BATTLING MOSQUITO MENACE
Winnipeg lab and British company hatch a plan to tackle disease-carrying pests
In the unofficial mosquito capital of Canada, most people do whatever they can to avoid the clouds of biting, whining pests. Steve Whyard, on the other hand, is creating mosquitoes by the thousands.
Inside his Winnipeg lab, the University of Manitoba biologist is soaking larvae of one of the insect’s most dangerous strains in a special solution to “silence” two of the bugs’ genes.
The result is an army of sterile males with potential to infiltrate and decimate whole populations of mosquitoes.
That’s good news for the battle against summer insects. And, more significantly, could finally give humans the upper hand on illnesses that kill hundreds of thousands annually. But the experiment also launches Canada into a controversial new field — bioengineering — that critics fear might also wreak havoc on humans.
A British company’s proposal to release millions of its genetically modified insects into a Florida Keys community in the near future has stirred up vocal opposition, with 150,000 residents signing a petition to oppose the project.
“They are going to use my kids, my neighbours and my community as a guinea pig,” says Mila de Mier, the Key West realtor who launched the petition. “I’m not a scientist, but I do have common sense. How many times in nature do you get unintended consequences?”
Many scientists do not share de Mier’s worries of inadvertent environmental calamity, and Whyard says his technique avoids the GM controversy entirely.
But some kind of disruptive technology would seem called for to counter what remains the world’s deadliest animal.
Despite significant progress over the last decade, the malaria delivered by anopheles mosquitoes is still to blame for 600,000 deaths a year, predominantly among young children and pregnant women. Dengue fever spread by the Aedes aegypti species — the one targeted by Britain’s Oxitec and Whyard — kills 25,000 people annually and sickens up to 100 million more, with cases soaring 30-fold in the last five decades.
Canadians are vulnerable to those and other mosquito-borne diseases when they travel — and to West Nile virus at home.
The tools that have curbed malaria so far — insecticide-soaked bed nets, drug treatment and rapid diagnostic tests — are unlikely to bring more dramatic gains, says Fil Randazzo, deputy director of translational science at the Bill and Melinda Gates Foundation.
And until the foundation’s goal of malaria eradication is achieved, the spectre of the disease rebounding to previous levels remains a distinct possibility, he said.
Vaccines and a one-dose treatment are among the next generation of weapons against malaria, but no magic bullets. Vaccines are also being developed for dengue, though none have shown more than about 50 per cent efficacy.
Meanwhile, reports of resistance to commonly used insecticides are growing.
Taking the battle against such diseases to the next level, say many experts, requires attacking the pathogens’ distribution networks — that minority of mosquito species that spreads illness.
“If you really want to suppress the populations, you either need a technology like (GM), or you’re going to be spraying a hell of a lot of pesticides, which we know is not a solution,” says Murray Isman, an entomologist at the University of British Columbia.
The so-called sterile-insect technique — releasing a fifth column of infertile bugs into the wild population to mate and at least slow down reproduction — has been used for several years, mostly for farm pests. But the traditional sterilizing method of irradiation leaves males weakened in the competition for mates.
That’s where genetic modification comes in.
So in addition to its many other projects, the Gates Foundation has invested $60 million into mosquito “precision genetic techniques” that it believes is promising, if still
experimental.
“What genetic technology has done is, rather than using a sledge hammer to sterilize mosquitos, it’s just targeting one gene in the organism,” said Randazzo.
The most commercialized technology so far comes from Oxitec. The company adds two synthetic genes to mosquito eggs: One ensures that when the males mate, their offspring die in the larval stage; the other produces a fluorescent colour that helps the firm monitor its DNA-adjusted larvae in the field.
The company has held trials in which it released millions of mosquitoes in Malaysia, Cayman Islands, Brazil and Panama. In each case, the local population of aegypti crashed by more than 90 per cent, well below the level at which they spread dengue, contends Haydn Parry, Oxitec’s CEO.
But environmental groups and other critics are alarmed.
They note that few if any of Oxitec’s trial results have been published in peer-reviewed journals, though Parry said independent researchers are in the process of doing so.
Nor has Oxitec studied whether the releases have actually resulted in reductions in disease spread.
Opponents like Helen Wallace of Gene-Watch UK note that a dengue emergency was declared in Jacobina, a Brazilian town where one of the trials took place.
Parry responds that the experiment covered only about 15 per cent of the town’s mosquito population, while the company is trying to figure out how to measure dengue reduction in the small areas it releases mosquitos.
Still, Wallace charged that Oxitec has been less than transparent, failing to conduct the risk assessment she said European Union rules require before exporting genetically modified insect eggs, and not conducting human-safety tests.
Among her fears is that antibiotics used in the process could enter the environment and increase drug resistance. Another is that proteins expressed by the genetically modified genes could cause unknown allergic or toxic reactions when people are bitten.
The UBC’s Isman argues there is little biological evidence to justify the critics’ worst-case scenarios, though he understands the anxiety.
“People fear the unknown,” he said. “But the scientific community is pretty strongly, favourably disposed to the appropriate, careful use of technologies like this.”
It is improbable, for instance, the modified DNA would even get into the saliva that mosquitoes transfer when they bite, let alone prove toxic, said the entomologist. Severe allergic reactions are much more likely from a honeybee sting than any mosquito, Isman said.
And the more ominous worry that genetically engineered mosquitos could somehow change the DNA of humans and other animals that swallow or are bitten by them — or create other mutations in the mosquitoes themselves?
“You’re going to end up with mosquitos the size of sparrows or something? I think we understand molecular biology well enough to say that the likelihood of those things happening is infinitesimally small,” says Isman.
In the U.S., meanwhile, the Florida Keys Mosquito Control District invited Oxitec to try out its technology in the town of Key Haven. The general area — though not Key Haven itself — has seen cases in recent years of dengue and chikungunya, an emerging and painful virus spread by the same mosquito, and pesticides are having limited effect.
The U.S. Food and Drug Administration is now assessing the company’s proposed trial.
Others, like the World Health Organization, say the technology could be useful, but requires more study. Scientists need to show “they could reduce malaria without adverse effects on human health and the environment,” said Sanni Yaya, a health economics professor at the University of Ottawa who has studied malaria’s devastating impact on African countries.
Winnipeg’s Prof. Whyard says his own group’s innovation may circumvent the whole GM controversy — and still deliver effective mosquito sabotage.
As described in a recent paper in the journal Parasites and Vectors, his technique leaves the relevant fertility and female-sex genes unmodified, while using “RNA interference” to stop them from producing proteins that tell other cells what to do.
It means the larvae generate few females — the only sex that bites and passes on disease — and the males that are born fire blanks when they mate with wild mosquitoes.
Whyard hopes to find a commercial partner, and be able to start field trials within two years.
It makes most sense to use the technology to combat diseasecarrying mosquitos, he says, but it could conceivably be deployed against the merely annoying kind — like those that victimize his fellow Winnipeggers every summer.
“For the average person on the street,” says Isman, “I think they’d say ‘Get rid of the mosquitoes altogether.’”