by Mary Carmichael
Dr. Stephen Hoffman learned about malaria the hard way—by rolling up his sleeves and letting thousands of infected mosquitoes bite him.
© JIM YOUNG/Reuters/Corbis
Back in mid-1990s, Stephen Hoffman dipped his arm into a swarm of malaria-infected mosquitoes. But he didn’t expect to get sick. At the time, he thought he’d invented a vaccine that would keep him disease free.
He was wrong.
After Hoffman came down with a fever and the chills, he knew it was time to start over.
Today, in an unassuming Maryland office park, Hoffman and his team are breeding malaria parasites, dissecting mosquito spit glands, and working on a vaccine that might be the biggest boon to public health ever invented.
A Sticky Situation
To understand how Hoffman’s newest vaccine works, you have to understand the malaria parasite. The story begins in the salivary glands of the Anopheles mosquito, where the parasite is born. It lingers there until dusk, when the mosquito goes out to feast.
As a mosquito “bites” a human host, it spits on the skin, transmitting thousands of parasites from its salivary glands into the human’s bloodstream. From there, the parasite rides the blood vessels down to the liver, squirms into a liver cell, and then spends the next week maturing into an adult. All the while, the human victim has no idea what’s happening. There aren’t any symptoms until the end of the week, when as many as 1 million mature parasites will burst out of the liver and invade the body’s red blood cells, making the host utterly miserable.
At this point, malaria parasites wreak havoc on the body by making blood cells sticky. Cells begin clinging to the walls of the blood vessels, clogging up the flow of oxygen to the brain, kidneys, and other vital organs. For most patients, the effects feel like a really bad case of the flu—fever, chills, headache, muscle pain. But for a few unfortunate victims, things get worse. Those who contract “cerebral malaria” become confused and lethargic, and they run the risk of delirium and seizures.
The other tool is drugs, but those have their problems, too. The standard treatment for malaria is chloroquinine, a chemical related to the quinine in tonic water. Unfortunately, parasites in most malaria-infested areas have developed a resistance to it. The same is becoming true for artemisinin, an anti-malarial drug based on a 2,000-year-old Chinese herbal remedy. Malaria parasites in Cambodia have already become resistant to it. The frustrating truth is that malaria is a clever, adaptive parasite that will probably evolve its way around any drug that’s meant to cure the disease. That’s why the world needs a vaccine.
Creating that vaccine is one of the biggest challenges in modern medicine. Scientists have never developed a vaccine against a human parasite. Not only that, but malaria is also particularly devious. At each stage of its life cycle, it changes so dramatically that the human immune system barely has time to recognize it. It’s as if malaria keeps slipping into different disguises, continually fooling the body’s attack response. The issue is further complicated by the size of the parasite. It’s big—at least compared to other pathogens. Unlike viruses, which can have as few as three genes, malaria has 5,000, and many of those are constantly mutating.
So how do you attack this swirl of moving targets? Stephen Hoffman thinks he’s found an answer. His new vaccine is based on an odd phenomenon that was discovered in the early 1970s. Researchers found that if you damage the malaria parasite’s DNA by exposing it to radiation, and then allow yourself to be bitten by more than 1,000 mosquitoes infected with the damaged parasites, you’ll become immune to the disease. The result is that the weakened parasites hit a snag in their development as they enter your bloodstream. Instead of maturing and mutating, they get permanently stuck in adolescence. And because they can’t grow or evolve, the host’s body has enough time to produce an effective immune response.
Hoffman’s research found that more than 90 percent of people exposed to malaria this way became immune. But, as he puts it, “Obviously, you can’t immunize everyone by having them get bitten 1,000 times.”
These days, Hoffman is busy trying to create a marketable vaccine that mimics all those bites. His company is called Sanaria—Italian for “healthy air.” (It’s the opposite of malaria, which means “bad air.”) But standing outside the organization’s nondescript office, you’d never guess what outlandish things are going on within. Sanaria’s researchers purposely infect mosquitoes with the malaria parasite and zap them with radiation. Then, the mosquitoes are brought into a sterile room where six people in gowns and gloves sit and extract the pests’ salivary glands. (There’s a flyswatter nearby, in case a mosquito tries to escape.) It’s delicate work, but a typical Sanaria employee can dissect 100 mosquitoes in just one hour. Finally, the excised salivary glands are all crushed up and put into a test tube until they’re ready to be injected into human test subjects.
Hoffman started FDA-approved, Phase I clinical trials in 2009, and today, more than 80 adult volunteers in Maryland have been immunized. (Many of them are soldiers, since the military has a special interest in arming ranks against malaria.) If Hoffman’s formulation passes the trial, he’ll move on to Africa to perform a similar study.
Meanwhile, other researchers are also making headway on the malaria vaccine. GlaxoSmithKline, for instance, has a 50-percent effective vaccine already in Phase III trials in Africa. Of course, whoever develops the best vaccine will still have to figure out how to get it to those most at risk—populations living in developing countries that can’t afford high-priced medicine.
But Hoffman and other researchers aren’t easily deterred. The malaria parasite will kill 1 million people this year. If it isn’t giving up, then neither will they.
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