The Quest for a Malaria Vaccine and the Man Who Risked Everything to Find It

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.

These days, doctors rely on two main tools for dealing with malaria. The first are insecticide-treated mosquito nets that hang over beds. These nets are so potent that they can kill most mosquitoes on contact. But they’re also expensive to distribute, and they can wear out after a few months of use. Plus, the nets don’t always stay where they’re supposed to be; villagers often repurpose them as fishing nets, bridal veils, or whatever else they need.

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.

Fresh Air

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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10 Facts About Aspirin

Aspirin may be one of the world's best-known wonder drugs, able to do everything from cure a headache to reduce a fever, but its powers stretch beyond your medicine cabinet.

1. It's not the same as acetaminophen (used in Tylenol), ibuprofen (used in Advil and Motrin), or naproxen (used in Aleve).

2. There’s more than one way to take an aspirin. Americans swallow their tablets whole. The British dissolve theirs in water. And the French prefer theirs as suppositories.

3. The ancient Egyptians took their painkillers in the form of tree bark. Egyptian doctors used to give their patients willow bark to relieve pain because it contains salicin—the raw ingredient in aspirin.

4. Aspirin broke into the European market in 1763, after British clergyman Edward Stone chewed on some willow bark and felt a renewed vigor. He shared the stuff with his parishioners and relieved 50 cases of rheumatic fever in the process. After Stone reported his discovery to the Royal Society of London, the race was on to package the miracle cure.

5. A century later, French chemist Charles Gerhardt published an article on how to synthesize salicin in the lab, creating acetylsalicylic acid. Nobody paid attention.

6. Forty years after that, in 1897, German scientist Felix Hoffman followed Gerhardt’s process and took credit for inventing aspirin. Hoffman worked for Bayer Industries, which introduced the medicine in 1899 as the first mass-marketed drug.

7. In the mid-1940s, aspirin became a huge hit in Argentina thanks to radio jingles sung by future First Lady Eva Perón. Her country became the biggest per-capita consumer of aspirin in the world.

8. The wonder drug doesn’t just cure headaches; it can also revive a dead car battery. Just drop two tablets into the battery, let the salicylic acid combine with the battery’s sulfuric acid, and you’ve got an instant jump! Just make sure you don’t have any salt on your hands. Adding sodium to the aspirin-and-car-battery combo can cause an explosion.

9. So how does aspirin work? No one knew for sure until the 1970s, when British scientist John Vane discovered that aspirin reduces the body’s production of prostaglandins—fatty acids that cause swelling and pain.

10. Here’s another reason to eat your fruits and veggies: When the body gets a healthy dose of the benzoic acid in those foods, it makes its own salicylic acid, or aspirin.

A version of this story appeared in Mental Floss magazine.

Peter Cade, Central Press/Getty Images
How Kiss's Alive! Saved Their Record Label—And Changed the Music Industry
Peter Cade, Central Press/Getty Images
Peter Cade, Central Press/Getty Images

It was late 1974, and Neil Bogart, CEO of Casablanca Records, was falling apart. His wife of nine years had divorced him. Warner Bros., Casablanca’s onetime parent company, had cut the fledgling label loose, saddling Bogart with crippling overhead and advertising costs. The company’s headquarters—a two-story house off the Sunset Strip that Bogart (no relation to Humphrey) decorated to resemble Rick’s Café from the film Casablanca—had devolved into a hedonistic playground awash in cocaine and Quaaludes. A few years earlier, he’d made stars of the Isley Brothers and Curtis Mayfield, whose soundtrack for Super Fly had been an instant hit. Now, at 31, he was watching his career crumble.

But Bogart had a plan. As part of the split with Warner Bros., Casablanca inherited a promising project: a double LP of audio highlights from The Tonight Show Starring Johnny Carson. It seemed like a sure thing. In 1974, The Tonight Show drew 14 million viewers a night. The year before, as the CEO of Buddah Records, Bogart had sold more than a million copies of a similar compilation titled Dick Clark: 20 Years of Rock N’ Roll. Bogart was so confident in The Tonight Show project that he envisioned the album as the first of four highlight records, stretching back decades.

Before SoundScan existed to track album sales, the recording industry conferred “gold” status to any album that shipped more than 500,000 copies. Bogart shipped 750,000 copies of Here’s Johnny: Magic Moments From the Tonight Show. As it turned out, no one wanted to listen to audio clips of a late-night talk show. The album was such a flop that distributors even mailed back their free promotional copies. Industry insiders joked that it had been shipped gold and “returned platinum.” Or as Casablanca cofounder Larry Harris put it, “It hit the floor with a lifeless, echoing thud.”

By the end of 1974, Casablanca was broke. To make payroll, Bogart cashed in his line of credit at a Las Vegas casino. The label seemed doomed. It needed a cheap hit just to survive.

One of the bands on Casablanca’s roster was in similarly rough shape. Kiss, a flamboyant heavy metal outfit from New York City, had released three albums by the spring of 1975. The band had a cult following in the Rust Belt. But the moment Kiss stepped into the studio, they deflated, unable to replicate the raucous energy of their live concerts.

This may have been an impossible task. Since their first gig in 1973, the foursome had performed only in Kabuki-style makeup, black leather costumes, and towering platform shoes. Onstage, Gene Simmons, the Israeli-born bassist with a 7-inch tongue, spat fire and fake blood at the audience. Blasts of smoke and pyrotechnics punctuated hard-driving songs like “Strutter,” “Deuce,” and “Black Diamond.” At the end of each set, drummer Peter Criss rose 10 feet above the stage atop a hydraulic drum riser. This intimidating stagecraft belied Kiss’s sound: more pop than metal, closer to David Bowie than Black Sabbath on the ’70s rock spectrum. Kiss’s stage show was so over the top that Bogart pitched the band as a headline act before the foursome had a legitimate hit. Queen, Genesis, and Aerosmith all canceled bookings with Kiss because no one wanted to play after the band.

But if Kiss was a circus act, Bogart was its P.T. Barnum. At pitch meetings, he’d unleash fireballs from his hand using magician’s flash paper, declaring “Kiss is magic!” Bogart hounded DJs, TV hosts, critics, and music magazines, pushing the Kiss brand. He even convinced Kiss to record a cover of “Kissin’ Time”—a single by ’60s teen idol Bobby Rydell—as a promotional tie-in for a nationwide kissing contest called “The Great Kiss-Off.”

None of it worked. And Kiss was fed up. The band received a meager $15,000 advance for its first three albums—Kiss, Hotter Than Hell, and Dressed to Kill— and despite Bogart’s fiery efforts, it had yet to see royalties. He’d even produced Dressed to Kill himself because he was unable to afford a professional producer.

Then Bogart had an idea. What if Kiss put out a live album? It’d be less expensive than a studio recording and might preserve some of the band’s incendiary live show. At the time, live records weren’t considered a legitimate product; bands released them mainly to fulfill contracts. But Bogart didn’t care. He knew this was his last chance.

Kiss liked the concept. Within days, Bogart had arranged to record a multicity tour, with stops in Detroit; Wildwood, New Jersey; Cleveland; and Wyoming. Since Bogart couldn’t finance the tour himself, Bill Aucoin, Kiss’s long-suffering manager, put $300,000 of his own money into costumes, expenses, and effects. To oversee the recordings, Bogart roped in Eddie Kramer, a star audio engineer who’d produced albums for Jimi Hendrix and Led Zeppelin.

On May 16, 1975, 12,000 people packed into Detroit’s Cobo Hall—the largest venue in a city many considered the capital of rock ’n’ roll. Bogart and Aucoin went all out on production. To fire up the crowd, a cameraman followed the band from the dressing room to the stage, projecting the shot onto a giant screen overhead. During the song “100,000 Years,” flamethrowers wrapped the band in a curtain of fire. And this time Criss’s drum kit rose to twice its usual height.

The concerts were a massive success, yet the recordings were still mediocre. The energy was there, but the band’s musicianship suffered in its frenzied live performance. In the end, sound engineers recorded over much of the material. Nevertheless, certain core elements remain, including Criss’s drum tracks, lead singer Paul Stanley’s stage banter, and the propulsive fury of early singles “Deuce” and “Strutter,” in which the band’s energy soars in response to the sound of thousands of screaming fans. The physical record was an accomplishment of its own. A double album with a gatefold sleeve, it featured handwritten notes from the band, a glossy eight-page booklet, and a centerfold collage of in-concert photos.

Alive! was released on September 10, 1975. Five days later, Aucoin sent Bogart a letter of termination: Kiss was leaving the label. In desperation, Bogart, who’d recently mortgaged his house, cut Aucoin and the band a check for $2 million to retain them. Then everyone sat back and watched the Billboard chart.

The result was unprecedented. Alive! peaked at No. 9 and remained on the charts for the next 110 weeks, becoming the band’s first record to sell more than a million copies. By the end of 1975, major rock bands from Blue Öyster Cult to REO Speedwagon suddenly found themselves opening for Kiss. Today, Alive! has sold more than 9 million copies, making it the biggest selling Kiss album of all time.

Alive! rescued both Kiss and Casablanca from oblivion. The band’s next three albums—Destroyer (1976), Rock and Roll Over (1976), and Love Gun (1977)—were all certified platinum. In 1977, Kiss topped a Gallup poll as the most popular act among American teens. The late ’70s saw a superstorm of Kiss merchandise, including Kiss makeup kits, pinball machines, Marvel comic books, and even a made-for-TV movie called Kiss Meets the Phantom of the Park.

But Alive! also changed the music industry. “Shortly after it hit, just about every hard rock band issued live albums,” says Greg Prato, a writer for Rolling Stone and the author of The Eric Carr Story, about Kiss’s short-lived drummer Eric Carr. “Some of those albums were the best live rock recordings of all time: Thin Lizzy’s Live and Dangerous, the Ramones’s It’s Alive, Queen’s Live Killers, Led Zeppelin’s The Song Remains the Same, Cheap Trick, At Budokan.”

What makes Alive! a masterpiece, though, is how it captures the essence of Kiss—a hard rock band that was meant to be seen, or at least heard, live. “The emphasis on a live album is the experience itself, specifically how close the record translates and interprets the experience of actually attending the show,” says author and Kiss fan Chuck Klosterman. “[Alive!] jumps out of the speakers. It feels like a bootleg of the highest quality.”

Ultimately, Bogart’s excessive spending habits, along with his prodigious cocaine use at Casablanca HQ, led to his ouster from the label in 1980. By that point, he’d become the reigning king of disco, breaking such acts as the Village People and Donna Summer. He died of cancer two years later at age 39, having just created Boardwalk Records and signed the then-unknown rock goddess Joan Jett. In the decades after his death, the iconic metal band he’d helped bring to the top continues to tour, even making an appearance on American Idol in 2009. For 40 years, Kiss has been sending drum kits aloft (albeit with a different drummer), performing in fully painted faces, setting stages on fire, all in an effort to recapture an impossible sound. With Alive!, Bogart had created a chimera. It was a record that could never exist in real life: part raucous energy, part polished studio overdubs, a “live” masterpiece better than the best live act in rock history.

This piece originally ran in Mental Floss magazine.


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