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As flu season arrives, so may renewed concerns about the possible emergence of a future, global killer virus. Donald S. Burke, dean of Pitt’s Graduate School of Public Health, has made a career of hunting dangerous viruses. He knows the perils and the promise.

Danger Zone


Bo Schwerin


 
  Donald S. Burke (David Schrott photo)
   

Black flies hum on the banks by the ferry crossing. The same iridescent color as the water, they lift up in aimless spirals like wild droplets cast from the river. On the far side, the road disappears into Cameroon’s curtain of dense-forest green. Donald Burke, a physician and researcher, waits while a land cruiser is eased onto the broad wooden ferry. From under the shadow of his wide-brimmed hat, he watches the flies with attentive concern, the way a passerby watches a dog in an open yard, gauging the threat.

He checks his sleeves, buttoned tightly around his wrists despite the wet-blanket heat of this African wilderness. He knows the tragic consequences that can arise from the welt of a single insect bite: malaria, yellow fever, dengue, river blindness. He knows too that, sometimes, even years of experience and the best precautions aren’t enough.

Burke is here to seek what would drive most away—a deadly infectious virus that has killed many millions of people and continues to infect others at an alarming rate. The physician is pursuing the original source of HIV, the human immunodeficiency virus, which causes AIDS.
What he learns in the forests of Cameroon leads him on a quest that could, one day, stop other emerging killer viruses.

At the river crossing, the land cruiser rumbles off the ferry, carrying Burke and some of his research colleagues. They’re traveling to remote villages in search of the secrets of the growing, global AIDS epidemic. At each village, Burke takes blood samples and conducts field interviews. Early on, he makes some observations. He notices, for instance, how frequently the villagers hunt for bush meat—jungle animals, including primates. He watches the men butcher their daily catches, getting blood and occasional cuts on their hands and arms.

From his work as a researcher, he knows that chimpanzees and other nonhuman primates carry strains of a virus that resembles HIV in humans. As he observes the Cameroon villagers in such close proximity to apes and other bush animals, Burke ponders the possibility that the virus in these primates is somehow crossing into humans. That would explain a lot in his long hunt for the source of the killer virus.

At the start of his career, after earning a degree from Harvard Medical School and completing several medical residencies in Boston, Burke joined the army and landed by choice in the hottest hot zone in the United States, the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Md. There, in the mid-1970s, he took charge of the institute’s vaccine clinic and its high containment suite, the kind of place that figures in every Hollywood version of germ-driven apocalypse. He donned a protective “space suit” when examining his patients, not knowing whether they suffered from a garden-variety flu or something far worse.

At the time, the U.S. Army ran the largest vaccine development program anywhere, and during his 23-year military career Burke traveled the globe, tracking, studying, and trying to contain emerging virus threats. He remembers, in particular, returning to the United States after a six-year assignment with the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand. It was the early 1980s, just as a disease catastrophe began to unfold. A mysterious condition was killing adults—mostly men—in their prime, and the deaths were on the rise. In 1983, scientists identified the human immunodeficiency virus, or HIV, as the cause of the deadly new syndrome that was crippling human immune systems—AIDS.

Burke became involved in HIV studies early on. Researchers in the department he led were the first to recognize the heterosexual transmission of HIV, previously thought to be spread only through homosexual contact or intravenous drug use. He personally designed and coordinated the testing of all incoming U.S. military recruits—up to 300,000 a year—for the virus. When the test results were completed, it was the first glimpse of HIV prevalence in a broad population. “I remember looking at the data and thinking, ‘Damn! This is what I’m going to be doing for a long time,’” Burke says.

On assignment for the army, he set up HIV testing centers around the world. Anytime there was a new area of HIV infection, he went there personally. In Zambia, he isolated the first HIV genotype in southern Africa. In Thailand, he was first to isolate HIV in Asia, as well. Over time, Burke and others realized that the AIDS pandemic was actually a series of sub-epidemics: the C-type in southern Africa, the B-type in North America and Europe, the E-type in southern Asia. But in central Africa, for inexplicable reasons, every type of HIV was present, including some mixed-type versions. Naturally, that’s where Burke wanted to be, and that’s what put him at a Cameroon ferry landing in the mid-1990s.

At that point, he had retired from the army with the rank of colonel and joined the Johns Hopkins Bloomberg School of Public Health, where he led a prominent vaccine research center and became known as one of the world’s foremost experts on emerging viruses.

Other researchers, too, were searching for clues to the origins of HIV. For years, scientists had known that nonhuman primates frequently carry various strains of benign retroviruses that never blossom into immune-system deficiencies. Even so, a direct link between such viruses in apes and humans had not been established.

But the AIDS epidemic stimulated research that revealed HIV to be remarkably adaptable. Each viral particle carries two complete copies of its own genetic material. When two or more particles infect the same cell, they can swap parts of their genetic makeup, creating new genetic forms of the virus. Conceivably, as this gene swapping evolves, a newly assembled gene sequence might suddenly match the genetic code of another species, making it possible for the virus to plug into another species’ gene blueprint. In fact, in the early 1990s, a research group at the University of Alabama at Birmingham had found evidence of a retrovirus crossing from one ape species to another.

“The question became,” says Burke, “was bush-meat-hunting the root of how HIV got into humans and, if so, could we find evidence that the gene pool of the viruses in humans was being enriched from the gene pool of the viruses in chimps and other monkeys? That would explain the high level of genetic diversity in the viruses in central Africa.”

Back in the laboratory, Burke’s research didn’t uncover direct evidence that HIV-type viruses were crossing species from apes to humans, but it did reveal that other viruses appeared to be making the leap. So, he began examining the genetics and characteristics of different types of viruses, looking for viruses that might be capable of crossing species into humans.

In a 1997 paper, Burke cited several of these viral candidates, including a type of contagion known as coronaviruses. Five years later, the SARS (severe acute respiratory syndrome) epidemic exploded suddenly in Asia. Its cause was a coronavirus, apparently transmitted to humans from infected civet cats sold in Asian food markets. Subsequent research by others suggested that the initial virus may have been carried by bats and somehow transmitted to cats, then humans.

In the years since Burke’s first visit to Cameroon, it has become apparent through the work of many researchers that viruses can indeed cross species. But scientists don’t yet know enough about how killer viruses emerge. “We have a poor understanding of viruses in the animal reservoir, the potential pools of threats,” Burke says. “It would be very worthwhile for us to have more intensive studies of viruses that are not yet causing diseases but could someday in the future. We need to get out and sample wildlife populations to get a real inventory of the viruses around the world today.”

According to Burke, the study of prior pandemics, like the 1918 “Spanish” flu, shows with certainty that global killer-flu pandemics originate when influenza virus genes from a bird species enter humans and then genetically adapt to make human-to-human transmission possible. At any given time he estimates that up to 20 percent of what appear to be healthy waterfowl may be infected with one or more types of bird flu. In a 2005 public health commentary, Burke wrote, “Every day, millions of billons of virus particles are silently replicating, swapping genes, mutating, and evolving in waterfowl. Occasionally, an otherwise mild avian influenza virus changes to become a highly pathogenic virus that can infect, kill, and start epidemics in domestic poultry.”

He targets the year 1997, when a particular type of bird flu emerged in Hong Kong that, for the first time, was able to make the leap to infect and cause illness in humans. Since then, that virus, H5N1, has infected more than 100 people, killing roughly half of those infected and capturing worldwide media attention. So far, the virus hasn’t been able to pass easily from person to person. At least, not yet. “Given that no humans are immune to the virus, virtually everyone on the
planet is at risk of becoming infected,” Burke wrote in 2005.

Theoretically, a vaccine could offer protection, but it would have to “nail” the genetics of the virus immediately, and the genetics are constantly evolving. Enough vaccine would need to be available to thwart the disease wherever it pops up regionally; and, to be effective, the vaccine would also have to be administered quickly, before the virus has a chance to spread. Even just a few months without a viable vaccine would allow the virus to spread globally and become a killer pandemic. Antiviral medicines are another possible solution, but Burke says they’re only useful to prevent infection during the 10 days they’re ingested. The timing would have to be perfect. And the total amount needed to protect a world population would be massive.

While at Johns Hopkins, Burke initiated pioneering computer simulations to predict and prepare for emerging epidemics, looking at the effects of vaccines, antiviral medicines, and even quarantines or “social distancing” as preventive measures. He has worked with social scientists and statistical physicists to develop models that create entire artificial populations, track how a potential epidemic like bird flu or smallpox would spread, and examine the effects that different responses would have. “A good bit of our U.S. national flu policies were guided by these models,” he notes.

Prediction and preparedness have long been key concepts for Burke. At one point during his Cameroon trip, the group’s land cruiser pulled up short to avoid hitting a massive tree that had fallen across the road during the previous night’s storm. No one in the vehicle had an ax, and Burke noticed one of his colleagues scanning the leafy tops of the surrounding trees. “What are you looking for?” Burke asked. His colleague replied, “A place to spend the night.” Facing the impending dusk and a night of tree-top accommodations in a remote and dangerous forest, Burke was reminded of the need to be equipped for any situation. But he didn’t spend the night nestled among high branches. Instead, the men looped a chain between the tree and the land cruiser and then pulled the rot-weakened trunk apart to clear the road.

To Burke, quick thinking and a chain are akin to the current protective measures against epidemics. What he’d prefer is comprehensive knowledge of weather storm patterns and a ready supply of axes. In other words, prediction and preparedness are as important as longer-term surveillance and response readiness.

“That’s the motivator,” Burke says. “What can we do to be smarter about where diseases emerge and how they are going to emerge? Can we spot them more quickly and have a rapid response to contain things before they get out of hand? If we don’t have enough vaccine or enough drugs, what do we do? The more prepared we are, and the earlier we respond, the better off we’re going to be. All you have to do is watch the inexorable trajectory toward 100 million AIDS cases to understand that’s probably not a bad idea.”

In its 2007 report, the World Health Organization (WHO) warns of the potential for millions of deaths from future epidemics. During the last five years, WHO tallied more than 1,100 epidemics around the globe. The frequency of widespread passenger travel in modern society only adds to the potential for virus-driven disaster.

Today, more than a decade after that Cameroon trip, Burke is dean of the University of Pittsburgh’s Graduate School of Public Health (GSPH), where he is expanding efforts and resources to protect humans against global disease epidemics.

“I was particularly impressed by the school’s strength as a research organization,” says Burke about his decision to come to Pitt in July 2006. “We’re third in the nation among public health schools in attracting funds from the National Institutes of Health (NIH). And, we’re ahead of Harvard, Johns Hopkins, Columbia, and other top competitors in receiving per-faculty research dollars from NIH.”

In addition to his GSPH dean’s role, he is Pitt’s associate vice chancellor for global health, a newly created position to coordinate all of the University’s international health activities. He also is the inaugural holder of the UPMC-Jonas Salk Chair in Global Health.

But it’s his role as director of Pitt’s new Center for Vaccine Research that may have the most far-reaching effects on infectious culprits like H5N1, the bird-flu virus that emerged in Hong Kong a few years ago. The center will develop, test, and produce vaccines against viruses that pose an existing or potential threat to large human populations. One current direction is vaccine development against dengue, influenza, and tuberculosis, which are all significant global health problems. In November, the center received $4.8 million in federal grants to develop a vaccine strategy against dengue fever, which infects tens of millions every year and can be fatal.

“The center’s work will be matched with international activities,” says Burke. “We will create computer models and simulations to decide what is the best kind of vaccine to make and then work with partners in the field to get it done.”

Burke also is looking beyond what Pitt already has to what it could potentially support. For instance, the University in partnership with a major pharmaceutical company could produce and distribute vaccines that are essential to saving lives anywhere in the world, even in the poorest global communities. As it stands now, many for-profit companies simply don’t pursue vaccine-development projects if the market won’t produce financial gains.

“Having the full range of capabilities here at Pitt—from vaccine development and testing to clinical trials to international studies to simulation to production—is an appealing vision,” Burke says. “The question is, ‘How fast can we approach that vision?’” Any day could bring the next avian flu, the next SARS, the next HIV.

Burke knows firsthand how suddenly, from seemingly nowhere, disease can strike. About a year after his trip to Cameroon, he began to feel an unquenchable itching in his skin. It soon became maddening. The diagnosis was river blindness, caused by a parasitic worm that enters the human bloodstream by the bite of a black fly—the same kind of black fly that he saw in droves at the ferry crossing. Burke received five years of treatment before he was cured.

He is sure he was somehow bitten that day at the river, despite his awareness of the threat and his steps to take every precaution. But sometimes, even the best preparation fails. Burke would say you have to be prepared for that, too.


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