The Viral Storm

by Nathan Wolfe

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  For our purposes, we’ll define a pandemic as a new infectious agent that has spread to individuals on all continents (with the exception, of course, of Antarctica). One may counter that it would theoretically take only a dozen or so infected people to accomplish this—a few infected people per continent. That may be true, but it would be exceptionally rare for a microbe to spread so widely and infect so few individuals. And if it did manage to occur, even with twelve people, it would still represent a potent risk to all of us.

  Defining precisely when a new spreading agent actually becomes a pandemic is less important for our objective here than understanding how pandemics are born. What I wanted to know when I began my research on pandemics was how something goes from being a strictly nonhuman infection to one spreading to humans on every continent.

  In 2007 I worked with the aforementioned polymath biologist and geographer Jared Diamond and the tropical medicine expert Claire Panosian to develop a five-step classification system for understanding how an infectious agent living exclusively in animals can become an agent that spreads globally in humans. The system moves stepwise from agents that infect only animals (Category One) to agents that exclusively infect humans (Category Five).

  Jared and I spent many afternoons pondering this process over extended writing sessions at his home in Los Angeles. During our lunch breaks, we’d stop writing to brainstorm, using thought experiments, how a virus might make this jump. We came up with one fairly elaborate idea centered around the Diamonds’ geriatric but much beloved pet rabbit, Baxter, and his invented disease—the dreaded Baxterpox. Even in our imaginary world, most human diseases have their start in animals.

  The five stages through which microbes of animals evolve to cause diseases confined to humans. (Nature / Nathan Wolfe, Jared Diamond, Claire Panosian)

  Few of us now live on or near farms; fewer still live as hunter-gatherers surviving on wild plants and animals. We live in worlds filled with buildings and streets, where the dominant and notable forms of life are basically ourselves. Despite living on every continent with a population of seven billion individuals, we still represent a very restricted segment of the biological diversity on our planet.

  As discussed in chapter 1, most of the diversity of life on our planet resides in the unseen world; in bacteria, archaea, and viruses. Despite our massive numbers and global reach, our human diversity pales in comparison. This is true even for our microbes. Most of the diversity in mammalian microbes resides in other animals, not humans. Some animals house greater microbial repertoires than others. For example, fruit bats are a notorious reservoir species. They often live in large colonies and are highly mobile “travelers” connecting multiple regions with high levels of biodiversity. On average a species of colonial fruit bat will have a greater diversity of microbes than, say, a two-toed sloth living a largely solitary life.

  However you cut it, there are estimated to be over five thousand species of mammals on the planet and only one species of human. The diversity of microbes that can infect us from other mammals has and will always be substantially greater than the diversity of microbes that already does infect us. That’s why we conceptualize the process as a pyramid, with the greatest diversity of microbes falling into Category One.

  We’ve seen that most of the microbes with the potential to cause new human pandemics live in animals. Domestic animals certainly represent a threat, but as discussed earlier, most of what they had to contribute to the human microbial repertoire has already jumped over. Right now, the threat from domestic animals comes more from them acting as bridges to allow the movement of wild animal microbes into the human population. Moreover, while the actual number of living domestic animals is quite high, they represent a small percentage of the diversity of mammals since we’ve only domesticated a small percentage of all animals. Clearly, when it comes to new pandemics, wild animals are where the action is.

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  When I lived in Malaysia during the 1990s conducting my doctoral research, I spent time working with the accomplished parasitologists Janet Cox and Balbir Singh. Janet and Bal devised creative ways to detect malaria in blood that had been dried on small pieces of laboratory filter paper (it looks like plain but thick white paper). This technique made it easier to do field screening or specimen collection in remote locations. Since blood could be dried easily and stored at room temperature, this method did away with the logistics of having to keep a specimen cold in regions without electricity. Janet and Bal taught me how to use these lab techniques, and, with their sweet kids, Jas and Serena (now both college students!), introduced me to the amazing Malaysian state of Kelantan.

  Kelantan is a small state on the border of Thailand that still adheres to Malaysian traditions that have disappeared in much of the now modern and economically booming country. Many of the people in Kelantan wear traditional Malaysian clothing, the official weekend is on Thursday and Friday, and there’s not a drop of alcohol to drink (at least officially) in the majority of the state. The pace of life in Kelantan is more relaxed than almost anywhere I’ve visited in the now bustling, dynamic countries of Southeast Asia.

  Among the fascinating sights to see in Kelantan was one that held particular scientific interest to Bal, Jan, and me—coconut-picking macaques. In a unique practice, some coconut farmers in northern Malaysia and southern Thailand work with pig-tailed macaques, a species of Southeast Asian monkey, trained to climb palms and harvest coconuts. A well-trained animal can pick up to fifty coconuts an hour—quite an efficient farmhand.

  One evening after dinner at their house, Bal told us of a report he’d heard of a man with a particularly devastating neurological disease, the symptoms of which suggested it was caused by a virus or other infectious agent. This man worked with the curious coconut-picking macaques.

  The close and long-term relationship between macaques and their human handlers presented an ideal chance to study the first and second stages of the classification system I’d developed with Jared and Claire. We could study the microbes present in the animals and monitor them for any cross-species jumps into humans. Among the more interesting targets of our investigation would be the deadly herpes B virus.

  Herpes B may not sound as if it should be particularly dreaded, but it’s among the deadliest viruses a human can contract. Amazingly, the virus is almost completely benign among the macaques that sustain it. For the coconut-picking macaques, herpes B virus is just like herpes simplex is for a human, creating minor lesions that spread the virus through intimate contact like a bite or sex. Inconvenient for these monkeys, perhaps, but certainly not deadly. Yet when the virus crosses into humans, it causes severe neurological symptoms and invariably results in death. Transmission of the virus has been documented in a number of primate handlers in the West, including a sad case of a young woman working at the Yerkes Regional Primate Research Center in Atlanta who became infected after a captive macaque spit in her eye. At the time, no one had documented the infection occurring among the Kelantan coconut harvesters, despite the fact that they work with these animals daily and with far fewer protective measures in place.

  For Bal, Janet, and me, studying the Kelantanese macaques and their handlers provided an interesting way to monitor the entry of these viruses into human populations and to witness the first step in the process of how potential pandemics are born. Yet, as with the case of rabies in young Jeremy Watkins, we did not expect to see these herpes B viruses go anywhere outside Category Two. They would remain as infections that had made the leap but didn’t have the potential to spread in humans. While the victims might die from infection, the people infected by these monkeys would never go on to spread the virus to their families or others. Thus, no pandemic for herpes B. For that, we’d need a different kind of virus.

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  The interface we have with the animals in our world leads to a constant flow of microbes. Every day, millions of people are exposed to animal microbes. Some rare infections
lead to death. Much more frequently, they are transient and benign infections, such as a bacteria from a pet dog or cat. The vast majority of these Category Two viral jumps represent dead ends from the perspective of a microbe: they infect a single individual, and that’s that.

  Sometimes, though, something unusual happens that is potentially pivotal for our species: a microbe that jumps over may have the capacity to move from one human to another human. If a microbe accomplishes this, it moves to a Category Three and toward becoming a pandemic.

  In late August, 2007 information began to trickle in to health authorities on an unidentified illness in a remote area of the Kasai-Occidental Providence in the Democratic Republic of Congo. The outbreak was centered around Luebo, a town of some historical importance as the last point that early twentieth-century steamers could navigate to on the Lua Lua River. The case reports listed a number of bad symptoms—fever, severe headache, vomiting, major abdominal pain, bloody diarrhea, and severe dehydration. The first recognized cases were on June 8, following the funerals of two village chiefs. Tellingly, the entire first group of individuals infected had assisted with the burials.

  The symptoms and the connection to burials led the Congolese health authorities to consider the possibility of Ebola, a virus that spreads through direct contact with blood and body fluids, and they responded accordingly. The head of the Congolese team was Jean-Jacques Muyembe. Jean-Jacques is a professor and the director of the national biomedical research institute, the INRB. His bright laugh and mild-mannered demeanor belie the fact that he’s had more experience dealing with viral hemorrhagic fevers4 than perhaps any other single person in the world. I have fond memories of working with Jean-Jacques in a remote location in central DRC and watching him break into hysterics as he watched me devour a meal of pan-fried grub worms for dinner.

  Jean-Jacques and his team called in long-standing collaborators, including Eric Leroy, a crack virologist who runs the only high containment bio-safety level four laboratory in central Africa that is capable of studying the world’s deadliest viruses. Leroy, Muyembe, and colleagues at the CDC and from other groups like Médecines Sans Frontières (MSF) worked to contain the Luebo outbreak. They sequenced a small portion of the virus’s genetic information and discovered that it was, in fact, the Ebola virus.

  Ebola hemorrhagic fever strikes fear in the hearts of people in the DRC and throughout the world. The Ebola virus kills quickly and dramatically. It also spreads. While the exact number of cases will never be known, the Luebo outbreak of 2007 probably infected around four hundred people. All of them were infected from a single virus that jumped from an animal into the first human victim and then subsequently spread. Around two-thirds of them died.

  Part of the public fascination with Ebola relates to how little we know about something so deadly. The truth is that it largely remains a devastating and unsolved mystery.

  What we do know about the Ebola virus is that it appears occasionally in humans. We know that it can enter into humans from multiple animal species. Leroy and his colleagues have identified the Ebola virus in a few species of bats, helping to pinpoint them as the likely reservoir. A range of studies also documents how Ebola affects gorillas, chimpanzees, and some species of forest antelope. We know that for now it’s a Category Three microbe on the route to pandemics: it can infect and spread in humans, although not to the point of sustained transmission. Effectively, it’s a virus with potential for localized outbreaks.

  Together with Leroy and his colleagues, we looked in detail at the virus that caused the Luebo outbreak of 2007, as well as a smaller outbreak that occurred about a year later in December 2008 in exactly the same region of DRC. We found that the viruses that caused the two outbreaks were nearly identical and formed an entirely new type in the deadliest group of the Ebola viruses: the Zaire group.

  That the Luebo outbreaks came from a new variant virus was significant. It meant that the depth of the genetic pool of viruses that could jump to us from animals was greater than we’d imagined. Now we understood that new versions of the Ebola virus had the potential to enter into humans, perhaps someone who hunted or butchered the meat of wild fruit bats. This meant that we probably haven’t seen everything that the Ebola virus can serve up. For now, we classify Ebola as a Category Three agent, but our finding suggests that there are more undiscovered variants of Ebola out there that can cross into us. It’s possible that a distinct and as yet unknown Ebola virus circulating in animals might have the potential to spread more broadly than any Ebola in the past.

  Does the Ebola virus have the right stuff? Could it move higher in our pyramid classification system? From the perspective of a pandemic, all of the Ebola hemorrhagic fever outbreaks to date have been stillborn. They spread, but lucky for us, that spread remains limited.

  Unlike the casual contact or airborne transmission of influenza, the majority of cases in the Ebola hemorrhagic fever outbreaks that have been studied resulted from intimate contact with the blood and body fluids of a very sick person. Generally, people become infected when preparing a previous victim for burial or when caring for the sick. Limited transmission makes broader, sustained spread less likely.

  There are other disadvantages that the Ebola virus has in the microbial race to become a pandemic. The incredibly nasty symptoms of Ebola are both very specific and also coincide with its capacity to spread. Since few other viruses cause the dramatic symptoms of Ebola, it can be identified relatively quickly and the sick individuals can be isolated. Since it’s the very sick people who spread the virus, isolation works to stop it. This is the approach that organizations like the CDC and MSF use to quell Ebola outbreaks: get in, isolate victims, stop contact with blood and body fluids. For the Ebola viruses that have emerged to date, it’s a strategy that works. This kind of strategy often fails with more nimble viruses.

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  In 1996 and 1997 quite another sort of outbreak occurred in the DRC. This outbreak lasted over a year, and while estimates vary, it likely hit over five hundred people. Like Ebola hemorrhagic fever, the cases began with fever, aches, and malaise. After a few days, rather than the bleeding characteristic of Ebola, patients developed a severe rash consisting of pustules all over the body, often first appearing on the face. The symptoms looked quite a bit like smallpox, perhaps the greatest scourge of human history. But that was impossible. Smallpox had been eradicated nearly twenty years earlier.

  The cause of this outbreak was not smallpox, but it was a virus in the same group of viruses (the Orthopoxvirus genus) called monkeypox. Monkeypox has probably affected humans for ages, but it was only first recognized in 1970 during the smallpox eradication effort. Prior to that, any monkeypox cases were likely misdiagnosed as smallpox. While the ultimate animal reservoir for monkeypox remains unknown, it’s almost certainly not a monkey, but rather a squirrel or other rodent. Because the virus can infect species of nonhuman primate, occasional human cases can result following contact with an infected monkey, hence the misnomer.

  A young man with monkeypox. (Lynn Johnson / National Geographic / Getty Images)

  I’ve been working on monkeypox since 2005 with Anne Rimoin, an epidemiologist from UCLA, and her colleagues in the DRC, including Jean-Jacques Muyembe. Annie’s spent much of the last ten years pushing deeper into the logistical nightmare of conducting high-quality surveillance for novel diseases like monkeypox in some of the most rural regions in the world. She manages to do it with flare. I’ve seen her touch up her eyeliner in the mirror of an off-road motorbike in a rural town in central DRC.

  In 2007 we reported that monkeypox does not simply appear in outbreaks. The long-term work Annie and her colleagues did showed us that the virus should probably be considered endemic among humans—it is a permanent part of our world. Rather than follow the traditional method for investigating monkeypox outbreaks, Annie and her team set up shop in regions that had known infections. Through constant monitoring, it became clear that there were monkeypox cases all year
long. And the number of cases was growing.

  Dr. Anne Rimoin in DRC. (Prime Mulembakani)

  In the final analysis it was just a matter of how hard you looked. During my visits to these sites, I’ve always seen cases of monkeypox. Some of these cases were the result of exposure to infected animals, but a number of them were the result of person-to-person transmission, the hallmark of a virus that’s beginning to fully transition to a new host species.

  You might wonder how such frightening cases of monkeypox could exist without the world being aware of them. The answer is that the region where we conducted this work is among the most remote in the world. Just to get to this area requires a chartered flight on a small plane or a three-week boat trip on tributaries of the Congo River that are only navigable during the rainy season. The setting is austere and beautiful, with very few roads. Most villages are linked together by simple footpaths. The research uses rugged off-road motorbikes traveling sometimes for as long as ten hours to get to the site of a case. Just dodging the chickens and pigs represents a major challenge.

  Despite the incredible dedication and skill of our Congolese colleagues, the idea that the current meager resources devoted to health in the DRC could permit full coverage of a country four times the size of France is crazy. Yet this is one of the most important places in the world for the emergence of new viruses. Without a doubt, an interconnected world that doesn’t invest in the infrastructure needed to monitor these viruses is doomed to fall victim to more epidemics.

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  Whether or not monkeypox has the potential to join the pantheon of our Category Four agents remains to be seen. Microbes that reach Category Four can live exclusively in humans while simultaneously continuing to live in animal reservoirs. Microbes in Category Four include dengue, discussed in chapter 4. Dengue maintains itself in human populations but also persists in a forest cycle spread by mosquitos among nonhuman primates.