Array Sampson slings a makeshift shotgun over his shoulder and sets off down a footpath leading away from Okoroba, a remote village in Cameroon's Southwest Province. The lanky 36-year-old hunter is wearing ankle-length pants and slotted plastic shoes. He has a shaved head and a thin mustache, and his long strides carry him quickly past small stands of cacao trees and into the thick forest that blankets the surrounding hills. Expecting a half-day's hunt, he travels light: In addition to the shotgun, he carries only two shells, a small cane backpack, and a machete that hangs in a sheath from his neck. Fleetness could make the difference between a feast of monkey or antelope—bushmeat, as such forest quarry is known in central Africa—and a meager dinner for his family. Trailing behind Sampson, in slacks and an untucked polo shirt, is Efuet Simon Akem, a graduate anthropology student at the University of Yaound in Cameroon. Akem, who grew up in a village in a region south of Okoroba, is here to record how and what Sampson hunts. Every now and then, he fishes a notebook out of a ratty backpack hanging across his chest. A mile into the trek, Sampson turns off the main path and plunges into the underbrush. Soon the three of us are picking our way through termite mounds the size of fire hydrants and slogging across muddy, waist-high streams. Although the canopy shields us from direct sunlight, the forest air is hot and thick with humidity. The murmur of insects is broken by the sound of stork-sized birds flying above the trees, like the beat of distant helicopter blades. As Sampson hurries along, pausing to check buried snares or to examine low- hanging leaves for the recent brush of an animal, he breaks off tiny stems and branches, creating a trail he can use to trace his way home. "It's like his own GPS," Akem says. Most villagers in Okoroba, which lies at the end of a dirt road near the Nigerian border, subsist either by selling cacao or, like Sampson, hunting bushmeat. Lately, logging has thinned the forest, and the locals have had to settle for lean fare: wild birds and rodents. But every hunt brings new possibility, and other villagers' recent monkey kills have made Sampson optimistic. He seems further buoyed by the fresh rut of a bush pig, and as we splash through a creek, he catches the ooh-ooh sound of a monkey. The ensuing chase is unsuccessful, and Akem records what Sampson points out as the missed prey—a red-capped monkey—on a collection of photocopied pictures the researcher keeps stuffed in his backpack. A half hour later, Sampson stops short again, this time at the sound of a squirrel's warning. "Sometimes a squirrel call means there's a viper nearby," Sampson says, warily scanning the brush for the deadly but prized snake. "If you shoot one, you share it with the whole village—after you remove the poison." We press on, dripping sweat and nursing bites from the ant swarms we periodically wade into, which send us into mad sprints through the forest. Then Sampson spots movement through a gap in the trees, motions us to stop, and shoulders his shotgun. He squints for a moment and fires, the kick of the gun shoving him backward. Catching his balance, he plunges into the jungle after his wounded prey.

Sometime around the 1930s, epidemiologists theorize, a hunter much like Sampson walked into a forest a few hundred miles southeast of Okoroba, killed a chimpanzee carrying a then-unknown virus, and became an unwitting driver of human fate. Perhaps blood—infected with simian immuno deficiency virus—dripped down his back into an open wound as he hauled the catch home. Or perhaps he cut his hand while butchering the chimp. But somehow, his own blood came into contact with another primate's blood, and the pathogen changed into a form well built to spread from one human to the next. The hunter then passed the virus, now known as human immuno deficiency virus-1 group M, or HIV, to a fellow villager, and it began its slow leach into the surrounding human population. Today it may seem like the only opportunity to contain HIV came after its discovery in the 1980s. But what if the disease, which has infected or killed an estimated 63 million people, could have been stopped decades earlier? What if that hunter had carried the chimpanzee more carefully that day? For Nathan Wolfe, a biologist at UCLA and head of the project sponsoring Akem's data-gathering, those are the kinds of questions to build a career upon. "Very few people ask whether we could have prevented HIV," Wolfe told me over beers one night last fall in Yaound , the capital of Cameroon. "That's what I encourage people in my lab to think about." Nathan Wolfe Photograph: Joe Toreno Launched in 1999, Wolfe's Cameroon project aims to discover viruses that, like HIV, originate in wild animals and then cross over to infect humans. Known as zoonoses, such pathogens constitute an estimated three- quarters of all emerging human diseases. The list of animal-to-human invaders includes malaria, smallpox, West Nile, Ebola, SARS, and—the threat of the moment—avian influenza. Despite these killers and the near- certainty that new devastating zoonoses will emerge, little is understood about either the range of potential pathogens in the animal kingdom or the way they enter and spread among humans. "We are at the absolute infancy" of understanding the origins of viruses like HIV, says Beatrice Hahn, a professor of medicine at the University of Alabama at Birmingham who last year led the team that traced the origin of HIV to Cameroon. We do know that it takes three steps for a zoonotic agent to become an HIV or a smallpox. First, a human must be exposed to the virus. Then, the virus must either be virulent or become so through mutation. Finally the virus must be able to move from human to human and not kill its host so quickly that it doesn't have time to spread. Each of these steps is a complex biological process, and each presents opportunities to ward off a pandemic. Traditionally, however, the study of infectious disease has focused on containing and tracing outbreaks—say, Ebola in Africa, or HIV around the globe—after a zoonosis has started spreading. (Occasionally, as with avian flu, scientists have identified a potentially dangerous virus one stage before human-to-human transmission.) When it comes to searching for new or unknown viruses among wild animals—and discovering the process through which they cross to humans—few scientists have ventured into the forest. That's what Wolfe hopes to change. His group is organizing a vast range of field research in Cameroon: collecting blood from hunters and their kills, testing wild and domestic birds for avian flu, conducting anthropological surveys of hunters' habits, and investigating sudden die-offs of primates in the jungle. The combined effort is a year-round operation, employing more than 30 full-time scientists, technicians, veterinarians, and IT specialists. Wolfe's group collaborates with dozens more worldwide, from the US Centers for Disease Control and Prevention to the virology lab at France's University of Montpellier. The early results have been promising. The Cameroon project recently discovered at least three unexpected or unknown viruses—all in the same family of RNA retroviruses as HIV—by collecting and analyzing the blood of bushmeat hunters like Sampson. The findings cemented Wolfe's reputation in the world of viral discovery and were dramatic in their own right. But to him, what they really represent is a proof of concept. Now, using $2.5 million he received in 2004 from a National Institutes of Health Pioneer Award as seed money, he's building a network of virus-discovery projects, using Cameroon as the prototype. By monitoring hunters and wild-game markets in a dozen hard-to-reach potential sites in places like the Democratic Republic of Congo, Malaysia, Laos, Madagascar, Paraguay, and China, he plans to build a taxonomy of what's called "viral chatter": the regular transmission of viruses from wild animals to humans, often without any further spread among humans or consequences for the infected. It's the epidemiological equivalent of information blips on a CIA analyst's screen. "In the intelligence community, you have people monitoring intelligence and looking for keywords," Wolfe says. "Every time a keyword comes up, it's not going to signal a terrorist threat. But by studying the patterns, you can begin to understand what you might be looking for. I study some agents that are very unlikely to be pandemic. But we are asking, where did they die out? What are their features?" The answers—assuming Wolfe can find them hidden in the world's tropical forests—will do more than give us a better basic understanding of how viruses work. They will help fine-tune disease models that forecast where the next zoonoses will emerge and potentially allow us to contain a disease through targeted education, economic development, and blood-supply testing. This type of analysis could transform the public health model—from reactive to predictive—giving us a chance we didn't have with HIV.

Wolfe, 36, lived full-time in Cameroon for six years before returning to the US last October. He has a bearded, cherubic face and dark curls that cascade to his shoulders. Around the project's headquarters in Yaound, he is simply referred to as The Doctor, and he projects an easygoing demeanor—favoring flip-flops and T-shirts in the field and the office. When he arrived in Cameroon in 1999, Wolfe had a single contact and spoke no French, the country's principal language. Raised in Detroit, he had studied human biology at Stanford and Oxford before starting a doctoral degree in immunology and infectious diseases at Harvard. For his dissertation, he researched orangutans in a remote part of Borneo, only to venture into town one day and find a scolding email from his mother. "I'm not sure what kind of trouble you are in," she wrote, "but there's a general trying to reach you from the US military." The general turned out to be a colonel named Donald Burke, then head of the Army's AIDS research program at Walter Reed Army Institute of Research. Burke had met Wolfe at a conference and was calling to see whether he would take a post-doc fellowship in Cameroon. Burke had been researching the evolution of HIV and had discovered several new variants of the virus in different parts of the globe. In 1996, he traveled to Cameroon on the invitation of Mpoudi Ngole Eitel, the imposing, mustachioed colonel who headed the country's national AIDS control program. At the time, bushmeat wasn't considered the source of HIV, Burke says. But "just in traveling around the country with Mpoudi, it jumped out at me as a possible route of infection." Together they came up with the idea of screening hunters in remote villages to investigate the diversity of HIV strains. Bushmeat hunters are the perfect "viral interface" because of their close contact with wildlife—particularly primates, whose genetic similarity to humans makes them especially dangerous. Burke asked Wolfe to run that project. It was, at first, a lean operation: In 2001, Wolfe's group relied on a single vehicle—a dilapidated red Toyota Prado—to visit 17 villages and collect blood samples from 4,000 hunters. Mat LeBreton, head of Wolfe's ecology team, recalls using a backpack strap to refasten the car's fuel tank after it fell off. Samples occasionally had to be transported miles by foot or public bus over Cameroon's notoriously impassable roads in a race to process the blood in the 48 hours before it spoiled. From bribe- seeking highway patrols to intransigent tribal chiefs, Wolfe was unfazed by the obstacles. "Nathan seemed to thrive on working in that very difficult, complicated environment," Burke says. "He was an absolute genius." Wolfe would ship the blood samples to the CDC in Atlanta and then fly there himself, spending months at a time examining the viruses in the lab alongside his associates at the center. They decided to look first for simian foamy virus, a primate retrovirus. Foamy virus, so named because of how infected cells look under the microscope, had been found in a handful of laboratory and zoo workers but had never been traced to contact with wild animals. The results of Wolfe's research, published in The Lancet in 2004, showed that 1 percent of hunters were infected with SFV. Whether SFV actually causes symptoms in humans remains unknown, but fears over the disease prompted the Canadian government to begin screening out blood donors who'd had close contact with primates. Wolfe and his colleagues, meanwhile, were also busy screening the same batch of samples for variants of a virus called HTLV. More than 20 million people globally are infected with HTLV-1, a virus that sometimes leads to adult T-cell leukemia, or HTLV-2, a potential source of neurological disease. These are among the six viruses that US blood banks screen every blood donation for. Analy sis of the hunters' blood samples, however, uncovered not only the known HTLV variants but also two entirely new viruses, which the researchers named HTLV-3 and HTLV-4 and whose dangers remain unknown. The implications of those results, published in the Proceedings of the National Academy of Science in 2005, were astounding: Retroviruses similar to HIV were crossing from primates to hunters far more frequently than anyone had expected. The long-ago Cameroonian hunter who acquired SIV was no freak occurrence. Viruses, it turns out, are constantly spilling over from animals to humans. The only reason we don't have frequent pandemics is that most of those viruses have a hard time establishing themselves and then spreading. "There were already some hints of viruses emerging this way," says Burke, who coined the term viral chatter. "What I wasn't ready for was finding them on the order of 1 in 100 people. That means there are literally tens of thousands of people walking around in equatorial Africa harboring viruses in this state."

When Sampson tromps back through the undergrowth, he's gripping a large, bony bird with indigo-lidded eyes. "Harnbeel," he says—the local pronunciation. He drops it to the ground and finishes it off with his machete, then pulls out a piece of plastic and carefully folds the bird into it, placing the bundle in his backpack. "See how he wraps it?" Akem says. "That's to avoid getting the blood on him. They used to just carry them, but this is after our education program." Explaining to the hunters how to avoid blood contact is a major line of defense against animal viruses. For his early research, Wolfe and his team traveled to remote towns and collected from locals not only blood samples but also questionnaires about the villagers' contact with bush animals. Gradually, he expanded his scope. The program now uses hunter volunteers like Sampson to collect blood samples from the animals they kill onto small filter papers that can preserve dried blood spots unrefrigerated for months. A researcher returns periodically to each village and collects the papers, which are cataloged at Wolfe's lab in Yaound and shipped to other labs in the US, Europe, and Africa. Then one of Wolfe's graduate students screens them for known viruses, particularly primate-related pathogens. To expand his network, Wolfe has sought out collaborators working in similar environments. Ann Rimoin, for example, runs a parallel project designed to detect the emergence of monkeypox, a relative of smallpox, in the Democratic Republic of Congo. Wolfe's team is developing universal protocols for gathering blood and anthropological information. The samples will be held in a central repository at UCLA and then sent to experts around the globe. "I think of it almost like being a curator," Wolfe says. Being a curator, though, involves politics as well as science, which for Wolfe means everything from filing the proper inter national blood-shipping permits to convincing the hunters that he and his crew mean well. In the past decade, bushmeat has become a controversial environmental issue across central Africa, as the growing commercial hunting trade supplies more and more food for the continent's swelling cities, threatening the survival of species like chimpanzees and gorillas. Such markets have been found in Europe and the US, too, where several thousand tons of bushmeat are illegally imported each year. Because of the crisis, villagers who subsist on bushmeat are often suspicious of outsiders who come to talk about the practice. For Wolfe and his field teams—relying on unpaid volunteers for their samples—that means a great deal of time spent consulting with village elders, making donations to local schools, and developing the stomach for palm wine. The night after Sampson's hunt, a Cameroonian project leader named Joseph Le Doux Diffo convenes a village-wide meeting in Okoroba to explain the goals of Wolfe's research and provide lessons on how to avoid blood contact during hunting and butchering. "Even a small child in your house can accidentally catch a disease if you have bushmeat there," he tells the assembled villagers. "We are not telling you not to eat meat, but bad diseases are out there now." That evening I sit down outside Sampson's house to watch him butcher the hornbill. He cleans it deftly with his machete, preserving every part of the bird for the evening's meal except the beak, which he sets aside to sell to local Nigerian healers. He explains why he volunteers for the research program: "I am a hunter, and this is my own way of assisting. If it happens that we kill an animal and they discover some drug from this, that would be a good thing." As he finishes carving up the last parts of the bird, I ask him whether he considers that afternoon's hunt successful. "Not a good day, no," he says. "But if I hadn't gone out today, my family would not have eaten."

In a lab at the Blood Systems Research Institute, perched on a hilltop in a San Francisco residential neighborhood, some of the blood samples taken from hunters like Sampson are stashed in Eric Delwart's freezer. Delwart is a professor at UC San Francisco and direc tor of molecular virology at the institute—the disease-research arm of the nation's second-largest blood bank. A few years ago, he stumbled across a paper by a National Institutes of Health researcher describing a new method of identifying unknown viruses. Delwart was so intrigued that he began cold-calling labs in places as far away as Egypt in search of blood samples to scan for undiscovered pathogens. "My hunch," he says, "was that there were a lot of viruses yet to be found." When Delwart heard about Wolfe's sample collection in the forests of Africa, he knew he wanted to get his hands on that blood. And Wolfe was only too happy to send some. One of the potential breakthroughs of Wolfe's work, after all, is the discovery of previously unknown viruses. But doing that requires over coming the same dilemma faced by intelligence analysts: How do you find something you don't know you're looking for? Delwart's method does just that, scanning the blood for any virus, known or unknown. "The key," he says, "is what we call a random PCR." Short for polymerase chain reaction, PCR is a standard lab technique used in everything from paternity tests to criminal DNA analysis. It allows you to amplify a sequence of DNA, creating enough copies to analyze the strand. Typical PCR, however, requires that you know the nucleic acid sequence that makes up the DNA you're looking for. But we obviously don't know that for an undiscovered virus. So, after removing the large human cells and bacteria from a sample, Delwart chops all the remaining genetic material into little pieces and looks at every possible sequence. Then he uses specially designed bioinformatics software to check them against Blast, an NIH database of all known viruses, and identify any that match even remotely. Sequences that repeatedly turn up in the blood but show no similarity to anything in the database could represent new discoveries. Delwart's work is at the forefront of the new science of viral metagenomics, and scientists employ the same technique to look for unknown microbes in everything from seawater and mud to lung fluid. "There could be a new golden age of virology based on this brute-force genomic approach," he says. "The next human epidemic may come from a sick person; it may not. We may find somebody in whom the virus is in the process of adapting. It may never adapt enough to cause an epidemic. But the earlier the warning, the better. That's why the wildlife and the bush hunters are so essential."