The Viral Storm (24 page)

Hunter carrying his bushmeat, Cameroon.
(
Nathan Wolfe
)

As we pushed forward with our work to characterize the diversity of HIV among these rural hunting communities, we also began what would become a main focus of my work over the past ten years—to discover completely novel viruses jumping into these highly exposed peoples. To do so, we approached one of the world’s top laboratory teams for discovering novel retroviruses, the broader family of viruses that includes HIV—the CDC’s Retrovirology Branch.

The CDC team included Tom Folks and Walid Heneine, two of the world’s leaders in retrovirology, but the person I’d spend most of my time working with was Bill Switzer. Bill has a youthful appearance that belies his actual age and a mellow demeanor that masks his relentless drive to chart the evolution of some of the most interesting viruses of our time. Whether face-to-face or by phone, Bill and I would spend the next ten years working together on an almost daily basis to assess what viruses besides HIV had jumped into those hunting populations.

My first major discovery with Bill was of an ominously named virus, the simian foamy virus (SFV). SFV received its name because of the way it kills cells. When you look at a culture infected with the virus, the cells die and bubble up, leading to a foamy appearance under a microscope. It’s a virus that infects virtually all nonhuman primates. And since each primate has its own particular version of the virus, it provides a great model for comparison. By sequencing the viruses, if we were then to find one in humans we’d know exactly what animal it had come from.

Interestingly, humans have no indigenous foamy virus. Bill and his colleagues showed some years ago that foamy virus has the unusual feature among viruses of cospeciation. In other words, the common ancestor of all living primates some seventy million years ago had a foamy virus, and as the various branches of the primate tree speciated over time, the virus passed along. The amazing result is that the evolutionary tree of foamy viruses and the evolutionary tree of primates are virtually identical. SFV may very well have been one of the viruses we lost during the pathogen bottleneck discussed in chapter 3.

When Bill and I and our colleagues started the work with primate foamy viruses we already knew that they could theoretically infect humans, as a few lab workers had previously acquired the virus. But we had no idea if this occurred under natural settings. We were surprised and quite excited to find that it did. I remember well the exact day it became clear. We were working together in Bill’s lab, and I went downstairs to get the images of a lab test called the Western blot, which shows whether or not individuals have produced antibodies against, in this case, the simian foamy virus. Bill came down that day to help me interpret the images. As soon as we saw the results, it was obvious that some of our study participants had been infected. I remember Bill and I looking at each other with equal parts shock and excitement. In a tangible way the work over the past years changed dramatically at that moment. To this day I have a framed copy of the Western blot on my wall.

Western blot showing the first evidence of antibodies against simian foamy virus in hunters.
(
Nathan Wolfe
)

On the one hand, there was relief—the research had succeeded. But there was also a sense of foreboding for us—retroviruses, viruses from the class that had produced HIV, were crossing into humans. And if we were seeing it within the first few hundred hunters we’d studied, it was by no means rare.

Over the coming months we saw that in fact a number of the people in our study who had reported hunting and butchering nonhuman primates had been exposed to SFV. More amazingly, some of the exposures had gone on to become long-lasting infections. After finding evidence that these individuals produced antibodies to the virus, we tried to obtain actual SFV genetic sequence, and what we saw surprised us. We found multiple people who were infected with strains of SFV from primates, ranging from the DeBrazza’s guenon, a small leaf-eating monkey, to the massive lowland gorilla. To our great satisfaction, we found that the results of our behavioral surveys matched. The gorilla SFV, for example, came from a man who had reported hunting and butchering gorilla meat. While many of the people in our survey had exposure to primates, few participated in the dangerous and highly specialized hunting of gorillas. The link was a smoking gun—the gorilla hunter had acquired the virus while hunting or butchering his prey.

The finding provided both a sense of adulation and fear. Most virologists would be lying if they said they didn’t enjoy finding something completely new. It had taken us years of hard work to line up the funding, find the local collaborating scientists who knew how to accomplish the work, set up a lab in central Africa, establish village outreach, collect specimens, store and ship them through the complexities of international agreements, and conduct the complicated laboratory work necessary to find an actual virus. The results showed that our system worked and that we were right in guessing that high levels of exposure to animals would lead to infection with novel viruses. Yet, the first evidence that new retroviruses were moving into humans also suggested that people’s faith in the existing public health structures—that they would inform us when novel viruses were moving into humans—was misguided. We were only beginning to see just how misguided it was.

In the following year, we went on to study yet another group of retroviruses, the T-lymphotropic viruses (TLVs). SFV was a virus with no real human precedents. Before our work, only a handful of laboratory workers had been infected, so determining how much the virus was likely to spread and cause disease—and its potential to become a pandemic—was unclear. Not so for the TLVs. It’s long been known that humans around the world are infected with two different varieties of TLV—HTLV-1 and HTLV-2; in fact, some twenty million people have these viruses. While some individuals can be infected without disease, many get sick from illnesses ranging from leukemia to paralysis. These viruses have pandemic potential. Clearly, if completely novel TLVs were moving from animals to humans, public health officials should know about it. Our results from SFV suggested this was a real possibility.

Going into the study, Bill and I knew that each of the two varieties of human TLV came from primates—just as HIV had. We also knew that another group of TLVs existed in primates that hadn’t yet been found in humans—the Simian T-lymphotropic Virus 3, known as STLV-3—so we began there. We screened the samples carefully, and as predicted, we found it—a virus infecting human hunters that was clearly unlike HTLV-1 and HTLV-2 and fell squarely with the viruses in the STLV-3 group. This was an important scientific finding for us. STLV-3 had the potential to cross into humans and was on the move. Even more surprising was an entirely new human TLV found in a single individual from eastern Cameroon—a virus we called HTLV-4.

The combination of finding a number of new SFVs in people exposed to primate bushmeat in central Africa and two entirely novel TLVs in the same population changed the way that we thought about our work. While it was theoretically clear that people exposed to a wide range of wildlife would acquire microbes from these animals, we didn’t know at the start whether monitoring those populations was practical or what such a system would look like. As we began the long and plodding work to determine the extent to which the new SFVs and TLVs were spreading and causing disease (work that continues to this day), our thinking opened up. We began to seriously consider that monitoring people highly exposed to wildlife could be a globally deployed system to capture viral chatter.

*   *   *

In 2005 I took a long shot. I applied to an unusual program sponsored by the National Institutes of Health (NIH), the largest government funder of biomedical research in the world. The NIH had supported my work in the past, but the world-class institution didn’t perfectly match the work I hoped to do in the future. While the NIH has a broad ranging program, it does not distribute its resources evenly. The NIH specializes in funding laboratory research rather than field research. It focuses its energy largely on research in more reductionist cell biology—work that focuses on very clear hypotheses that provide very clear yes or no answers. A program to spearhead a brand-new global monitoring effort to chart viral chatter and control pandemics was not something that would normally be supported. Yet in 2004 the NIH began a completely new program—the NIH Director’s Pioneer Award Program—aimed at sponsoring innovative research not normally supported by the NIH mission. The program gave grantees $2.5 million and five years to do largely whatever they felt was necessary to advance their scientific objectives. In the fall of 2005 I was among the fortunate individuals to get the award.

At this point, the pieces were beginning to fall into place. Certainly $2.5 million was nowhere near what would be needed to roll out a global monitoring system, but it was a good start. It allowed me to begin truly thinking about which key viral hotspots around the world needed the most urgent monitoring. Some key regions came to mind right away. The work with Jared Diamond and Claire Panosian had shown that Africa and Asia provided the lion’s share of our major infectious diseases. Those would be the places to start.

In the coming years, along with my team and a stunning range of local collaborators, I would take the model we’d developed in Cameroon and begin to deploy it in a number of other countries in central Africa. With the help of dedicated field scientists like Corina Monagin, who has become expert at making field sites in sensitive and difficult areas function, I’d renew collaborations from my years in Malaysia and begin to work with new sets of colleagues to establish programs in China and Southeast Asia. We’d set up the beginnings of a system to capture global viral chatter. Along with a growing number of colleagues worldwide, we would push ourselves to ask how we could best find new viruses. How could we capture a much higher percentage of the new viruses killing humans and infecting animals?

In the coming chapters, we’ll explore the results of this work. I’ll also discuss some of the cutting-edge tools employed to improve our ability to detect pandemics before they spread. While the threats associated with pandemics are large and growing, so too are the approaches and technologies to address them.

10

MICROBE FORECASTING

It was a large city. And it was hit hard. The first cases emerged in late August, and the victims suffered terribly. The earliest symptoms were profuse diarrhea and vomiting. They experienced severe dehydration, increased heart rate, muscle cramps, restlessness, severe thirst, and the loss of skin elasticity. Some of the cases progressed to kidney failure, while others led to coma or shock. Many of those who came down with the disease died.

Then on the night of August 31, the outbreak truly broke. Over the next three days, 127 people in a single neighborhood died. And by September 10 the number of fatalities would reach 500. The epidemic seemed to spare no one. Children and adults alike were killed. Few families did not have at least one member who came down with the disease.

The epidemic led to intense panic. Within a week, three-quarters of the neighborhood’s residents fled. Stores closed. Homes were locked. And you could walk down a formerly bustling urban street without seeing a single person.

Early in the outbreak, a forty-year-old epidemiologist began an investigation to determine its source. He consulted community leaders and methodically interviewed families of the victims and made careful maps of every single case. Following his hunch about a waterborne disease, he studied the sources of the community’s water and determined that it came from only one of two urban water utilities. He conducted microscopic and chemical analyses of specimens from the water system, which proved inconclusive.

In his report to the responsible officials, he presented his analysis and concluded that contaminated water was to blame. Despite the lack of definitive results from the analyses, the mapping of cases strongly supported his conclusion that one particular water outlet was the source of the outbreak. He recommended shutting down the water supply, and the officials agreed. And while the outbreak may have already been in decline because of the mass exodus, that investigation and water closure proved pivotal.