The Viral Storm

by Nathan Wolfe

  Over the following months there were a total of ninety-three human cases of monkeypox in six midwestern states and New Jersey. And while most of them probably resulted from direct contact with infected prairie dogs, some may very well have resulted from human-to-human transmission.

  * * *

  The moving and mingling of animals as pets and food increases the probability that new agents will enter into the human population. It also increases the chances that distinct microbes will end up in the same host and exchange genes. As discussed earlier, there are multiple ways in which a virus can change genetically: direct changes in genetic information (mutation) or the exchange of genetic information (recombination and reassortment). The first option, genetic mutation, provides an important mechanism for slow and steady production of genetic novelty. The second options, genetic recombination and reassortment, provide viruses with the capacity to quickly gain entirely novel genetic identities. When two viruses infect the same host, they have the potential to recombine, exchanging genetic information and possibly creating a completely new “mosaic” agent.

  This has already occurred to important effect. As we learned in chapter 2, HIV itself represents a mosaic virus—two monkey viruses, which at some point infected a single chimpanzee, recombined and became the ancestral form of HIV. Similarly, influenza viruses have the capacity to pick up entirely new groups of genes by forming these mosaics through reassortment, where entire genes are swapped.

  Influenza viruses can reassort on the farms where humans, pigs, and birds interact. Pigs have the potential to acquire some human influenza viruses. They also can acquire viruses from birds, including wild birds that may pass through on migration routes. These wild birds can infect pigs directly or indirectly through domestic birds such as chickens and ducks. When new viruses from birds interact with human viruses in an animal such as a pig, one of the outcomes is a completely new influenza virus with some parts from the circulating human virus and some parts from the bird virus. These new viruses can spread dramatically when reintroduced into human beings since they can differ sufficiently to avoid detection by natural antibodies and vaccines from earlier circulating influenza strains.

  Recombination plays a potentially vital role in a number of viruses. Genetic analyses of SARS show that it’s likely a recombinant virus between a bat coronavirus and another virus, probably a separate bat virus we have yet to discover. These two viruses formed a novel recombinant mosaic virus prior to infecting humans and civets. These viruses’ potential to recombine may very well have related to the interaction of animals that previously would never have been in contact in the wild, as they made their way along market networks.

  My mentor Don Burke, who now leads the University of Pittsburgh’s School of Public Health, has played a pivotal role in pointing out how recombination between viruses can help seed new epidemics. He coined the term emerging genes to refer to this process. Historically, virologists thought that new epidemics result from the movement of an entire microbe from an animal to a human. As we’ve seen in HIV, influenza, and SARS, recombination and reassortment provide other more stealthy methods to seed new epidemics. Rather than transplant an entire new microbe, two microbes, one old and one new, can temporarily interact in a single host and exchange genetic material. The resulting modified agent may have the potential to spread and become a completely new, and completely unprepared for, pandemic. In these cases it’s actually newly swapped genetic infomation that causes the pandemic rather than a new microbe—hence the term emerging genes.

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  In the coming years we’ll see more and more pandemic threats. New infectious agents will spread and cause disease. New pandemics will emerge as we go deeper into the rain forests and unleash the agents previously unconnected to international transportation networks. These agents will spread as dense population centers, local culinary practices, and wild-animal trade increasingly intersect. The impact of epidemics will be augmented by HIV-caused immunosuppression that increases the risk of new agents adapting to a damaged human species. As we move animals quickly and efficiently around the world, they will, in turn, seed new epidemics. Microbes that have never encountered each other now will, and they’ll form new mosaic agents capable of spreading in ways that neither of their parents could manage. In short, we’ll experience a wave of new epidemics, ones that will devastate us if we don’t learn to better anticipate and control them.

  PART III

  THE FORECAST

  9

  VIRUS HUNTERS

  On December 9, 2004, primatologists working in the Dja Biosphere Reserve in southern Cameroon collected specimens from a dead chimpanzee. The chimp was sprawled out on the forest floor, eyes closed, but seemingly unmolested by a human or other predator. The team was rightfully concerned.

  Belgian scientist Isra Deblauwe and her Cameroonian colleagues had started their long, tedious work some three years earlier. In the tradition of primatologists like Jane Goodall, their goal was to study wild great apes, our closest living relatives, to learn about them and ourselves.

  And a few years later, they produced some interesting results. The team reported that, like other chimpanzee populations, the chimpanzees in the Dja used tools. In particular, they modified sticks to extract honey from underground bee nests. Chimpanzees, like all apes, including ourselves, love honey, and the information from the Dja team would add to the understanding of how different chimpanzee cultures use tools in different ways.

  But on that rainy December day in 2004, honey was the last thing on the scientists’ minds. Four days after taking samples from the first dead chimpanzee, they took samples from another. Then on December 19 they took samples from a dead gorilla. This was worrying. Since the primatologists only followed a fraction of the population of apes in the Dja, what they’d seen was likely to be just the beginning. Many other unidentified apes might be dead, valuable wild kin whom the team had spent years working to understand. The consequences for conservation and research could be considerable.

  But the threat to wild apes, while significant, was not the only problem. The researchers knew that the Ebola virus had wiped out large numbers of apes in Gabon, only a few hundred kilometers to the south. Ebola not only kills chimpanzees but from time to time has also jumped to humans causing dramatic and potentially epidemic-inducing cases. They also knew that one of their primatologist colleagues had acquired Ebola in the Ivory Coast when investigating deaths just like these. Whatever caused these ape deaths was not to be taken lightly.

  Fortunately, they had responded according to a plan. First and foremost, the primatologists knew that they should not directly touch the carcasses. Months earlier, when the first dead animals had been seen, they had sent a message to colleagues in Yaoundé, Cameroon’s capital. The message in turn was transmitted to Mat LeBreton, the dedicated and skilled biologist who leads our ecology team and has pioneered a number of new techniques in viral ecology. Based in Yaoundé, LeBreton helped support an international team, including relevant ministries and laboratories in central Africa and Germany on the outbreak investigation that would follow.

  The investigating team rapidly put together and deployed a mission to the Dja, a stunningly beautiful and unique rain forest habitat located along one of the major tributaries of the massive Congo River. There they worked with the primatologists to collect the specimens. They managed to obtain specimens from the skull and shoulder of the first chimpanzee. They also collected a specimen from the leg of the second chimpanzee, the jaw of the gorilla, and some muscle from a fourth victim—a chimpanzee—who died in early January 2005.

  The safely preserved specimens then made the trip to expert laboratories. They went to the high containment laboratory of Eric Leroy, the virologist whom we worked with to discover the new strain of the Ebola virus discussed in chapter 5. The specimens also went to our collaborator Fabian Leendertz, a veterinarian and microbiologist working at the Robert Koch Institute in Germany who has perfected the st
udy of ape microbes during many years spent shuttling between field sites in Africa and his lab in Berlin.

  The results were surprising. While we all had come to assume that the same wave of Ebola knocking down ape populations south of the border in Gabon had killed the animals in the Dja, the specimens all came back negative for the Ebola virus. They were, however, all positive for another deadly agent—anthrax.

  In 2004 Leendertz and his colleagues had reported a similar die-off of chimpanzees in the Taï forest of the Ivory Coast due to anthrax. So while the gorilla death in the Dja was the first of its kind, anthrax was already known to be a killer of forest apes. Strange perhaps but not unprecedented. How exactly a bacteria normally found in grasslands ruminants got to the apes in the Dja and Taï forests is still a mystery. There were some theories. Anthrax spores remain viable for long periods of time, even up to a hundred years. The spores can contaminate water supplies, so the apes may have picked it up from lakes or creeks. They may also have become infected while hunting or scavenging on ruminants, such as forest antelopes, that had themselves been infected. Or perhaps, at least in the Taï forest outbreak, neighboring farms had seeded the outbreak when the apes had foraged for food in cropland contaminated by anthrax from cattle.

  Whatever the route of infection, the findings from the Dja and from the earlier animal epidemic in the Ivory Coast showed that the declining populations of African apes had more than hunting and habitat loss to blame. Viruses like Ebola have swept through large swaths of the remaining habitats of wild apes, and now anthrax must also be considered a threat to these valuable wild animals. From a personal perspective, having worked with wild chimpanzees and helped habituate populations of gorillas in Uganda, I feel that the mounting threats to our closest living relatives is a tragic loss to the heritage of our particular form of life.

  Gorilla killed by anthrax in the Dja Biosphere Reserve, Cameroon. (Matthew LeBreton)

  From the perspective of my work tracking and preventing pandemics, the deaths pointed out another glaring weakness in the way that we catch these epidemics. The discovery of anthrax in the Dja forest did not represent a success in pandemic prevention. It was rather the epidemiological equivalent of dumb luck. Only a trivial fraction of the global ape populations are under the watchful eye of woefully underfunded primatologists. If we’re relying on these scientists to regularly capture the animal epidemics that could signal future human plagues, then we’re destined to fail. To truly catch epidemics early, we’ll need much more.

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  How can we hunt down deadly viruses and control them? A few primatologists finding dead animals is not a surveillance system. But what is the right way to catch new epidemics and stop them before they spread? This section will explore just that: the contemporary science of pandemic prevention. It will discuss the ways that my team and other colleagues and collaborators are working to create systems that will be able to catch and stop new epidemics before you (or CNN) even know about them. Preventing pandemics is a bold idea, yet no bolder than when cardiologists in the 1960s began to think that they could prevent heart attacks, a medical advance that was radical at the time but is now largely taken for granted.

  My own thinking on this dates to the late 1990s when I joined Don Burke at Johns Hopkins and agreed to establish a field site aimed at monitoring humans and animals for new viruses in central Africa. It was an exciting time, when the idea that simply responding to pandemics would no longer be sufficient was truly in the air. I remember spending many afternoons in Don’s office alternating between urgent scribbling on the whiteboard and thinking out loud about what would be needed to accomplish the task.

  Among the ideas that we generated during that time, one lasting concept particularly stands out: viral chatter. When he coined the term, Don did so as a direct parallel to intelligence chatter. One way of thinking about this is to ask the question: how do security services prevent terror events?

  Intelligence services use a range of techniques to monitor for potentially threatening events, but among their most valuable tools is the monitoring of chatter. Intelligence agencies scanning e-mails, phone calls, and online chat rooms can follow the frequency that certain signals occur. If a journalist were to fire off an e-mail that included the words al-Quaeda and bomb for example, it would be picked up by an automated system that filters for suspicious key words. Having said that, it would not likely make it to the desk of an analyst, since the systems also register e-mail accounts and IP addresses and would hopefully flag the chatter with journalist.

  During testimony on the September 2001 attacks on the United States, the former CIA director George Tenet said that the “system was blinking red” in the months leading up to 9/11. Similarly, although it was an accidental event, the day that the Chernobyl reactor melted down in 1986 there was a significant spike in message traffic in the former Soviet Union. Knowing what sorts of key words to look for and who the usual suspects are, as well as understanding how they communicate with each other can provide valuable intelligence to help predict rare but important events.

  As Don and I considered it, we asked ourselves what a global system to monitor the viral equivalent of such chatter would look like. How could we monitor the many thousands of interactions that occur between humans and animals in order to detect the chatter events—in our case the jumping of novel viruses to humans—that would signal a looming plague?

  Clearly, a system that depended on communities like the primatologists, whose primary focus was studying animal behavior and ecology, would not be sufficient. An ideal system would monitor global viral diversity in humans and animal populations and detect when agents jumped from animals to humans. While theoretically possible, such a system defied resources and technology at the time.

  As we’ll discuss in greater detail in chapter 10, the current laboratory methods for accurate and comprehensive surveys of the diversity of viruses in people and animals, while improving all the time, are not yet at the point of being deployed globally. Also, the simple logistics of monitoring everyone would be impossible. To begin, we’d need a much more focused system—a system focused on a small set of sentinels, key populations that would allow us to monitor viral chatter with the resources we currently have.

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  I remember vividly the first time I thought about the role of hunting in the transmission of infectious agents. While a graduate student at Harvard, I spent my first two years focused on the study of wild ape populations. Among the pleasures of being a graduate student in the Department of Biological Anthropology was being able to interact with one of the leading professors, Irv DeVore. Irv, a leading teacher and thinker in primatology and human evolution, has a striking head of white hair and a Vandyke beard to match. The son of a Texan Baptist minister, he taught human evolution with the fervor of an evangelist and is beloved among the scores of prominent scientists who benefitted from his tutelage.

  Dr. Irv DeVore during pioneering work to study wild baboons in Kenya. (Nancy DeVore)

  From 1993 through 1995 I worked for Irv as a teaching fellow for the class he co-taught at the time with the Harvard psychologist Marc Hauser. The course, Human Behavioral Biology, was referred to as “Sex” by the Harvard undergraduates because of the focus on human reproduction. During those years, I had the opportunity to meet with Irv in his office on the top floor of the Peabody Museum and on occasion at the wonderful evolution-soaked beer hours that proliferated at faculty homes.

  On one particularly memorable afternoon, I remember speaking to Irv in his wood-paneled office in the Peabody. During our freewheeling conversation, the topic reverted to my growing obsession at the time—microbes. It was then that Irv told me a story that would help put me on the research track I’ve taken for the last fifteen years.

  During one of his summers spent on Martha’s Vineyard, Irv had come across a dead rabbit while driving home. Assuming it was a healthy animal that had been killed by a car and being a lifelong hunter who had work
ed with indigenous hunters throughout the world, Irv did what seemed natural for him. He picked up the rabbit and brought it home, where he subsequently dressed and cooked it for supper.

  Within a few days Irv was very ill. He experienced fever, diminished appetite, and severe exhaustion. His lymph nodes enlarged. Fortunately, he went to an emergency room immediately, because as it turned out he’d acquired tularemia, a potentially fatal bacteria that often infects wild rabbits and other rodents. Death occurs in less than 1 percent of people with prompt treatment, but had he not been treated quickly, he may very well have died a painful death from multiple organ failure.

  Irv likely acquired tularemia when skinning the infected rabbit. A common route of entry for this bug occurs during butchering, when the bacteria can be inhaled into the lungs. By the time Irv finished his story, my mind was racing with the possibilities. One of Irv’s earlier works was a book called Man the Hunter, and he’d spent many years living with hunter-gatherer populations in Africa, populations that don’t practice farming and live exclusively on wild foods. Our conversation veered to the idea of working with these populations, who no doubt had extraordinarily high rates of exposure to the microbes in the animals around them.

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  In 1998, a few years after my conversation with Irv, I wrote about the role of hunting in disease transmission. In the article, I proposed that hunters could act as sentinels—and if we studied them over time we could get a sense of what, how, and when microbes were jumping into humans. During my conversations with Don Burke a few years later, this became a common point of discussion for us as we explored the concept of viral chatter. How might hunters lead us to the critical microbes making that fateful jump into the human species?