By Elizabeth Landau,
Turn off the lights. Put your arms or legs on top of a cage holding hundreds of mosquitoes. Listen to news or call your mom while the critters chow down on your blood.
This was researcher Sam Rund’s routine when he used a colony of Anopheles gambiae mosquitoes, a species known for infecting humans with malaria, for research on disease transmission. A staff scientist at the University of Notre Dame, Rund studies how factors such as circadian rhythms and light affect the feeding habits of different mosquito species, which is important for understanding how they spread pathogens to humans.
The colony was picky — it wouldn’t feed on anesthetized mice or drink from a container covered with a membrane. These mosquitoes retained their behavior from the wild: They wanted blood straight from a human, and only in darkness. So Rund would feed them for about 15 minutes at a time. He’s a pro at it now; after the first two months of feeding mosquitoes, his body got used to it.
“Once you’ve blood-fed enough mosquitoes for a long enough period, you become tolerized, so your immune system, kind of, stops overreacting,” Rund said. “You definitely can still feel them when they’re biting, but the next day you wouldn’t be able to tell where I was bitten, unless you looked really carefully.”
For researchers investigating how mosquitoes spread deadly diseases such as malaria, dengue fever, yellow fever and chikungunya, laboratory protocols sometimes involve “donating” blood to the cause. And the cause is urgent — mosquito-borne pathogens kill millions of people annually all over the world. The World Health Organization has called the mosquito “the greatest menace” of all disease-transmitting insects.
Laboratories are generally moving away from feeding mosquitoes with researchers’ own blood — and special approvals from ethics boards are required, in any case, to do that. In general, researchers cannot subject themselves to feedings from mosquitoes infected with disease. But some researchers continue to allow healthy mosquitoes to bite the hands — or arms — that feed them in the name of science.
Perran Ross, a research fellow at the University of Melbourne in Australia, had a viral Twitter moment when he posted photos and videos of mosquito feeding on his arm. He told followers he had achieved a daily record of feeding 5,000 female mosquitoes, and lost 16 milliliters of his own blood — about half an ounce — to them. Fielding questions from gawking followers, he called the feeding activity “relaxing.”
Ross participates in a line of research that may help eliminate the dengue virus — which causes fever, vomiting and even death — in humans. He and other scientists have injected a bacteria called Wolbachia into the eggs of female Aedes aegypti mosquitoes. Wolbachia decreases this kind of mosquito’s ability to transmit deadly viruses, since the viruses cannot reproduce as well inside the insect’s cells. The researchers then attempt to breed new colonies of mosquitoes that have the bacteria embedded in them. This method has been showing promising results in reducing the spread of dengue in several areas.
Scientists focus on female mosquitoes because the males don’t bite humans. Females need the nutrients in human blood, such as iron, to produce eggs. Aedes aegypti females lay about 100 to 200 eggs at a time, or roughly 300 in a lifetime (adult females live up to a month; males only a week). This particular species deposits the eggs on the sides of shallow puddles, pools or artificial containers; other species may lay their eggs on other surfaces.
Ross’s cages have about 500 mosquitoes each, so he ends up feeding a few thousand per month with his own limbs. With the Wolbachia research, he uses his own blood because he needs to keep the mosquitoes under as natural conditions as possible. The colonies tend not to reproduce as well if they’re given alternative feeding sources, and getting the Wolbachia to proliferate is already challenging.
At first, when Ross began feeding mosquitoes while working toward a master’s degree in 2012, the itching was brutal; he couldn’t stop scratching for weeks. But like Rund, his body grew accustomed to it. Since then, Ross estimated, he has fed mosquitoes on the order of eight liters of his own blood.
“I’d be dead if they all fed on me at once,” he said jokingly.
Not everyone who works with mosquitoes uses the human feeding method. Chelsea Smartt, associate professor of molecular biology and biochemistry at the University of Florida, has not fed lab mosquitoes off her own arms since graduate school in the early 1990s — and that was in only special populations that didn’t adapt to other methods. She said she never got used to it.
“It was amazing to watch but uncomfortable and itchy,” she said in an email.
Smartt became interested in mosquito disease transmission because when she was 7 her family moved to Tanzania and her brother contracted malaria. Smartt’s lab looks at why certain mosquitoes can propagate viruses and transmit them to people, and some cannot.
While females need blood to reproduce, mosquitoes generally also feed on nectar. Bait stations that people can put in their yards contain sugar laced with fungi or insecticide that kill mosquitoes. Smartt’s ultimate goal is to find a molecule that attaches to sugar that would instead block a virus from replicating. That way, a mosquito bite might cause an itchy welt, but not dengue or some other disease.
“I’m trying to do a reverse vaccine,” she said. “I’d like to try to vaccinate the mosquito instead.”
Instead of human blood, Smartt’s lab uses anesthetized chickens or commercially available blood so that the mosquitoes can reproduce for research. Other labs may use mice, guinea pigs or other animals.
Other researchers tinker with various components in artificial blood to see which chemicals most attract female mosquitoes. The key to making synthetic bloodlike solution look delicious to mosquitoes is to warm it up first, says Veronica Jové, a doctoral student at Rockefeller University in New York. She puts a heated simulated bloodlike solution in a container covered with a thin piece of plastic to emulate skin. Mosquitoes then pierce this plastic with their needlelike proboscis called a stylet. The stylet is akin to a tiny syringe evolved to penetrate skin and suck up blood from beneath. Jové works in a lab that studies how the mosquito brain responds when the insect eats.
So what does human blood taste like to mosquitoes?
Jové and her colleagues have found that there are four essential ingredients in blood that mosquitoes go after: sodium chloride; adenosine triphosphate, which is the molecule of energy produced by cellular mitochondria; sodium bicarbonate, which is a major buffer in blood; and blood glucose. Based on the activity of sensory neurons in that sharp stylet, it appears they are more interested in the salty component of blood than the sweet, but all of these flavors combine to create the taste that female mosquitoes go after.
Specialized neurons in the mosquito’s stylet distinguish between blood and nectar, according to a preliminary study, led by Jové, which has not yet been peer-reviewed. Another study from the laboratory of Leslie Vosshall, a Rockefeller University Robin Chemers Neustein professor, shows that by giving mosquitoes the minimal components of the blood meal and adding a special drug, the insects will eat and later stop biting. The study was published in the journal Cell.
For Rund, who began mosquito research because of an interest in preventing diseases, feeding mosquitoes his own blood is worth it for the good cause. In addition to providing them nourishment, he is fastidious about making sure the water where they lay their eggs is clean so that new generations will hatch and thrive.
“For something that is such a scourge in the wild, sometimes they can be very difficult to keep in the lab,” he says. “While I jokingly call them my ‘babies,’ you definitely have to baby some of them.”
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