Image: Victoria Turk

London's Subterranean Mosquito Lab

Deep under London's streets, scientists are fighting to defeat one of nature's most prolific killers.

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Nov 27 2015, 4:30pm

Image: Victoria Turk

This article originally appeared in the November issue of VICE Magazine.

"I like to think of mosquitoes as these sort of ultimate bloodsucking machines," says entomologist Dr James Logan. "They're designed perfectly by nature to seek us out, to steal our blood, without us even knowing it." Logan works at the London School of Hygiene and Tropical Medicine, which is home to one of Europe's largest and most diverse collections of insects, including hundreds of thousands of mosquitoes that buzz around white mesh cages in the school's underground vaults. As director of the Arthropod Control Product Test Centre (ARCTEC), he oversees a team that works to test products that protect against mosquitoes and other insects.

But the mosquito's perfect design is constantly adapting to better fulfil its vampiric needs. In recent years, lab experiments have shown that mosquitoes can develop resistance to chemicals in existing repellents, including the widely-used N,N-Diethyl-meta-toluamide (better known as DEET). "They're so brilliantly evolved because they can overcome our toxic chemicals and become resistant to them, and that's one of the biggest problems that we have at the moment," says Logan.

Mosquito cages in the underground lab. Image: Victoria Turk

Getting bitten by a mosquito is at best irritating—at worst it can be fatal. Different species are vectors for potentially deadly diseases including dengue fever, West Nile virus and yellow fever, as well as malaria. A 2013 study Logan worked on found that members of the species Aedes aegypti, which spreads dengue and yellow fever and is regularly used in testing at ARCTEC, were less sensitive to DEET on their second exposure to the chemical.

Scientists at ARCTEC help to test products that fight off the insects by repelling or killing them. The centre works with commercial companies, regulators and other academics to develop new treatments, with some of the more unusual ideas including protective school uniforms, traps designed to lure mosquitoes to their death by mimicking nectar, and a chemical to kill even mosquitoes that have become resistant.

Before they hit store shelves, these products need to be trialled, and that's where the London lab's six-legged inhabitants come in. The school's insectaries are located directly beneath Keppel Street and Gower Street in Bloomsbury, and house mosquitoes from dozens of different strains in cages of white net. One of the underground vaults was an air raid shelter in World War II, but with the addition of heat and humidity controls it's now the perfect environment for raising baby mozzies.

Sarah Kelly in the lab. Image: Victoria Turk

"We've got Culex, Stegomyia and Anopheles down there," says scientific officer Sarah Kelly, who spends a lot of time tending to the mosquitoes in their faux-tropical bunker. The Culex genus is best known for transmitting West Nile virus, Stegomyia is a subgenus of dengue-harbouring Aedes, and Anopheles is perhaps the most infamous genus in the mosquito world: it's a vector for Plasmodium, the malaria parasite. "These are all housed in individual locations so we don't have the colonies crossing over," Kelly explains.

The lab mosquito's life cycle starts with the eggs, which the previous generation lays in a cup of water in the insects' cages. These hatch into larvae, which Kelly and her colleagues rear in plastic bowls full of water and covered in net. At this stage, they look like tiny wriggling tadpoles. The larvae shed their skins several times as they grow, before becoming pupae. They emerge as adults, all wings and bloodsucking proboscis. "Like a caterpillar would turn into a butterfly, it's the same for the mosquito—the adult emerges fully-formed out of the pupa," says Kelly.

They mate and the cycle starts again. The mosquitoes are fed on sugar and, for the females, horse blood. This is warmed using an electric heating device placed on the outside of the cage; dots of burnt red splatter the net where insects have injected their probosces through the blood capsule's skin-like membrane for a feed. Once digested, the blood provides protein for egg development—male mosquitoes don't have biting mouth parts and subsist simply on sugar, gathered from nectar in the wild.

Baby mosquitoes. Image: Victoria Turk

Some of the colonies in this vault have been going since the 1940s, originally collected from as far afield as India, Africa and Southeast Asia. As they've never been out of the lab, the present inhabitants are not infected with any parasites and so don't pose any real danger: the horse blood they feed on is treated and any insects used in human testing are left to die afterwards to avoid spreading any blood-borne diseases.

Because the mosquitoes have been reared in captivity so long, some of the colonies are now unique, having grown distinct from their wild cousins. "They're really important, because those mosquitoes have been here, they've not been in the wild, and they have important characteristics that we can then study and compare with wild strains out in the field," says Logan, who, in addition to his position at ARCTEC, is also a senior lecturer of medical entomology at the school.

But despite their long line, individual mosquitoes in the lab don't get to bask in their artificial tropical climate for long. At five to seven days old, a researcher is liable to come along with a mouth aspirator—essentially a tube with a filter in the middle to prevent accidental inhalation—and suck them off the net walls for use in a clinical trial. As only females bite, only they are selected for testing. "You do that by putting your hand on the cage," explains Kelly. "Because they're attracted to blood, they're the ones that land on the side of the cage, and you can mouth-aspirate all the ones off your hand ready for the test."

Toxorhynchites is the biggest mosquito genus in the lab, but it doesn't feed on blood. Image: Victoria Turk

There's only one real way to test an antimosquito product by the time it's got to human trials: get someone to willingly expose their skin to these hungry females. A common methodology is the "arm-in-cage" test, which I volunteered to try out. I was warned not to drink alcohol, exercise too heavily, or use scented products the day before—anything that could mess with the human odour mosquitoes are so partial to. Under Kelly's instruction, I put my right, untreated arm into a cage of 30 mosquitoes. The timer was set for 30 seconds, but almost all of the insects were on me in an instant. Safe to say, the mosquitoes were good to go. I then repeated the test with my right arm, which Kelly had applied an unmarked product to with a single gloved finger, diligently covering every square centimetre of skin. When I put my hand in the cage, it was as if the mosquitoes didn't even notice I was there.

Fascinatingly, no one's really sure exactly how repellents function, because some of the details of mosquitoes' biology remain unknown. "Even after all these years, we're only beginning to understand how they work," says Logan, giving an overview of what we know, "mosquitoes have antennae—their noses—and they're covered in receptors, and those receptors tune into chemicals in our body odour and that's how they find us." Some repellents work by blocking the receptors that pick up on human chemicals; others give off chemicals that the mosquito doesn't like.

Volunteers usually return their arm to the mosquitoes every hour over a set period of time to see how well the product lasts. More inventive treatment ideas sometimes require new test protocols. After the arm test, I try out some insecticide-impregnated clothing in a "free-flight room"—a tiled room reminiscent of a communal shower area, where I'm left to sit in a deck chair for 15 minutes while more mosquitoes try to sniff me out.

Sophie Stewart, a senior research scientist and clinical trial coordinator at ARCTEC, works to organise trials and get them approved by an ethics board. Then it's a matter of recruiting volunteers—apparently, getting people to sign up to be bitten by swarms of bugs isn't as tough as you might think. "I think it's curiosity," says Stewart. "I think we're lucky at the London School that we reach a population who are generally interested in these types of studies anyway. I have asked our volunteers what it is that makes them volunteer and generally they say it's something to tell their friends."

Would-be volunteers who meet the inclusion criteria of any particular study have to first have a single bite test to check they don't react too badly. The centre tries to reach a broad range of healthy people—male and female, across age groups and backgrounds—to get a more accurate confidence interval of how a product works across the general population. If you've ever found yourself disproportionately targeted by the little bloodsuckers when holidaying in a mosquito-inhabited area, you'll know firsthand that mosquitoes are more attracted to the chemicals in some people's body odour than others.

"You can pass on whether you're attractive to mosquitoes or not to your children"

Recent research suggests that this variable has a genetic basis. A pilot study co-authored by Logan and published this year found that identical twins were more similar in their attractiveness to mosquitoes than non-identical twins. The researchers wrote that their results "demonstrate an underlying genetic component to the human odour profile, a genetic difference that is detectable by mosquitoes through our odour and used during host selection."

"So you can pass on whether you're attractive to mosquitoes or not to your children, and it's the same level of heritability as you get for height and IQ and eye colour and that sort of thing," says Logan.

The mosquito morgue. Image: Victoria Turk

He hopes that this research could ultimately lead to the development of a new, more personalised method for controlling mosquitoes that may be resistant to other products. If scientists discover more about the genetic mechanisms that make some people mosquito-candy, perhaps they could create the opposite effect and keep the bugs away. Logan explains that people who don't get bitten produce "natural repellents", and he's even floated the idea of a pill that could enhance the body's production of these chemicals. "We know what the chemicals are, so it's just a case now of producing the product," he says.

Just as people vary in how attractive they are to mosquitoes, individuals can experience very different responses to their bites. The swelling, itch, or pain you get when a mosquito bites is caused by your own body's immune response to the compounds contained in the insect's saliva. This saliva, which the mosquitoes inject when they're probing around your capillaries, includes an anticoagulant to stop your blood clotting while they slurp it up—another neat trick of the perfect bloodsucking machines.

More aggressive mosquitoes can, however, offer advantages for the ARCTEC researchers. Both Logan and Kelly independently nominate dengue vector Aedes aegypti as their favourite species—precisely because it's so keen to attack. "They always bite; they're always working for our tests," says Kelly.

This species also bites in the daylight, while others are more active at night. That makes it easier to use in daytime lab tests, but also means it's particularly important to find new ways to protect against, as bed nets won't suffice to keep it away. Throw in its growing resistance to our existing toxic chemicals and it's a creature whose pure efficacy you have to appreciate if not admire.

Kelly says the holy grail of their work would be to find a repellent that works for everyone, against all mosquitoes, for an extended period of time. But owing to the great variability in how individuals respond to mosquitoes and repellents, she says we're "nowhere near" that point yet. For now, they're still relying on volunteers willing to be bitten for science. If you're feeling itchy just thinking about it, know that it could be worse—ARCTEC also tests products against bedbugs and head lice.

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