A Brown pathology professor may have developed a revolutionary new approach to battling one of the world’s deadliest diseases
Jonathan “Jake” Kurtis was riding a night train from Nairobi to Mombasa when he first began to feel sick. Then a 20-year-old Brown junior, Kurtis had gone to the restaurant car for a curry and stayed up late drinking beer with some Americans he’d met. By the time he got back to his sleeper car, he had a vicious headache. “I thought God had visited upon me a righteous hangover,” says Kurtis, speaking from his office at Brown, where he’s now a professor of pathology and laboratory medicine (he graduated with the class of ’89 and then stayed for a PhD in pathobiology in ’95 and a medical degree in ’96).
By the time Kurtis got to the Kenyan coast he was suffering from vomiting and diarrhea, too weak even to carry his rucksack. Somehow he got to a little mud hut he had rented on the beach. “At that point, I don’t have any memory for about three days,” he says. When he came to, he spied three open foil packets by the side of his bed. They’d contained tablets from a travel doctor to take in case of fever—taking them in his delirium may have saved his life.
Kurtis came to see the experience as a blessing. “I was lucky enough to get cerebral malaria,” he says. The disease has a fatality rate of 28 percent and can cause lifelong brain damage in survivors, who may also contract the disease multiple times during childhood, making them listless and feverish during crucial developmental years. It altered Kurtis’s life in a different way, inspiring him to devote his life to eradicating it.
Dressed in a black V-neck T-shirt and sporting tousled salt-and-pepper hair, Kurtis has an irreverent sense of humor and an easygoing bedside manner that is rare for a scientist. But he turns passionately serious when talking about one of Africa’s deadliest diseases. “I had a real epiphany, which is that malaria is a great thumb keeping the population of much of the world depressed,” says Kurtis. Approximately half a million people die every year from mosquito-borne illness, about half of them young children living in sub-Saharan Africa—one child every 2 minutes. “When you have a quarter of your children under the age of five dying, it’s unsustainable as a society.”
Malaria is a formidable foe (see the “Life Cycle of a Serial Killer” sidebar below), and to date no vaccine has succeeded in completely eradicating it from the body. This past October, the World Health Organization recommended a new vaccine called RTS,S/AS01, or Mosquirix, which it hailed as a breakthrough. Even so, trials in African countries demonstrate that the four required doses show at best 30 percent efficacy after four years—and offer close to no protective effect after that. Compare that to studies showing that insecticide-coated bed nets reduce malaria cases by 41 to 56 percent.
As fearsome a disease as malaria is, it’s long been hypothesized that some children are naturally immune. To a young Kurtis, this seemed the key to the development of a radically different kind of vaccine that might stop malaria altogether, and he’s been working to unlock the mystery ever since.
A fateful escape from the Open Curriculum
Before his transformative junior year abroad, Kurtis grew up in Portsmouth, Rhode Island, a half-hour down Narragansett Bay from Providence, attending the Catholic high school Portsmouth Abbey. He always loved science—“loved, loved, loved it,” he says. But after his strict high school experience, he felt overwhelmed by Brown’s famously flexible curriculum. “If you’re intellectually self-actualized, there’s nothing better than a school that gets out of your way,” he says. “But if you are used to running in the narrow gauge of a parochial high school, you feel like you are running off the rails.”
So when a friend returned from a cultural immersion program in Kenya, he followed suit: “I didn’t know what to do—but thought it’d be fun to think about what I wanted to do while doing that.” His project was an eight-week research project on coral reef ecology, but after his brush with cerebral malaria he switched focus to biology and earned a spot at Brown’s Warren Alpert Medical School. He had figured his quickest path to treating disease was to become a doctor—but after finding he wouldn’t be able to conduct scientific research, he regretted the decision: “I hated it!”
“I had a real epiphany, which is that malaria is a great thumb keeping the population of much of the world depressed.”
He met with his mentor, Richard Olds, director of the International Health Institute (and the same doctor who’d given him the malaria pills for Kenya) to tell him he was quitting. “He said, are you out of your mind? Don’t quit—double down!” Olds convinced Kurtis to switch to a joint MD-PhD program so he could earn his medical degree while conducting microbiology research.
Joining Olds’s lab, Kurtis focused on schistosomiasis—“schisto” for short—an intestinal disease caused by a parasitic flatworm. There he met his future wife, Jen Freidman ’92, ’96 MD, now a professor of pediatrics and epidemiology at Brown. Post doctorate, he got a research grant from Walter Reed National Military Medical Center to return to Kenya and help with early tests of the RTS,S vaccine, which the U.S. military was interested in for soldiers overseas. At the same time, Friedman got a Fulbright to work in Kenya with the Centers for Disease Control. In 1996, they got on a plane together to fly to Kisumu, a small city on Lake Victoria. It was a seminal year for them both. Driving between villages in a pickup truck, Kurtis came face-to-face with the ravages of malaria, treating children suffering from fevers or sitting listless inside their homes. The RTS,S vaccine he was testing attacks a key protein in the early stage of the disease but wasn’t showing much promise in giving immunity. While in the field, however, Kurtis had time to pursue his own idea for finding an antibody.
Kurtis had gotten the idea while at Brown, based on the work of a professor on his thesis committee, Paul Knopf. Working on schisto, Knopf investigated the response to the disease in two different kinds of rats. “Both rats made antibodies, but only one made the critical antibody that granted protection,” Kurtis says. In an effort to understand why, Knopf overlaid the genomes of the two species like a Venn diagram. They overlapped almost perfectly—with only a few exceptions. Those differences, he concluded, must be what gave one variety of rats immunity. He used this information to create a new vaccine that succeeded in immunizing rats from the disease.
In Kenya, Kurtis set out to apply the same principle. As he took blood samples from children, he noted that some seemed particularly susceptible to malaria, given the number of times they’d gotten the disease; others seemed resistant. If he could isolate the differences, he thought, maybe he could isolate protective factors that convey immunity.
Of course, children aren’t lab rats—and there were an endless variety of factors that could influence who got sick. As he took his samples, Kurtis asked questions about the children’s living situations—who lived near bodies of water that bred mosquitoes, who slept under bed nets—in an attempt to weed out reasons for their resistance or susceptibility.
“Jake’s background in basic science and his ability to apply that to populations sets him apart from other researchers,” says Chandy John, a professor of pediatric infectious diseases at Indiana University who specializes in malaria. “Unlike many of us who have a clinical background only, he has a sturdy PhD background so he can understand these basic mechanisms that might lead to protection.”
Getting malaria to kill itself
After the second stint in Kenya, Kurtis did his residency and fellowship at the University of Pennsylvania before returning to Brown as an assistant professor in 2000. He set out to analyze the blood serum he’d collected from the kids in Kenya with the help of Chris Nixon ’05 GS, ’08 MD. After controlling for confounding factors, they chose ten children who seemed most resistant and ten who seemed most susceptible, then performed a differential screening to analyze their differences.
While they came up with some interesting hits, nothing seemed definitive. Rather than give up, they applied their learning to a new set of pediatric serum samples collected by Patrick Duffy—Kurtis’s supervisor on the Kenya project—a few years later in an effort funded by the Gates Foundation. Duffy is now chief of malaria immunology and vaccinology at the National Institute of Allergy and Infectious Diseases (NIAID). This time, Kurtis and Nixon recorded even more characteristics to better identify those children most apt to hold protective factors. “He really has an unbelievable persistence,” says Nixon,