imminent mosquito release there.

Possible mosquito releases could also take place in the Florida Keys this year, and in the next three years a full release in Africa is planned.

But parts of the scientific community, taken by surprise by Oxitec’s revolutionary mosquito release, the world’s first, continue to be up in arms.

Lucia Ortiz, of Friends of the Earth in Brazil, where Oxitec plans a release, said: ‘Oxitec is using poor regions in the global south, such as cities in the north-east region of Brazil, as its laboratory for genetically modified mosquitoes.’

 
Cheryl Cole suffering symptoms of malaria backstage at The X Factor, 2010

Cheryl Cole suffering symptoms of malaria backstage at The X Factor, 2010. She contracted the disease while on holiday in Tanzania: at one point she was given only 24 hours to live

A UK-based watchdog, GeneWatch, says Oxitec’s trials in Malaysia and Cayman were unethical and undertaken without the consent of local people: but Oxitec states it was formally invited to carry out the trials.

The second argument GeneWatch put up is the fear that the Asian Tiger mosquito, Aedes Albopictus, could move into the ecological niche vacated by Anopheles (if GM technology helps reduce its numbers significantly) and carry on its deadly work.

But Dr Chris Drakeley, senior lecturer in Immuno-Epidemiology and director of the Malaria Centre at the London School of Hygiene and Tropical Medicine, says ‘there’s no evidence other species of mosquito apart from Anopheles can be infected with and transmit Plasmodia.’

The debate and the trials will continue. Even if British scientists do continue to let loose their GM mosquitoes, the potentially lethal Anopheles will not become extinct.

But they hope the number of males who don’t bite and spread disease will expand exponentially over 15 or 16 mosquito generations.

Dr Heather Ferguson of Glasgow University adds a note of caution: ‘Of particular note is our almost complete ignorance of the mating biology of male Anopheles.

'This deficit poses serious obstacles to the success of malaria-control programmes based on the release of mass-reared male mosquitoes into the wild.’

Entomologist Dr James Logan, a lecturer at the London School of Hygiene and Tropical Medicine, adds: ‘This type of research could theoretically have a large impact in the fight against malaria.

'It’s exciting to see that much of the science has been pinned down, but what matters most is what will happen when scientists take this to the field – only then will we know whether this type of control tool will make a difference.’

Any research can only be good news. I survived, but in the two weeks I had malaria, statistics show that 15,000 children on the continent around me would not have made it.



Read more: http://www.dailymail.co.uk/home/moslive/article-2121584/Mosquito-factory-Can-malaria-stopped-British-bred-genetically-modified-mosquitoes.html#ixzz1zILA9BMS

 

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