“This is a mosquito of good”
Rob Orchard visits the Oxfordshire HQ of a company hoping to combat dengue fever – whose prevalence has grown 30-fold in 50 years – with the aid of GM bugs
Photography: Jessica Parry
Friday 21st February 2014 (Taken from: #14)
“Let him come into your house
He’s the solution
Aedes transgenic mosquito
It’s not a muriçoca [a different type of mosquito], no.
He fights dengue
And doesn’t sting anyone
Protects your health
This is a mosquito of good”
– The first two verses of a song played when Oxitec’s OX513A mosquitoes are released in towns in Brazil.
In a muggy room in an insect factory just outside Abingdon, a genetically modified mosquito is on the loose. It does not get far. After breaking out of its cage, it loops around a larvae incubator, careers past a bag of lukewarm horse blood and is heading for the door when it is abruptly cremated on an electrified fly swatter.
“It wouldn’t have bitten you anyway,” says Neil Naish, the factory’s production manager and zapper of the renegade mosquito. “Only the females bite, to feed their children. The males leave you alone.” He puts his weapon, a luminous orange racket emblazoned with the title ‘The Executioner’, on the side and continues the tour of the facility.
Oxitec’s HQ is an odd place. There are laboratories where the pheromonal fug of horny fruit flies is so thick it feels like an extra presence in the room. Where doomed insects sit in serried ranks of Tupperware boxes and lab assistants inject coral DNA into bollworm eggs, then watch them glow eerily under fluorescent light. Where scientists watch swarms of mosquitoes have sex in a box, picking out the most aggressive maters for preservation like overlords at the insect Hunger Games.
Under Naish’s direction the tanks of Aedes aegypti mosquitoes surrounding us produce 20 million eggs a week, which are then couriered off to mobile hatcheries in South America and the Caribbean. There, once pupated, sorted by sex to get rid of the females and strategically released, they fly off and mate with wild mosquitoes. And then something extraordinary happens. The resulting eggs do not hatch. The alterations made to the mosquitoes’ genome in petri dishes in Abingdon mean their offspring thousands of miles away cannot live. Within a year, populations of Aedes aegypti mosquitoes subjected to this barrage of tweaked genetic material have been shown to collapse by more than 90 percent.
And this, of course, is the endgame of the DNA-manipulating shenanigans: an insect dieback which reduces the local population of the bug so much that it can no longer act as the key vector for dengue fever, a fast-spreading and sometimes fatal disease which a recent paper in Nature estimated to infect 390 million people every year.
If you have a male insect, one of the things they are really very good at is finding a female. We are using what the male sex does well in nature.”
“Our work is based on the principle that if you release males that are essentially sterile they can mate with females but there’s no offspring” says Simon Warner, Oxitec’s chief scientific officer. “That technology was developed a good number of years ago, and it’s called the sterile insect technique. You rear insects, zap them with radiation and they limp out into the world and don’t produce viable offspring. One of the disadvantages is that the radiation weakens the adult a lot. With our technology, the males are fine, but they carry a gene that means when they mate with females there are no offspring.” The technique uses insects to seek out the targets. “Human beings aren’t very good at finding pests so they can use insecticide on them. If you have a male insect, one of the things they are really very good at is finding a female. We are using what the male sex does well in nature.”
In order to produce the infertile insects, Warner and his team add two new elements to their genome. “We start with eggs from a wild mosquito and we use micro-injection equipment to inject DNA. The DNA finds its way into the genome. Then we take the hatched larvae, analyse that, check whether our genes are in there, and we go from there.” The first gene comes from jellyfish or coral and makes the insects glow under fluorescent light. This makes it easy for Oxitec to check the progression of the infertile strain through the wild population.
The second addition is a hybrid gene from a bacterium and a virus. It makes the mosquitoes die unless they are regularly fed with the antibiotic tetracycline. Once they leave the laboratory and lose their tetracycline fix, there’s a very small window for them to find a wild female and mate with her before they fall victim to their genetic curse. “Five to six days after they’re released, and if they haven’t done their job, it’s goodbye,” says Warner.
Blunderbusses and sniper rifles
Hadyn Parry, the CEO of Oxitec and architect of the coming mosquito apocalypse, is gently amused by my question. I have asked him how it feels to be one of the few humans ever to have a realistic shot at wiping an entire species off the face of the planet. To be the 21st century equivalent of the sailor who ate the last dodo.
“That’s not going to happen” says Parry. “Let’s just look at what people are doing now. For 100 years or so, they’ve been using pesticides to try to kill all the insects that are causing them harm. While they are doing that, they hurt a lot of non-targets, they do a lot of collateral damage. They’ve been charging around with blunderbusses: we’re coming in with a sniper rifle. We’re saying, ‘If you want to take out this one insect in this one place at this one time, this is a very good way of doing it’.”
There is no risk, says Parry, of the mutant bugs spreading across the planet. “A mosquito will fly 200 yards in its lifetime. It can’t fly further, it doesn’t have the wings, strength or ability,” he says. “So you could control mosquitoes in Abingdon and you’d have no impact on Oxford [eight miles away]. You’re never going to eradicate them all. Your best goal is to eliminate them in a geographic area which you can literally draw a line around.” This containment is aided by the fact that the genes can’t be passed on: the released mosquitoes and their offspring all die, so there’s no chance of the genes spreading their way around the world over the course of multiple generations.
I ask Parry what would happen if everyone in every city in the world released the GM mosquitoes at the same time. “If all the world at the same time wanted to buy our product and do something bonkers with it, then that would raise different questions, probably more about the users than the product,” he says. “I think it’s so far-fetched as to not be possible.”
Oxitec is not currently targeting all strains of mosquito, just the dengue-spreading Aedes aegypti. All the other types, including the malaria-carrying Anopheles will be unaffected and the company has conducted studies to show that no significant new gap will be opened up in the food chain. “You have to look at all those different aspects and show solid data. If a bird was to eat one of your insects, what would happen? If you change the insects’ population what’s likely to happen? All those risk assessments have to be taken into account,” says Warner.
There is no ethical compass in industry or science any more. What’s next? Creating flesh eating zombies just because you can?” – Melissa Nichols, Houston, TX.
Not everyone has been convinced by the company’s explanations. Protests against a mooted release of OX513A in Florida were spearheaded by Mila de Mier, an estate agent in Key West, who launched a change.org e-petition in April 2012 which at time of press had gained 129,000 signatures. Comments on the site fall into four broad categories. There are the practical: “We have enough fucking mosquitoes here, we don’t need any more” – Pat Oberle Naperville, IL.
The moral: “There is no ethical compass in industry or science any more. What’s next? Creating flesh eating zombies just because you can?” – Melissa Nichols, Houston, TX.
The GM-fearing: “Let’s not play around with Mother Nature and maybe she will be nice to us” – Kathy Johnson, Milwaukie, OR.
And the plain confused: “God made mosquitoes a specific size for a specific reason” – Raven Bullard, University City, MO.
A lot of petitioners also suggest that the mosquitoes should be tested in England rather than Florida, preferably on the senior staff members of Oxitec and their families.
The company took its reception in the Sunshine State as a learning experience. “The pressure groups basically circulated scare stories” says Parry. “They bombarded the press in Florida with nonsense. It was this hilarious idea that Brits arrived in the middle of the night and released genetically engineered mosquitoes without talking to anyone. That’s what they were basically saying. The Brits are over here and they are doing this. The corollary was that the media got hold of the story, they rang up and said ‘Have you really done this?’ And then you actually have a proper, sensible conversation.”
While Oxitec was able to dispel the myth that they’d indulged in rogue nocturnal bug-releasing sprees, the GM issue, as raised by Kathy Johnson and hundreds of other signatories of the change.org petition, is harder to tackle. “We’re still suffering globally a bit of a hangover from the introduction of GM crops,” says Parry. “There is nothing entirely logical about it. There is this sort of sober, dull headache and it exists whether you talk to a politician, a regulator or a philanthropic organisation. But the way our product interacts with nature is completely different from a GM crop. With a GM crop you will get hybridisations, the spread of the gene to other crops. You’re giving the crop some kind of advantage and nature will try and preserve that advantage. What we’re doing is the complete opposite. We’re giving the biggest disadvantage you can possibly give, not to be able to reproduce. So if you can’t reproduce, you can’t go down through generations. You’re not going to get this horizontal gene type with ours.”
The Floridians might have given OX513A the cold shoulder but, according to Parry, it was welcomed with open arms in Brazil. In the city of Jacobina, it was released after a major public information campaign. “On the street, you won’t find anyone who says ‘I don’t think this is a good idea’, because they all hate dengue,” says Parry. “They are getting dengue, they are being bitten by mosquitoes and they think what we’re doing is terrific.” Dengue – also known as ‘breakbone fever’ – can bring excruciating muscle and joint pain, and in a small percentage of cases develops into the life-threatening dengue hemorrhagic fever, in which blood leaks out of patients’ veins.
Oxitec partnered with a Brazilian company called Moscamed, who took on the job of selling the concept in Jacobina through town hall meetings, school classes and events. “They set up tents in the middle of town which had cages of male mosquitoes. You could go and put your hand in the cage and not be bitten, which is really powerful. Then people would sign a book and say ‘It’s been explained to me and I’ve understood it.’ They got five percent of the population to sign, which is an enormous number in terms of public engagement.”
After the locals were on board, the releases began. A brightly decorated van drove round the town, broadcasting Moscamed’s mosquito song through loudspeakers. “Let him come into your house, he’s the solution…” In the back of the van was a man with a big box of mosquitoes. He followed a strict plan, releasing batches of insects on designated street corners.
Listen to the song here:
Within a month, inspection of ‘ovitraps’ where wild females lay their eggs showed that 80 percent of the eggs glowed under fluorescent light: they were spawn of the Oxitec mosquitoes and they would never hatch.
“People don’t eat mosquitoes”
It’s not easy setting up a transnational bug massacre. There are more than just disgruntled Floridians to be dealt with: because the technology is so new, everything has to be done from scratch.
“We are the only company that has ever asked any country to import genetically engineered insects to manufacture them and release them,” says Parry. “When we first went to the FDA (the Food and Drug Administration in the US), we said, ‘We’d like to bring in these mosquitoes.’ They said, ‘It’s not food. People don’t eat mosquitoes. And it’s certainly not a drug. You’re not going to eat a mosquito to make yourself feel better. So it’s nothing to do with us.’ Then we went to the USDA (the US Department of Agriculture) and they said ‘No one farms mosquitoes, it’s nothing to do with us’.”
Eventually, Oxitec persuaded the FDA to regulate their mosquitoes as an animal drug, which was the closest fit. With a precedent in place in the States it has been easier to gain regulatory approval in other countries. In January, Oxitec got the nod from the Panamanian government to start a trial programme in the country, which had recently announced it was experiencing a dengue epidemic. In April, the Brazilian government gave the green light for countrywide use.
And Aedes aegypti is just the start of the process. Other species in Oxitec’s sights include agricultural pests such as the diamondback moth, the tomato leafminer, the pink bollworm and the Mediterranean fruit fly. Researcher Dr Martha Koukidou is working on a GM version of the Drosophila suzukii fly, the scourge of strawberries, raspberries and other soft fruits. The new strain is currently in the “optimisation phase” which involves evaluating its fundamental sexiness to other Drosophila suzukiis. “We want them to go out there and mate, to compete with the wild males,” says Koukidou. “The better the competition parameter, the more successful the programme will be.” There are also plans for Oxitec to turn its attention to the Anopheles mosquito, chief vector for malaria. “I think there are solutions for eradicating malaria” says Warner. “We’ve pretty much got the tech but we just need to find the right programme to deliver it.”
Another future goal is to cut out the middleman and supply directly to customers. Oxitec is working on a new strain of mosquito in which tetracycline can only keep alive the male mosquitoes, which would cut out the need for mobile hatching factories. “That’s interesting because I could then send you eggs in the post,” says Parry. “If you’re an American throwing a big barbecue, what you do at the moment is you get your pest controller round at four o’clock in the afternoon and they will go round and fog everywhere with pesticide. Then your guests come at six o’clock and you can have a perfectly decent barbecue. In the future you’ll buy your packet of eggs and you’ll put them in a pot with some water, which gives them the sign to hatch out, and put it in your front garden or around your pool. Only males will fly out, they’ll mate with wild females, and soon you’ll be rid of your mosquitoes. We will be the saviours of the American barbecue.”
Oxitec may well gain stronger plaudits than this. In October 2013, University of Texas virologist Nikos Vasilakis announced the discovery of the first new strain of dengue fever in 50 years, Dengue Five. At the moment it is circulating among macaque monkeys in forests in Sarawak, Malaysia, and has only been linked to one outbreak among humans. But if it breaks out properly, it could throw efforts to find a dengue vaccine into disarray, push infection rates still higher and turn the OX513A into an unlikely global hero.
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