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    Inside the Lab That's Modifying Mosquitoes to End Disease

    Written by Bruce Douglas

    I'm not a natural scientist, a fact that's obvious as I struggle to put on a company-issued white coat and shoe covers.

    "I take it this is your first visit to a mosquito factory," Heyden Parry, the smoothly reassuring CEO of the British biotech company  Oxitec, comments drily.

    In fact, it is. But here I am, entering the laboratory which is creating the world’s first mass-produced genetically-modified animal. The goal? To control a species of mosquito that carries one of the world’s fastest spreading viral diseases:  dengue fever.

    Here, on an industrial estate in Campinas, on the outskirts of São Paulo, Oxitec is rearing millions of the  Aedes Aegypti mosquito, from egg to adult, on a diet of sugared paper and sheep’s blood.

    In the egg production room, the entire lifecycle of the mosquito is laid out in a collection of plastic beakers. First, there’s a lump of brownish granules, which, on closer inspection, are actually millions of eggs. Then come the tiny, tadpole-shaped larvae. Next, the prawn-like pupae. And finally, buzzing around in a large metal box sealed with tight wire mesh to prevent them from escaping, the fully-hatched adults. At the bottom of each box are a series of thin metal trays in which the mosquitoes lay their eggs.

    "They respond to the CO2 in your breath, so if you blow on them, they start buzzing around like crazy," Andrew McKemey, Oxitech's head of field research, tells me, exhaling strongly to demonstrate. Suddenly, it’s a mosquito Mardi Gras.

    Oxitec promotional video.

    All of the mosquitoes bred here come from OX513A, a strain of  Aedes Aegypti engineered initially at the company's headquarters, near Oxford, England, where Oxitech inserted two genes into the mosquito egg. The one contains the instructions to disrupt the normal functioning of the insect’s cells; the other is a fluorescent marker used to monitor the insect in the field. 

    Here in the lab, the lethal gene is kept at bay by an antidote not found in nature, a bright yellow liquid called  tetracycline.

    Next door, the eggs incubate in large plastic trays filled with warm water. As they develop, the male pupae are sieved from the female ones, a process made easy because the females are up to 50 percent larger than the males. It's the mature females that bite (hence the supply of sheep’s blood) and spread disease. The males, except for their irritating desire to reproduce, are harmless.

    In the third and final room are several metal shelves filled with plastic tubs, each filled with thousands of male mosquitoes. The insides of these containers have been scored with sandpaper to ensure the insects have little ledges to rest on when they are tired of flying around.

    "These pots, now they have been drained, are ready to take out into the field and be released," McKemey tells me. "These males will go out and find females as they have been designed by evolution to do over many millions of years."

    Once released, the males will try to find a mate in the few days before the antidote wears off and they die. All the eggs they fertilize will inherit the disruptive gene and fail to develop into adults.  According to Oxitec, in the field trials carried out by its local partner, Moscamed, in the northeast of Brazil, the population of the Aedes Aegypti was reduced by 96 percent after six months of continuous release of swarms of OX513A.

    To combat the disease, however, the modified males must significantly outnumber the ordinary males to ensure they are the ones passing on the lethal gene. The population of modified males also has to be repeatedly topped up to ensure they are outcompeting healthy locals. One of the major challenges, McKemey admits, is persuading the local human population that the best way to control mosquitoes is to release millions more of the damn things.

    "We do a lot of community engagement work," he says, adding that while the primary concern people have is that the mosquitoes are biting, not everyone understands that it’s only the females that bite. "One of the most effective ways of demonstrating that is to go with a big cage of males, stick your arm in there, and say, 'Look, they’re not biting.'"

    Go with a big cage of males, stick your arm in there, and say, ‘Look, they’re not biting.’

    The stakes couldn't be much higher.  Ebola might be stealing all the headlines of late, but dengue fever has killed many more people, comparatively. Around 25,000 people a year, most of them children, die after suffering flu-like symptoms, fevers, vomiting, even bleeding from the nose and mouth, according to the World Health Organization. Around 50 million people, worldwide, are affected by dengue.

    It is the fastest growing mosquito-borne disease. There is no vaccine and no cure. And Brazil, with over a million cases a year,  according to the country's health ministry, is one of the countries worse affected.

    As humans have proved a popular food source for the female Aedes Aegypti, the species tends to breed in the endless wet nooks and crannies of tropical urban cities. Up until now, the Brazilian public health authorities have attempted to manage the disease with insecticides. In theory, a genetically modified mosquito offers a much more elegant solution.

    Not everyone is convinced, however. Environmental campaigners are concerned about the unforeseen impact on the ecosystem, and believe the GM research has thus far failed to prove that reducing the number of mosquitoes will necessarily reduce the incidence of the disease. Some have also questioned whether the GM mosquito will die out as quickly as planned and argue that Oxitec-Moscamed has not addressed the consequences of accidentally releasing genetically modified, biting females.

    In her eighth-floor office overlooking the Guanabara Bay in Rio de Janeiro, I meet Maureen Santos. An environmental justice coordinator for the  Heinrich Boell Foundation, a green political think-tank, she tells me that Brazil should not become a testing ground for expensive, risky, and unproven technologies.

    "Why not, before you create a transgenic mosquito, develop some kind of public policy in this area? Waste water treatment, basic sanitation," Santos said. "It's not easy, but if you only think about the consequences, not the causes, you will never solve the problem."

    If you only think about the consequences, not the causes, you will never solve the problem.

    Back in Oxitec's factory, Parry, the company CEO, swats aside concerns about the possible unintended consequences of unleashing the world’s first mass-produced, genetically-modified animal.

    "If you think about these mosquitoes," he says, "we are releasing males. They don't bite. They don’t spread disease." After two or three days, Parry continues, they're dead. By releasing these males, then, Oxitec-Moscamed is not introducing anything "that stays in the environment." Parry says this species-specific approach to reining in the vector a debilitating virus like dengue fever, variously called backbone fever, is far less toxic to the greater ecosystem than spraying insecticides. 

    "That will kill a wide variety of insect life and the chemical will stay in the environment," he tells me. "The alternatives are more aggressive and longer lasting."

    Then again,  Oxitec admits that the risk of  inadvertently releasing females is real. But the company argues that the chances are slim, and that even if some females do manage to slip out they're still highly unlikely to develop into adults, and any disease they may carry must be seen in the context of an overall eradication campaign. 

    But what about fears the insects could potentially transfer the modified gene to humans? Parry says it's just not feasible: "Put simply, you inherit your genes from your parents, not from what you eat."

    Opponents argue it's not a question of the modified genes transferring to humans, but whether the extra proteins created in Oxitec's mosquitoes are harmful to humans or animals. 

    "Some people might have an allergic reaction," Helen Wallace, director of Genewatch UK, a nonprofit gentech monitoring group, said in an emailed statement. "We don't know, because Oxitec has not published any evidence on this in any of its risk assessments." 

    Meanwhile, Oxitec is still awaiting final clearance from Brazil's health ministry to market its mosquito. But the opening of the factory outside São Paulo suggests it is feeling pretty confident of approval.

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