It’s World Malaria Day. There’s been great progress against malaria over the past decade but most experts agree the best hope is to find an effective vaccine. Seattle Biomed is one of the world leaders in malaria vaccine research, but testing these experimental vaccines relies on people volunteering to get the vaccine — and get bitten. What it’s like to get infected for science.
By Cyan James, special correspondent
“I’m going to get infected and I’m going to love it,” Lane Rasberry says with a smile.
Rasberry is about to spend at least five minutes with more than a dozen mosquitoes full of malaria parasites.
The mosquitoes huddle in a screened, pint-sized container, waiting for Rasberry to roll up his left sleeve, lay his forearm over the container, and drape a towel over his arm to simulate night. Then they launch, feeding on Lane until their breakfast clock runs out.
A Wikipedia editor by day, Rasberry also volunteers in a malaria vaccine trial at Seattle BioMed, where he belongs among a unique group of clinical subjects who intentionally get infected.
Why? For Rasberry, it’s because the research is both altruistic and convenient, and because it plays to his interest in science. “I actually enjoy participating,” he says, emphasizing research trials’ ability to create community and help others learn about scientific advances. Plus, since he grew up in Texas, the mosquitoes don’t really faze him.
After Rasberry’s five minutes are up, a technician dumps his mosquitoes into an ethanol bath to kill them, then flicks off the mosquitoes’ heads, presses their torsos to extrude their innards, and swiftly isolates their salivary glands.
The technician scans the tiny sickle-shaped glands under a microscope, searching for P. falciparum, the parasite that infects up to 500 million people with malaria every year and kills nearly two people every hour.
Rasberry’s blood is tested to determine how his body reacts to the parasites. He belongs to the most recent phase of the vaccine trial and is developing immunity, so he doesn’t expect to experience any malaria symptoms. This is his third time bitten (challenged, as it’s called) and he’ll go back for another round if the first batch of mosquitoes didn’t bite adequately or inject enough parasites.
Despite the potential annoyances—hours spent being screened , frequent health checks, irritating bites, painful twice-daily blood draws for weeks, not to mention the slamming headaches and vicious chills of malaria itself—people like Rasberry say being a malaria trials volunteer is worth it.
Compensation, the chance to ask researchers extensive questions, and personal interest lured in volunteer Tristan Victoroff after he saw a poster advertising the trials with the headline ‘Hope has never been more infectious’.
“Malaria is a really complicated bug,” Victoroff says. “It’s just fascinating and tragic, and it’s been with people all the way back to the time of the Egyptian pharoahs.”
For graduate student Bill Wood, the research simply sounded fun and promising. Others cite motivations including the chance to interact with a parasite that once infected their grandparents during combat, the satisfaction of helping humanity stay healthier, or just the chance to scratch an itch for scientific knowledge.
Whatever their reasons, around 70 participants have been admitted into Seattle BioMed’s malaria trials so far.
Victoroff, who studied public health genetics, wrote his master’s thesis on how people’s genes predicate their response to antimalarial drugs. He found Seattle BioMed’s malaria-fighting strategy captivating, even though he has doubts that a vaccine is ultimately a tenable way to defeat malaria.
Instead of focusing on drugs to treat malaria, Seattle BioMed has mustered a cross-disciplinary team of geneticists, statisticians, doctors, bioinformaticists, and even the odd game designer in a systems biology approach to developing an effective malaria vaccine. The research organization regularly networks with PATH, the Bill & Melinda Gates Foundation and other global health experts to share knowledge and collaborate; they also contract with other researchers in conducting clinical trials in addition to running their own.
Malaria is no easy target. An infected mosquito can easily spit a bolus of P. falciparum parasite into a human’s bloodstream while feeding. But the parasite doesn’t stop in the blood, as was once thought. It also dens up in the liver and multiplies before heading back into the bloodstream in a two-step dance that often turns deadly.
Seattle Biomed’s Malcolm Gardner believes the liver is a key bottleneck where scientists can block parasites. His colleague Stefan Kappe deletes certain genes from malaria parasites to see if he can halt their growth in the liver stage, tripping up their infectious dance while conveying immunity and ending the headaches, chills, shakes, and anemia familiar to malaria sufferers.
Researchers are currently developing novel vaccines that incorporate these genetically altered parasites. The most advanced malaria vaccine to date, known as RTS,S, offers only about 50% protection—a protection level some believe is promising, while others claim there is still room for improvement.
“There’s no golden bullet,” Gardner says. But he notes that unraveling the parasite’s genetic code means researchers “aren’t working blind anymore.” Gratifying vaccine results have been observed so far in mice, though these vaccines have not been completely analyzed in humans.
Clinical trial investigator Sara Healy says a malaria vaccine trial can take at least three to four years from ideation to completion, and cost four to five million dollars. Funding comes from the National Institutes of Health, the Gates Foundation, and more than 500 foundations, corporations, and private contributors.
“We’re not just giving people malaria to see what happens,” says Healy, pointing out that each trial is carefully designed to advance knowledge of malaria’s molecular biology while protecting volunteers by adhering to a spotless malaria trials safety record.
Now in its 36th year, Seattle BioMed grows its own mosquitoes, investigates malaria in mouse models, runs a series of research labs, and recruits volunteers like Rasberry, Victoroff, and Wood for human trials. Only three other facilities around the world are similarly equipped to run human malaria trials, due in part to the challenges of raising mosquitoes on-site and of complying with stringent research protocols.
Before testing vaccines, Seattle BioMed first had to prove it could reliably cure malaria in its volunteers.
In the first trial phase, Victoroff and five other volunteers were bitten by infected mosquitoes and monitored until parasites surfaced in their blood. Victoroff’s blood contained such high parasite loads it was plated onto slides for training technicians (though, Victoroff ruefully notes, he has yet to look at one of these slides himself.)
After being infected, the volunteers were whisked into a hotel suite made over into a laboratory complete with microscopes, plastic-draped floors, and noise-cancelling machines. Clinical specialists handpicked for their expertise treated and monitored volunteers as they rode out their infections in the hotel.
Victoroff knew he had malaria once a savage headache took hold. Then came waves of chills not even the hotel hot tub could dispel.
“You feel like your blood cells are popping,” he remembers.
Wood, who participated in the second stage of the trials, says having malaria is extremely tiring, even though the researchers halt volunteers’ infections as soon as possible. Seattle BioMed gives its volunteers a form of malaria that can be cured by classic drugs like chloroquine. More dangerous, drug-resistant forms of malaria exist, but aren’t used in the studies because of the health risks.
Shortly after their infection is confirmed, volunteers take anti-malarial drugs that quench most symptoms within a few days. Volunteers aren’t infectious to others, and don’t anticipate lasting side-effects, even though right afterward it feels, as Victoroff recalls “like I pulled several all-nighters in a row.”
The worst part, Rasberry says, surveying the reddish bites that pock his left forearm, is actually the extremely adhesive tape that secures the needles used during his blood draws. The best part, Wood says, is getting to tell people about the malaria trials afterward.
After all, it’s not everyone who lets mosquitoes bite for the good of others.
Cyan James is a freelance writer and graduate student at the University of Washington studying public health and genetics. More about her at www.cyanjames.com or @CyanJames.