• Citizenship :   United States

• Alma mater :   Stanford, Harvard

• Scientific career :

  • Fields :   Virology

  • Institutions   :   Stanford, UCLA

Nathan Daniel Wolfe, Ph.D. (born 24 August 1970) is an American virologist. He was the founder (in 2007) and director of Global Viral[1] and the Lorry I. Lokey Visiting Professor in Human Biology at Stanford University.

Career

Dr. Wolfe spent over eight years conducting biomedical research in both sub-Saharan Africa and Southeast Asia. He is also the founder of [Metabiota, Inc.], which offers both governmental and corporate services for biological threat evaluation and management. He serves on the editorial board of EcoHealth and Scientific American and is a member of DARPA's Defense Science Research Council. His laboratory was among the first to discover and describe the Simian foamy virus.[2]

In 2008, he warned that the world was not ready for a pandemic, such as COVID-19.[3]

In 2012, his book The Viral Storm: The Dawn of a New Pandemic Age[4] was short-listed for the Winton Prize.[5]

As reported in a Wired feature in 2020, Wolfe worked with the German insurance firm Munich Re to offer major corporate leaders pandemic policies, which were not purchased; a stark reality during the ensuing COVID-19 pandemic.[6]

Awards

Wolfe has been awarded more than $40 million in funding from a diverse array of sources including the U.S. Department of Defense, Google.org, the National Institutes of Health, the Skoll Foundation, the Bill & Melinda Gates Foundation and the National Geographic Society.[7]

• Fulbright fellowship recipient (1997)

• National Geographic Emerging Explorer (2004)[2]

• NIH Director's Pioneer Award (2005)

• Popular Science: "Brilliant 10" (2006)

• Rolling Stone: "Top 100 Agents of Change" (2009)

• World Economic Forum's Young Global Leaders (2010)

Press

Wolfe's work has been published in and covered by the popular media including The New York Times, The Economist, Discover and Scientific American. He has appeared on CNN and is a regular TED presenter. He has also appeared as one of Time magazine's "Time 100" for 2011.

Personal life

Wolfe is married to the playwright Lauren Gunderson and has 2 sons. As part of his work, he has lived in Cameroon, Malaysia and Uganda.[5]

References

• ^ Langreth, Robert. Finding the Next Epidemic Before It Kills. Forbes. 2 November 2009.
• a b Geographic, National (June 2020). "Grantee 2004-2005: Nathan D. Wolfe". National Geographic Emerging Explorers. Retrieved 9 July2020.
• ^ Dwyer, Paul (December 24, 2020). "World-renowned virologist warned in 2008 about future epidemics". CNN. Retrieved January 3, 2021.
• ^ Nathan Wolfe (2011), The Viral Storm: The Dawn of a New Pandemic Age, Henry Holt & Co.
• a b "Nathan Wolfe". DCP3. Archived from the original on 29 June 2020. Retrieved 29 June 2020.
• ^ Ratliff, Evan (July–August 2020). "We Can Protect the Economy From Pandemics. Why Didn't We?". Wired. Retrieved 9 July 2020.
• ^ "Nathan Daniel Wolfe". Stanford University. Retrieved 29 June 2020.

Intro 

Human hunter/gatherer populations currently suffer, and presumably have suffered for millions of years, from infectious diseases similar or identical to diseases of other wild primate populations. However, the most important infectious diseases of modern food-producing human populations also include diseases that could have emerged only within the past 11,000 years, following the rise of agriculture1,2. We infer this because, as discussed below, these diseases can only be sustained in large dense human populations that did not exist anywhere in the world before agriculture. What were the sources of our major infectious diseases, including these ‘new’ ones? Why do so many animal pathogens, including virulent viruses like Ebola and Marburg, periodically infect human hosts but then fail to establish themselves in human populations?

A tentative earlier formulation1 noted that major infectious diseases of temperate zones seem to have arisen overwhelmingly in the Old World (Africa, Asia and Europe), often from diseases of Old World domestic animals. Hence one goal of this article is to reappraise that conclusion in the light of studies of the past decade. Another goal is to extend the analysis to origins of tropical diseases3. We shall show that they also arose mainly in the Old World, but for different reasons, and mostly not from diseases of domestic animals.

These results provide a framework for addressing unanswered questions about the evolution of human infectious diseases—questions not only of practical importance to physicians, and to all the rest of us as potential victims, but also of intellectual interest to historians and evolutionary biologists. Historians increasingly recognize that infectious diseases have had major effects on the course of history; for example, on the European conquest of Native Americans and Pacific Islanders, the inability of Europeans to conquer the Old World tropics for many centuries, the failure of Napoleon’s invasion of Russia, and the failure of the French attempt to complete construction of a Panama Canal4–6. Evolutionary biologists realize that infectious diseases, as a leading cause of human morbidity and mortality, have exerted important selective forces on our genomes2,7.

We begin by defining five stages in the evolutionary transformation of an animal pathogen into a specialized pathogen of humans, and by considering why so many pathogens fail to make the transition from one stage to the next. We then assemble a database of 15 temperate and 10 tropical diseases of high evolutionary and/or historical impact, and we compare their characteristics and origins. Our concluding section lays out some unresolved questions and suggests two expanded research priorities. We restrict our discussion to unicellular microbial pathogens. We exclude macroparasites (in the sense of ref. 7), as well as normally benign commensals that cause serious illness only in weakened hosts. The extensive Supplementary Information provides details and references on our 25 diseases, robustness tests of our conclusions, factors affecting transitions between disease stages, and modern practices altering the risk of emergence of new diseases.

ON FEBRUARY 18th a glimmer of hope died. The Population Council, a big international charity, announced the results of one of the largest trials yet undertaken of a vaginal microbicide intended to protect the user from infection with HIV, the virus that causes AIDS. It failed. Carraguard, whose principal ingredient is a gel derived from seaweed, proved no more effective than a placebo in an experiment involving 6,000 South African women.

AIDS kills over 2m people a year. A way of stopping it spreading is urgently required. Yet according to Nathan Wolfe, a virologist at the University of California, Los Angeles, things need never have got this bad. If there had been, in the 1970s, a programme searching for unrecognised diseases in Africa then AIDS would have been noticed long before so many people had started dying from it. Microbicides and other interventions could have been tested when only hundreds of thousands were infected, rather than tens of millions. AIDS would still have been horrible, but not nearly as horrible as it has become.

To try to stop this happening again, Dr Wolfe is attempting to create what he calls the Global Viral Forecasting Initiative (GVFI). This is still a pilot project, with only half a dozen sites in Africa and Asia. But he hopes, if he can raise the $50m he needs, to build it into a planet-wide network that can forecast epidemics before they happen, and thus let people prepare their defences well in advance.

Dr Wolfe outlined his ideas, and the research that has led him to believe they are feasible, to this year's meeting of the American Association for the Advancement of Science (AAAS) in Boston. He began his work nearly a decade ago in Cameroon, in a project reminiscent of the 19th-century animal-collecting expeditions that pushed into the forest to look for new species. Except that his quarry is viruses, not butterflies and birds.

Small-game hunter

Almost all human viruses whose origins are known have come from animals. But it is not simply a matter of an animal virus suddenly finding humans to be a congenial host, and flourishing as a result. With AIDS, for example, the global epidemic is caused by what was originally a chimpanzee virus. There is, however, a second form of AIDS, caused by a monkey virus. This has not become global. It is pretty much restricted to West Africa. Moreover, there are a further two very rare forms caused by different versions of the chimpanzee virus. These rare forms are examples of what Dr Wolfe calls viral chatter, a term borrowed from intelligence agencies which monitor telephones for the use of certain words or unusual patterns of communication.

His thesis is that there is continual low-level interchange of viruses between species. That is particularly so for people, such as hunters and farmers, who are in constant and often bloody proximity to animals. His hope is that by monitoring this viral chatter he will be able to spot pathogens before they take the second, crucial evolutionary step of being able to transmit themselves from one human to another.

So far, he has concentrated his efforts on a group known as retroviruses, of which HIV is one. He has already found three examples of “foamy viruses” jumping from wild apes and monkeys to Cameroonian hunters. At the moment, no known foamy virus can spread between people. But until the 20th century that was true of the simian equivalents of HIV.

He has also found two new members of a group called HTLV that have moved from monkeys to men. Since HTLV-1, an example of the group discovered several decades ago, has already spread around the world, these cases are particularly noteworthy. HTLV-1 is not as common as HIV, and causes symptoms in only 5-10% of those it infects. But those symptoms can include a fatal leukaemia. And a different type of HTLV might not be so choosy about whom it kills

Even more worryingly, Dr Wolfe has found many examples of viruses recombining in his Cameroonian hunters. Recombined viruses often have properties present in neither parent. Sometimes these include the ability to jump from human to human. The pandemic version of HIV is the result of such a recombination.

The next stage of the project is to try to gather as complete an inventory as possible of animal viruses, and Dr Wolfe has enlisted his hunters to take blood samples from whatever they catch. He is collaborating with Eric Delwart and Joe DeRisi of the University of California, San Francisco, to screen this blood for unknown viral genes that indicate new species. The GVFI will also look at people, monitoring symptoms of ill health of unknown cause and trying to match these with unusual viruses.

Nor, if Dr Wolfe can raise the money, will the project be confined to tropical forests. Animal markets are next in line. Dr Wolfe is working with [Dr. Peter Daszak (born 1965)],  of the Consortium for Conservation Medicine, to study the so-called wet markets of China where SARS began in 2002. They will inspect the animals sold in them, and test the stallholders and customers for signs of dodgy viruses. Dr Daszak is a co-author of a study published in this week's Nature that maps the global “hot spots” of emerging diseases and concludes, as Dr Wolfe has, that the real threat lies in the tropics. That is despite the fact that most new diseases are (as with AIDS) first noticed in rich countries.

If and when the GVFI is running smoothly, Dr Wolfe hopes to see not only what is threatening, but also to identify the general characteristics (if any) that threatening viruses share. If some features are regularly associated with a propensity to become pandemic, then forecasting outbreaks of new viral diseases will become easier and more scientific. At that point, this branch of medicine will be able to make the most important leap of all—from cure to prevention. And then a catastrophe like AIDS will need never happen again.

Newswise — The Global Viral Forecasting Initiative (GVFI), a nonprofit research initiative dedicated to preventing pandemics, has received $11 million dollars from Google.org and The Skoll Foundation. The support, which includes $5.5 million dollars from each organization, represents the largest grant to date from Google.org.

GVFI, an organization whose mission it is to prevent future pandemics before they become fully established, brings together fieldwork in disease hotspots throughout the world with cutting edge laboratory science aimed at the discovery of new pathogens.

"Pandemics pose an enormous threat to us all," said Sally Osberg, President and CEO of the Skoll Foundation. " Often, by the time a new virus is discovered, it's too late to contain it. The innovative Global Viral Forecasting Initiative is aimed at finding dangerous viruses when it is still possible to limit their spread. The Skoll Foundation is proud to support this pioneering and important work."

Through collaborative studies in Cameroon, China, Democratic Republic of Congo, Lao PDR, Madagascar, and Malaysia, GVFI tracks emergent pandemics to their source, working to provide potentially vital months or years of advanced warning before the next HIV or SARS emerges on the global stage.

"The 1918 flu outbreak cost more lives than World War I. Most epidemiologists agree - and worry - that the world is overdue for another dangerous flu pandemic," says Dr. Larry Brilliant, Executive Director of Google.org. "The cutting-edge work of Nathan Wolfe and his network of public health stars may be one of the world's best bets to prevent the next pandemic." GVFI's strategy for preventing pandemics comes out of more than a decade of research by its founder and director, Dr. Nathan Wolfe, who holds the Lorry I. Lokey Visiting Professorship in Human Biology at Stanford University. Utilizing $2.5m in seed funding from the prestigious NIH Director's Pioneer Award Dr. Wolfe and his team developed the global early warning system that will now be expanded with the Google.org and Skoll funding. The early warning system has already allowed the GVFI team and their collaborators to discover a range of novel viruses and has provided the first evidence that retroviruses continue to cross from animals to humans.

"Nothing is more important to me than stimulating and sustaining deep innovation, especially for early career investigators like Dr. Nathan Wolfe," said NIH Director Elias A. Zerhouni, M.D. "He is a highly creative researcher who is tackling important scientific challenges with inventive ideas, ideas that are now garnering support from other sectors."

"The partnership between GVFI, Google.org, and the Skoll Foundation gives us the opportunity to take techniques we've developed over the last ten years and implement them globally" says Dr. Nathan Wolfe, Director of GVFI. "With this support, GVFI along with our collaborators will work to change the way the world prepares for the next pandemic."

http://www.gvfi.org

• Bio of GVFI Founder and Director, Dr. Nathan Wolfe  :  Dr. Nathan Wolfe is the founder and director of the Global Viral Forecasting Initiative (GVFI), and holds the Lorry I. Lokey Visiting Professorship in Human Biology at Stanford University. He received his bachelor's degree from Stanford in 1993 and his doctorate in Immunology & Infectious Diseases from Harvard in 1998. The recipient of a Fulbright fellowship in 1997, Dr. Wolfe was awarded the National Institutes of Health (NIH) International Research Scientist Development Award in 1999 and the prestigious NIH Director's Pioneer Award in 2005. Dr. Wolfe has published over 50 articles and chapters. Among his major findings include the discovery of the first evidence of natural transmission of retroviruses from nonhuman primates to humans. His work has been published in or covered by Nature, Science, The Lancet, PNAS, JAMA, The New York Times, The Economist, Wired, Discover, Scientific American, NPR, Popular Science, Seed, and Forbes. Dr. Wolfe's research has generated support of over $20m in grants and contracts from Google.org, The Skoll Foundation, NIH, the National Science Foundation, the Bill & Melinda Gates Foundation, the National Geographic Society, Merck Research Laboratories and various branches of the US Department of Defense. He has extensive consulting experience and has served on a number of advisory and editorial boards, including, since 2004, the editorial board of EcoHealth. Dr. Wolfe has over eight years of full-time experience living and conducting biomedical research in Southeast Asia (Malaysia) and sub-Saharan Africa (Cameroon, Uganda). He currently has active research and public health projects in eleven countries throughout the world.

Shortly after one of us ( [Dr. Jared Mason Diamond (born 1937)]) boarded a flight from Hong Kong back to Los Angeles, the passenger in the next seat sneezed. She sneezed again—and again—and then she began coughing. Finally she gagged, pulled out the vomit bag from the seat back in front of her, threw up into the bag, stood up, squeezed past, and lurched to the toilet at the front of the plane. The woman was obviously miserable, but sympathy for her pain was not what I felt. Instead I was frightened and asked the flight attendant to move me to a seat as far from her as possible.

All I could think of was another sick person, a man from Guangdong province in southern China, who spent the night of February 21, 2003, at the Metropole Hotel in Hong Kong, an upscale establishment with a swimming pool, fitness center, restaurants, a bar, and all kinds of areas where visitors could socialize and connect. The man stayed a single night in room 911. Unfortunately for him and for many other people, he had picked up severe acute respiratory syndrome, or SARS—perhaps directly from an infected bat or from a small, arboreal mammal called a civet, common in one of Guangdong’s famous “wet markets” that sell wild animals for food, or else from a person or chain of people ultimately infected from one of those animal sources.

In the course of his brief stay, the man initiated a SARS “super spreader” event that led to at least 16 more SARS cases among the hotel’s guests and visitors and then to hundreds of other cases throughout Asia, Europe, and North America as those guests and visitors continued on their travels—just as my neighbor was now traveling to L.A. The infectiousness of room 911’s guest can be gauged from the fact that three months later, the carpet right outside the door and near the hotel elevator yielded genetic evidence of the SARS virus, presumably spewed out in his own sneezing, coughing, or vomiting.

I didn’t end up with SARS, but my experience drives home the terrifying prospect of a novel, unstoppable infectious disease. Globalization, changing climate, and the threat of drug resistance have conspired to set the stage for that perfect microbial storm: a situation in which an emerging pathogen—another HIV or smallpox, perhaps—might burst on the scene and kill millions before we can respond.

Pathogen ParadoxTo grasp the risk, we first must understand why any microbe would evolve to sicken or kill us. In evolutionary terms, how does destroying its host help a microbe to survive?

Think of your body as a potential “habitat” for tiny microbes, just as a forest provides a habitat for bigger creatures like birds and squirrels. The species living in the forests of our bodies include lice, worms, bacteria, viruses, and amoebas. Many of those denizens are benign and cause us no harm. But some microbes seem to go out of their way to make us sick—either mildly sick, as in the case of the common cold, or else sick to the point of killing us, as in the case of smallpox.

Killer microbes have long posed a paradox for evolutionary biologists. Why would a microbe evolve to devastate the very habitat on which it depends? By analogy, you might reason that there should be no squirrels that destroy the forest they live in, because such a species would quickly go extinct.

The answer stems from the fact that in order to survive over the long haul, any microbe restricted to humans must be able to spread from one victim to the next. There is a simple mathematical requirement here: On average, the germ must infect at least one new victim for every old one who either dies or recovers and purges himself of the microbe. If the average number of new victims per old drops to fewer than one, then the spread of the microbe is doomed.

A microbe can’t walk or fly from one host to the next. Instead it must resort to a range of nefarious tricks. What from our point of view is simply a disease symptom can, from the bug’s perspective, be an all-important means of enlisting our help to move around. Common microbe tricks are to make us cough or sneeze, suffer from diarrhea, or develop open sores on our skin. Respectively, these symptoms spread the microbe into our exhaled breath, into the local water supply via our feces, and onto the skin of those who touch us, explaining why a microbe might want to induce unpleasant symptoms in its victims.

Evolutionary biologists reason that keeping us alive and pumping out new microbes would be an excellent strategy for such a bug, which might therefore evolve to be less, not more, virulent over time. An example comes from the history of syphilis. When it first appeared in Europe in 1495, it caused severe and painful symptoms within a few months, but by 1546 it had begun evolving into the slowly progressing disease that we know today.

Yet if keeping us alive is strategically sound, why do some pathogens go so far as to actually kill us?

Sometimes a microbe’s deadly rampage through a human population stems from an accident of nature. For instance, the microbe could be comfortably adapted to some animal host that it routinely inhabits without deadly consequences, but it could be maladapted to the human environment. The microbe may rarely infect people, but when it does, it may kill the human host, who becomes a literal dead end for the virus as well.

But what of those killer microbes that target humans, making us their primary host? Their survival strategy, evolutionary biologists now realize, differs from that of a disease like syphilis but works just as well. Take the cholera bacterium that gives us diarrhea or the smallpox virus that makes us develop skin sores; both of these can kill us in days to weeks. Such virulence may be evolutionarily favored if, in the brief time between our becoming infected and dying, the fatal symptoms spread trillions of microbes to potential new victims. The fact that we may die is unfortunate for us but an acceptable cost for the microbe. In the world of evolution and natural selection, anything that the microbe does to us is fair—just as long as at least one new victim gets infected for each old one.

Hence the recipe for a killer disease is for the microbe to achieve a balance between two things: the probability of its killing us quickly once we become infected and its efficiency in leading our bodies to transmit the microbe to new victims.

From left: influenza, SARS, Ebola virus, Tuberculosis in sputum | All images: creative commons

Those two things are connected. The greater its efficiency in inducing lethal, bug-spreading syndromes (good for the microbe), the faster the microbe kills us (bad for the microbe). Following this logic, a pathogen may end up killing lots of people by one of two routes. In the style of HIV, it can keep the disease carrier alive for a long time, infecting new victims over the course of months or years. Or in the style of smallpox and cholera, it might kill quickly with explosive symptoms that can spread an infection to dozens of new victims within a day.

Searching for the Source For epidemiologists hoping to stanch such outbreaks, tracking killer germs to the source is key. Do deadly pandemics arise spontaneously in human populations? Or are they “gifts” from other species, mutating and then crossing over to make us ill? Which ecosystems are spawning them, and can we catch them at the start, before they cause too much damage?

Some answers can be found in the history of yellow fever, a virus spread by mosquitoes. The cause of devastating human epidemics throughout history, yellow fever is still rife in tropical South America and Africa. Biologists now understand that yellow fever arose in tropical African monkeys, which, through the mosquito vector, infected (and continue to infect) tropical African people, some of whom unintentionally carried yellow fever with them on slave ships several hundred years ago to South America.

Mosquitoes bit the infected slaves and in turn carried the virus to South American monkeys. In due course, mosquitoes bit infected monkeys and transmitted yellow fever right back to the human population there.

In Venezuela today, the Ministry of Health keeps a lookout for the appearance of unusual numbers of dead wild monkeys, such as howler monkeys. Because the monkeys are so susceptible to yellow fever and can act as a reservoir from which the virus leaps to the human population, an explosion of monkey deaths serves as an advance warning system, signaling the need to vaccinate humans in the vicinity.

This pattern of cross-infection from animals to humans is par for the course in emerging infectious disease. In fact, the big killer diseases of history all came to us from microbes living in other species, overwhelmingly from other warm-blooded mammals and, to a lesser extent, from birds.

On reflection, this all makes sense. Each new animal host to which a microbe adapts represents a new habitat. It is easiest for a microbe to jump between closely related habitats, from an animal species with one sort of body chemistry to a closely related animal species with very similar body chemistry.

In the tropics, disease sources have included a host of wild animals, most notably the nonhuman primates. We can thank our primate cousins not just for yellow fever but also for HIV, dengue fever, hepatitis B, and vivax malaria. Other wild animal disease donors include rats, the source of the plague and typhus.

In temperate regions like the United States, meanwhile, ticks in suburban neighborhoods and domestic livestock living in proximity to humans have posed threats. Mammalian reservoirs like mice and chipmunks carry Lyme disease and tularemia; ticks transmit these diseases to humans. Cattle probably gave rise to the measles and tuberculosis. Smallpox is likely to have come from camels, biologists say, and flu from pigs and ducks.

The Next Wave Today, with fewer people tending farms and more living in the suburbs, things have certainly changed. The principles of infectious disease are the same as they have always been, but modern conditions, including life in proximity to pets and mammal-filled woods, are exposing us to new pathogen reservoirs and new modes of transmitting disease.

One of us ([Dr. Nathan Daniel Wolfe (born 1970)]) has spent much of the last six years in the tropical African country of Cameroon, studying the kinds of interspecies jumps that such conditions might spawn. To examine the mechanisms, I worked with rural hunters who butchered wild animals for food. I collected blood samples from the hunters, from other people in their community, and from their animal prey. By testing all those samples, I identified microbes inhabiting the animal reservoirs and focused on those that showed up in the hunters’ blood, making them candidates for firing up human disease.

One evening I asked a group of hunters if they had ever cut themselves while butchering wild monkeys or apes. The response was incredulous laughter: “You don’t know the answer to that?” Of course, they said. All of them had cut themselves once or more, thereby giving themselves ample opportunity to get infected from animal blood.

On reflection, I shouldn’t have been surprised. I can’t count all the times I have cut myself while chopping onions. The difference is that onions aren’t closely related to us humans, and an onion virus has far less chance of taking hold in us than does a monkey virus.

The statistics are telling. Researchers like Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh in Scotland, have found at least 868 human pathogens that infect both animals and humans, although some are not as fearsome as they seem.

Overhyped microbes include anthrax (famous for the U.S. mail attacks in 2000), the Ebola and Marburg viruses (which can cause dramatic bleeding and high fever in their victims), and the prion agent of mad cow disease (otherwise known as bovine spongiform encephalopathy, or BSE), which kills people by making their nervous systems degenerate. These bugs arouse terror because they kill so many of their victims. For example, in the 2000 Ebola outbreak, which struck the Gulu district of Uganda, 53 percent of the 425 people who contracted the disease died. The case fatality rate for BSE is 100 percent.

Although spectacularly lethal, these pathogens generally kill just a few hundred people at a time and then burn themselves out. They transmit from human to human too inefficiently to spread very widely; 100 percent of a small number of victims is still a small number of fatalities.

There are many reasons why an agent leaping from animals to humans might not affect more individuals. For example, humans do not normally bite, scratch, hunt, or eat each other. This surely contributes to the rarity or nonexistence of human-to-human transmission of rabies (acquired by the bite of an infected dog or bat); cat-scratch disease (which causes skin lesions and swollen lymph nodes); tularemia (a disease, often acquired when hunting and cutting up an infected rabbit, that can cause skin ulcers, swollen lymph nodes, and fever); and BSE (probably acquired by eating the nervous system tissue of infected cows).

Some outbreaks, once recognized, are relatively easy to control. Anthrax is treatable with antibiotics; after an initial malaria-like stage, the rapid onset and severity of Ebola and Marburg symptoms have made identification and containment straightforward.

In fact, within the last 40 years, only HIV (derived from chimpanzees) has taken off to cause a pandemic.

Back to the Future If not anthrax or Ebola, which pathogens might spawn the next deadly pandemic in our midst?

New pandemics are most likely to be triggered by mutant strains of familiar microbe species, especially those that have caused plagues by churning out mutant strains in the past. For example, the highest known epidemic death toll in history was caused by a new strain of influenza virus that killed more than 20 million people in 1918 and 1919. Unfairly named Spanish influenza, it apparently emerged in Kansas during World War I, was carried by American troops to Europe, and then spread around the world in three waves before ebbing in outbreaks of declining virulence in the 1920s. Mutant strains of influenza or cholera remain prime candidates for another deadly outbreak. Both can persist in animal reservoirs or the environment, and both are adept at spawning new strains. Both pathogens also transmit efficiently, and it is possible that these two important diseases of the past could become important diseases of the future.

A future pandemic could also come from tuberculosis. New mutants have already arisen through the mechanism of drug resistance. And the disease lives on in the human population, especially among those with weakened immunity, including patients with HIV.

Also of concern are emerging sexually transmitted diseases, which, once introduced, may be difficult to control because it is hard to persuade humans to change sexual behavior or to abstain from sex. HIV offers a grim warning: Despite its huge global impact, the AIDS epidemic would have been far worse if the sexual transmissibility of HIV (which is actually rather modest) had equaled that of some other sexually transmitted agents, such as human papilloma virus (HPV). While the probability of HIV transmission varies with the stage of the disease and the type of sexual contact, it appears to pass from infected to uninfected individuals in less than 1 percent of acts of unprotected heterosexual intercourse, while the corresponding probability of HPV transmission is thought to be higher than 5 percent—probably much higher.

Similarly, it could be difficult to control emerging pathogens transmitted by pets, which increasingly include exotic species along with traditional domestic animals like dogs and cats. Already we are at risk of catching rabies from our dogs, toxoplasmosis and cat-scratch disease from our cats, and psittacosis from our parrots. Most people now accept the need to cull millions of farmyard animals in the face of epidemics like mad cow disease, but it is hard to imagine killing beloved puppies, bunnies, and kittens, even if those pets do turn out to offer a pathway for a dangerous new disease.

Have Plague, Will Travel Once a killer disease has emerged, modern societies offer new ways for it to flourish and spread. Global travel, the close quarters of the urban environment, climate change, the evolution of drug-resistant microbes, and increasing numbers of the elderly or antibiotic-treated immunosuppressed could all aid the next great plague.

For example, rapid urbanization in Africa could transform yellow fever, chikungunya fever (which causes severe joint pain and fever), and other rural African arboviruses (viruses, including yellow fever, spread by bloodsucking insects) into plagues of African cities, as has already happened with dengue hemorrhagic fever. One of us (Wolfe) theorizes that this might follow increasing demand in those cities for bush meat. Like urban people everywhere, urban Africans love to eat the foods enjoyed by their village-dwelling ancestors, and in tropical Africa this means bush meat. In that respect it’s similar to the smoked fish and bagels that I eat in the United States, which give me some comforting memory of my Eastern European roots. But there’s an important difference: The wild game that I see served in fancy restaurants in the capital of Cameroon is much more likely to transmit a dangerous virus to the person who hunted and butchered it, or to the cook who prepared it, or to the restaurant patron who ate the meat undercooked, than is my brunch of smoked fish and bagels.

By connecting distant places, meanwhile, globalization permits the long-distance transfer of microbes along with their insect vectors and their human victims, as evidenced not only by the spread of HIV around the world, but also by North American cases of cholera and SARS brought by infected passengers on jet flights from South America and Asia, respectively. Indeed, when a flight from Buenos Aires to Los Angeles stopped in Lima in 1992, it picked up some seafood infected with the cholera then making the rounds in Peru. As a result, dozens of passengers who arrived in Los Angeles, some of whom then changed planes and flew on to Nevada and even as far as Japan, found that they had contracted cholera. Within days that single airplane spread cholera 10,000 miles around the whole rim of the Pacific Basin.

Consider as well those diseases thought of as “just” tropical because they are transmitted by tropical vectors: malaria transmitted by mosquitoes, sleeping sickness spread by tsetse flies, and Chagas’ disease (associated with edema, fever, and heart disease) spread by kissing bugs. How will we feel about those tropical diseases if global warming enables their vectors to spread into temperate zones? While microbe and vector movement can be difficult to detect, modeling suggests that global warming will expand the reach of malaria to higher latitudes and into tropical mountain regions.

The transmission of emerging diseases has also been enhanced by a host of modern practices and technologies. The commercial bush meat trade has introduced retroviruses into human populations. Ecotourism has exposed first-world tourists to cutaneous leishmaniasis and other third-world diseases. Underequipped rural hospitals have facilitated Ebola virus outbreaks in Africa. Air conditioners and water circulation systems have spread Legionnaires’ disease. Industrial food production was responsible in Europe for the spread of BSE. And intravenous drug use and blood transfusion have both spread HIV and hepatitis B and C.

All this shows that disease prevention and treatment need to be supplemented by a new effort: disease forecasting. This refers to the early detection of potential pandemics at a stage when we might still be able to localize them, before they have had the opportunity to infect a high percentage of the local population and thereby spread around the world, as happened with HIV. Already one of us (Wolfe) is working through a new initiative, the Global Viral Forecasting Initiative (GVFI), to do just that. GVFI works in countries throughout the world to monitor the entry and movement of new agents before they become pandemics. By studying emerging agents at the interface between humans and animals, GVFI hopes to stop new epidemics before they explode. Monitoring for the emergence of both new sexually transmitted diseases and pet-associated diseases would be good investments.

The predictions here are admittedly educated guesses—but they are educated by some of the best science available. The time to act is now. If we don’t, then we will continue to be like the cardiologists of the 1950s, waiting for their patients’ heart attacks and doing little to prevent them. If we do act, we have the potential to avert the next HIV, saving millions of lives and billions of dollars. The choice seems obvious.

In 1967, the country's surgeon general, William Stewart, famously said, "The time has come to close the book on infectious diseases. We have basically wiped out infection in the United States." This premature victory declaration, perhaps based on early public health victories over 19th-century infectious diseases, has entered the lore of epidemiologists who know that, if anything, the time has come to open the book to a new and dangerous chapter on 21st-century communicable diseases.

Indeed, to the epidemiological community, the Influenza Pandemic of 2009 is one of the most widely anticipated diseases in history. Epidemiologists have been shouting from rooftops that a pandemic (or, a world-wide epidemic) of influenza is overdue, and that it is not a matter of "if" but "when." The current pathogen creating the threat is actually a mixture of viral genetic elements from all over the globe that have sorted, shifted, sorted, shifted, drifted and recombined to form this worrisome virus.

No one knows if the 2009 swine flu will behave like the 1918 Spanish flu that killed 50 million to 100 million world-wide, or like the 1957 Asian flu and 1968 Hong Kong flu that killed far fewer. This 2009 flu may weaken and lose its virulence, or strengthen and gain virulence -- we just do not know.

Here's the good news: Compared with a few years ago, the world is somewhat better prepared to deal with pandemic influenza. There have been training meetings, table-top exercises, dry runs and preparedness drills at virtually every level of government and civil society. World Health Organization member states have agreed on a set of regulations that require all members to report the status of diseases of global significance within their borders. We have two effective antiviral drugs, at least for the time being. There have been some breakthroughs to reduce the time required to get effective vaccines into the field, and there is even a small chance that last year's seasonal vaccine will help protect lives from H1N1. In the U.S. at least, influenza surveillance has improved.

Here's the bad news: Today, we remain underprepared for any pandemic or major outbreak, whether it comes from newly emerging infectious diseases, bioterror attack or laboratory accident. We do not have the best general disease surveillance systems or "surge" capacity in our hospitals and health-care facilities. We do not have enough beds, respirators or seasoned public-health staff (many of whom, because of the financial meltdown, ironically got pink slips from their state and county health departments days or even hours before WHO declared we are at a Phase 5 alert, one step short of its highest global level). We not only need to retain the public-health people we have, we quickly need to train a new generation of 21st-century workers who know both the old diseases and have mastered the computer and other digital technologies and genomic advances to keep them ahead of the newest emerging threats.

And there is worse news: The 2009 swine flu will not be the last and may not be the worst pandemic that we will face in the coming years. Indeed, we might be entering an Age of Pandemics.

In our lifetimes, or our children's lifetimes, we will face a broad array of dangerous emerging 21st-century diseases, man-made or natural, brand-new or old, newly resistant to our current vaccines and antiviral drugs. You can bet on it.

One of the top scientists in the world did bet on it. A few years ago, Lord Martin Rees, who holds three of the most distinguished titles in the scientific world (Astronomer Royal; Master of Trinity College, Cambridge; and head of the 350-year-old Royal Society, London) offered a $1,000 wager that bioterror or bioerror would unleash a catastrophic event claiming one million lives in the next two decades. Lord Rees said: "There's real concern about whether our civilization can be safeguarded without us sacrificing too much in terms of privacy, diversity and individualism."

Risks from bioterror are unpredictable, of course, but I think it's fair to say that world-wide access to infectious agents and basic biological know-how has grown more rapidly than even the exponential growth of computing power. According to Moore's law, the number of transistors on a chip doubles in 18 to 24 months -- or, said another way, the "the bang for the buck" in computers doubles in less than two years.

The technologies supporting bioterror have exploded even faster than computing power. The cost of genomic sequencing, as one example of a supporting technology, has gone down from the nearly $1 billion it cost for the first full human DNA sequences to the low thousands for consumers in the coming years. Genetic engineering of viruses is much less complex and far less expensive than sequencing human DNA. Bioterror weapons are cheap and do not need huge labs or government support. They are the poor man's WMD.

Naturally occurring diseases with pandemic potential are much more ubiquitous and more certain to occur. Over the last decades, we have seen more than three dozen new infectious diseases appear, some of which could kill millions of people with one or two unlucky gene mutations or one or two unfavorable environmental changes. The risks of pandemics only increase as the human population grows, the world loses greenbelts, uninhabited land disappears and more humans hunt and eat wild animals.

• "Look up,’’ Nathan Wolfe barked. I didn’t respond immediately, so the next suggestion came with an elbow to the ribs: “Take your head out of that map.” We were standing on the side of “the road,” a dirt highway that passes through the center of Mindourou, a dusty logging village in southeastern Cameroon. Wolfe, the director of Global Viral Forecasting, and several colleagues were in the midst of a ten-hour drive from the capital, Yaoundé, to a town called Ngoila, one of the many sites that G.V.F. has established in the past decade to monitor the emergence of deadly viruses from the jungles of Central Africa. He nodded toward a couple who had just pulled up beside us on a Chinese motorcycle. The driver wore flip-flops and a red tracksuit. His passenger, dressed in a pale-blue shirt and a matching pillbox hat, looked as if she were on her way to church. But that wasn’t where they were headed. Her right arm was wrapped around the driver’s waist. In her left, she clutched the lengthy tail of a freshly killed agile mangabey, a monkey often found in the lush forests of the region.
• “Those monkeys are viral warehouses,” Wolfe said to me, as the couple drove toward the market, dragging their bloody merchandise behind them. Mangabeys carry many viruses that infect humans, including one that may cause a rare form of T-cell leukemia and another, simian foamy virus, the ultimate impact of which is not yet known. Wolfe is a forty-year-old biologist from Stanford University; a swarthy man with a studiously dishevelled look, he comes off as a cross between a pirate and a graduate student. He is also the world’s most prominent virus hunter, and he spends much of his time sifting through the blood of wild animals. “When I see a monkey like that dragged through the street, bloody, on the way to market, it’s like looking at a loaded weapon,’’ he said. “It scares me.”
• For much of the ride from Yaoundé, Wolfe had been expounding upon the health dangers posed by bushmeat, the common term for tropical wild game, which includes monkeys, gorillas, chimpanzees, porcupines, scaly anteaters, cane rats, and other animals. Humans have subsisted on bushmeat for millennia, and in this part of Africa it remains a principal source of protein—sometimes the only source. Central Africans consume at least two million tons a year. It is not easy to convince somebody whose only alternative is hunger and malnutrition that eating monkeys or apes can be more of a threat to him than it was to his ancestors. Yet the health risks are enormous—not just for the Africans who kill and eat them but for billions of others throughout the world. If not for the consumption of bushmeat, aids, which has so far killed thirty million people and infected more than twice that number, would never have spread so insidiously across the planet. That pandemic, the most lethal of modern times, began nearly a century ago, in Cameroon, when a chimpanzee virus was transmitted to the blood of someone who almost certainly hunted, butchered, or ate it.
• Deadly viruses have always threatened humanity, but a virus can travel only as far as the cells it infects. For most of human history, that wasn’t very far. A few hundred years ago, if H.I.V. had passed from an ape to a hunter, that person would have become sick and died. He might even have infected his entire village, killing everyone around him. But that would have been the end of it. There were no motorcycles to carry the infected carcasses of slaughtered apes to markets in Yaoundé, and, for that matter, no airplanes to ship them to Paris or New York. Forests had been impenetrable for thousands of years. In the past few decades, however, new roads, built largely by logging companies, have brought economic opportunity to millions of Africans, along with better medicine, clean water, and improved access to education. Yet, seen from the perspective of a virus, those roads, combined with air travel, have created another kind of opportunity, transforming humanity into one long chain of easily infected hosts—no less vulnerable in California than in Cameroon.
• Genetically, we are not an especially diverse species; an epidemic that can kill people in one part of the world can kill them in any other. “There is simply no greater threat to humanity than a viral pandemic,” Wolfe told me. “What is more likely to kill millions of people? Nuclear war or a virus that makes the leap from animal to man? If, tomorrow, I had to go to Las Vegas and place a bet on the next great killer, I would put all my money on a virus.” The Nobel Prize-winning molecular biologist Joshua Lederberg once expressed a similar sentiment, writing that viruses were “the single biggest threat to man’s continued dominance on this planet.” For most experts, the question isn’t whether another deadly virus will appear, either naturally or from a lab in the form of a biological weapon, but when. “We cannot afford to let another epidemic like aids get out of control,” Wolfe said. “Why are we sitting around passively waiting until new diseases infect half the globe?”
• Wolfe compares the current approach to infectious epidemics to the treatment of cardiovascular disease in the nineteen-sixties. At the time, doctors could do little more than wait until heart-attack or stroke victims were rushed to the hospital, and then do their best to keep them alive. As our knowledge of factors like diet, smoking, and blood pressure deepened, the emphasis shifted largely from treating heart disease to preventing it. “When you know what the risks are, then your job is to lower them,’’ Wolfe said. “And with viral epidemics we are beginning to know what the risks are. Yet, by the time we mobilize, it is invariably too late. Look at H1N1”—the 2009 influenza pandemic that infected as many as ninety million people in the United States alone and hundreds of millions throughout the world. “Since the strain turned out to be unusually mild, people said we made too much of a fuss. There was the sentiment—I have heard it expressed numerous times—that the public health service overreacted by trying to vaccinate as many people as possible. That’s wrong. Wrong. Wrong. Wrong.” Wolfe’s voice rose half an octave with each word. “They did exactly what they should have done, and even that didn’t help much. If H1N1 had been more virulent, it would have killed millions of people. Maybe tens of millions. Once it got out there, that thing burned right through the forest. We caught an amazingly lucky break, but let’s not kid ourselves. Luck like that doesn’t last.
• Wolfe continued his soliloquy for much of the trip into the jungle—even after an unfortunate pit stop notable for a painful run-in with a column of red ants. To reach Ngoila, we had to cross the Dja River the only way possible: by ferryboat. Instead of an engine, however, the pilot relied on an elaborate pulley system and on the willingness of passengers to haul on the rope themselves. The crossing may well have been the highlight of Wolfe’s week: he joined the tow line and guilted me into pulling, too. We made it to Ngoila as darkness fell.
• After a restorative meal, Wolfe said it was time to look for bats, noting that they were among the most dangerous viral reservoirs on earth. At that, he and I marched into the pitch-black forest, accompanied by several members of his team and the thunderous honking of Epomops bats.
• Most virologists spend their working lives in laboratories, looking at slides, focussing on specific proteins and, often, on a single disease. Nathan Wolfe’s life conforms more to the pattern of a nineteenth-century explorer than to that of a twenty-first-century biologist. Instead of big game, however, Wolfe’s trophies are viruses. A fastidious man who shaves his beard to a rough stubble every few days (and does the same thing to his head every few weeks), Wolfe has an office in San Francisco, where Global Viral Forecasting is based, and another at Stanford, where he is the Lorry I. Lokey Visiting Professor in Human Biology. He spends at least half his time in California but doesn’t seem entirely at home there—unless the conversation turns to infectious diseases. Then Wolfe is all in. He can talk for hours about hemorrhagic fevers, river blindness, the Barmah Forest virus, and malaria—which, he will be happy to tell you, once nearly killed him. Wolfe finds the idea of the virome—the collective genetic structure of every virus on earth—so captivating that he once described the world to me as a place that consists almost entirely of “bacteria, parasites, and viruses,” adding that “animals really have to be seen as a tiny little addendum.” The undergraduate seminar he teaches at Stanford each spring, on the ecological significance of microorganisms, is called Viral Lifestyles.
• A few decades ago, Wolfe’s microbial obsession would have been considered eccentric. The victory over communicable diseases seemed assured. In 1967, William H. Stewart, the Surgeon General, told a gathering of health experts at the White House, “It is time to close the books on infectious diseases.” That statement was not wholly without justification. In the West, at least, polio, typhoid, cholera, even measles—all major killers—had essentially been vanquished. Smallpox, which was responsible for the deaths of more people than have died in any single war, soon disappeared.
• Since then, however, at least fifty dangerous new viruses have passed from animals into humans. Some are so well known that their names are enough to make people anxious: Ebola, sars, avian influenza. There are dozens of other diseases, like Lassa fever, brought on by a disabling hemorrhagic virus first discovered in Nigeria two years after Stewart’s testimony, as well as those caused by the Nipah, Hendra, and Marburg viruses, which are less frequently mentioned yet just as frightening. These illnesses are called zoonoses—diseases that pass to humans from animals.
• Wolfe is determined to break this pattern of disease transmission, which began ten thousand years ago, with the rise of agricultural communities and domesticated livestock. In 2008, with funding from Google.org, the Skoll Foundation, the Department of Defense, the National Institutes of Health, and others, he founded Global Viral Forecasting, with a goal that was both remarkably simple and stunningly ambitious: to detect pandemics as they begin and stop them before they spread.
• Wolfe and his rapidly expanding team of researchers have created an extensive network of viral listening posts in the villages of Central Africa, and they have compiled a registry of viruses in many other places where pandemics often start: China, Malaysia, Madagascar, and Laos. In the past decade, the group has collected more than a hundred and fifty thousand blood samples from hunters and their families, as well as from the animals that they kill, butcher, and eat. The scientists screen the samples to determine whether any humans have been infected with viruses that came from animals. Virologists refer to the activity of viruses as they leap from animal to man as “viral chatter.” Wolfe and his colleagues monitor samples for early warnings of an epidemic, just as, he often says, analysts “at the National Security Agency scour the Internet, listening for clues of impending terrorist attacks.”
• When Wolfe is in the field, he functions more as an anthropologist than as a biologist. The institute tries to keep track of hunters in scores of villages throughout Cameroon, the Democratic Republic of Congo, Gabon, and other countries. Outreach teams offer health-education classes and collect blood and tissue samples. This program, called Healthy Hunters, is pure social work. It isn’t easy for a foreigner (or anyone else) to tell rural Africans how to conduct their lives. Customs vary widely. “On one of my first visits to a village site in Cameroon, I was with my ex-wife,’’ Wolfe recalled recently. “When we arrived, the chief looked at her and asked me, ‘Ça c’est pour moi?’ It took a second for me to get what he was asking.’’
• The team tries to put local scientists out front and never to arrive in a village empty-handed. Before we left Yaoundé, Wolfe helped load a dozen soccer balls into the back of a Land Cruiser. It is virtually impossible to drive by a field in Cameroon without seeing a group of boys kicking something around—fruit, rolled-up wads of cotton, sometimes an actual ball.
• Everywhere Wolfe and his colleagues go, they stress, in graphic detail, the critical point that primates are not for eating. They long ago learned not to push or proselytize. Hard sells backfire—and usually aren’t necessary. In Central Africa, where people live in wattle huts and dine on bushmeat, viruses like Ebola and H.I.V. are not vague or distant horrors. They are present always, like an endless war, killing neighbors and destroying lives.
• The institute’s research has yielded disturbing results. In October, a group that included Wolfe published a report demonstrating that human parvovirus 4, which was thought to spread solely through shared needles, is far more prevalent in sub-Saharan Africa than had previously been believed. Needles and blood transfusions couldn’t possibly account for all the cases. More ominously, working with researchers from Cameroon and the Centers for Disease Control, in Atlanta, Wolfe discovered that the simian foamy virus, which is endemic in Old World primates, infects one per cent of those who come into regular contact with gorillas and other monkeys. That amounts to thousands of people walking around Cameroon with a retroviral infection that may or may not lead to illness. Before the study was published, the virus, which earned its evocative name because cells infected by it look foamy under a microscope, had never been known to pass between wild animals and hunters. None of the people infected with S.F.V. have shown signs of sickness. Yet, as H.I.V. has demonstrated, it can take years for a retrovirus to cause symptoms of a disease.

“His Highness is changing his relationship status.”

• Wolfe hopes to create a database containing genetic information from those viruses, a resource that biological engineers could use to assemble effective vaccines from standard molecular parts. Building such vaccines, while a long way off, is a fundamental goal of synthetic biology. American bioterrorism experts have shown particular enthusiasm, though: any process that might protect humanity from natural viruses could also be deployed against viruses made by man. (This is just one reason that the Department of Defense and other federal agencies have been highly supportive of Wolfe’s research.) “The more we learn about how these viruses are transmitted to humans, the more likely we will be able to stop them,’’ Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said. “It is always better to prevent a disease than to treat it.”
• Detecting viral pandemics before they spread will be hard; responding to them before they spread will be harder still. “When it comes to understanding the origins of human diseases, you would be surprised how little we know,” Wolfe said. “Where do the major diseases come from? How does a particular virus make the transition into a human host? Is it influenced by certain types of behavior or certain parts of the world? Why are some viruses so much more deadly than others? We have no answers for many of those questions.” Even if scientists succeed in identifying new viruses before they escape into the wider population, pandemics won’t disappear. “We know a lot about heart disease,’’ Wolfe said. “But it still kills thousands of people every day.”
• Like snakes, viruses have a reputation as malevolent, poisonous, and deadly. In fact, most snakes are harmless, and dangerous viruses are rare. In order to inflict serious harm, a virus has to clear several biological hurdles. First, it has to remain unrecognized by the human immune system—to evade any protective antibodies. The virus would also need to make humans sick. (Most do not.) Finally, it would have to spread efficiently—for example, through coughing, sneezing, or shaking hands. Many viruses fulfill one of these criteria; some fulfill two; far fewer meet all three. “Look at H.I.V.,’’ Wolfe said. “We would have to call that the biggest near-miss of our lifetime. Can you imagine how many people would already have died if H.I.V. could be transmitted by a cough?”
• Viruses mutate rapidly, particularly in comparison with the glacial pace of human evolution. What seems benign one day can become deadly the next. Cold viruses are usually considered little more than nuisances, but sars, a virus from the same family as many colds, is lethal. So is avian influenza. “When it comes to predicting what a virus will do, we don’t even know what it is we need to learn,” Wolfe said. “We are really just at the beginning.”
• He continued, “There was a moment in the nineteenth century before we had charted all the mammals in the world, and we found so many new species that people would say, ‘Oh, gosh, we will never document the diversity of animal life on this planet.’ And with mammals that now seems silly, because you would have to search your entire life to find a new primate. That early moment of discovery is where we are now with viruses. . . . I don’t want to oversell it. But in theory, at least, the recipe is simple. You plug the dangerous viruses into some sort of vaccine pipeline. Get all the vaccine parts lined up, put them together, and get them to the people.”
• Wolfe’s optimism is easy to embrace. Nonetheless, the barriers to achieving control over our biological surroundings are daunting. “I won’t say viruses can be conquered,’’ David Baltimore told me. Baltimore, the former president of Caltech, received a Nobel Prize for his work in elucidating the mechanics of retroviruses. “Not completely. But they don’t have to conquer us, either.”
• The morning after we arrived in Ngoila, Matthew LeBreton, the ecology director of Global Virus Forecasting, stood in a laboratory in the back of the group’s spare but well-equipped outpost. He slipped on a surgical smock, a pair of latex gloves, a face mask, and safety glasses. Then he picked up a live fruit bat and dangled it at arm’s length. There are three dozen species of bats in southeastern Cameroon. LeBreton can identify all of them. Bats are well known for transmitting rabies, but they carry other debilitating microbes as well; fruit bats, for example, are believed to be the principal source of the Ebola virus. “The more you know about bats the more you are going to know about viruses,’’ LeBreton told me as he laid the chocolate-brown specimen on a digital scale. “We try to process them carefully and often.”
• LeBreton took urine and fecal samples from the bat. He worked deliberately, but with speed, spreading the bat’s wings and pricking them to obtain a blood sample, which he deposited in a vat of liquid nitrogen. He then turned to me and said, “Now we set the bat free.’’
• Later that morning, we drove to Mbalam to watch Joseph Diffo, who was born in a similar Cameroonian village, discuss the dangers of bushmeat with local hunters and their families. Diffo has a master’s degree in zoology and has worked with G.V.F. as a wildlife technician since 2004. He serves as the site coördinator for field sampling and hunter-education programs. The hunters had gathered early, settling into couches and armchairs that they had dragged to the village square. Diffo, a husky man in blue work pants and a red checkered shirt, passed around a sheaf of photographs. The group suddenly became quiet.
• “Do you see that boy?” Diffo asked, pointing to a recent picture of a local child whose face and body were covered with the type of blistering lesions that for centuries were the hallmark of smallpox. “Why do you think he looks like that?” Nobody answered—but any of them could have. “His father found dead monkeys lying in the forest,’’ Diffo continued, speaking in French. “He brought them home to feed his family.’’ At least one of those animals had been infected with monkeypox, which, while milder and less contagious than smallpox, can be deadly. “If you see a group of animals lying in the forest, do not pick them up,’’ Diffo said. “Whatever killed them can kill you.” It is a message that Diffo repeats constantly as he passes through the villages of Central Africa. He comes armed with gruesome pictures of dead primates, posters explaining the health dangers posed by hunting bushmeat, and bars of soap for people to use after killing or butchering their prey.
• The audience was receptive; the repulsive pictures seemed to have an impact. Everyone collected a large bar of soap, and none of the questions the hunters asked were hostile, exactly. “What can you get us to replace this meat?’’ one of them asked. Killing primates may be dangerous for society and ecologically ruinous, but his children still needed to eat. “We don’t have anything else to give them,’’ he said.
• Diffo cast a worried glance at Wolfe, who was watching from the side. “We know that,’’ Wolfe said. “And we’re working on it. But there is no easy way out.”
• Nathan Wolfe’s first obsession was with chimpanzees. “I always loved them,’’ he told me one evening, while we sat on the veranda of our hotel in Yaoundé, where his Cameroonian operations are based. “I spent years thinking about nonhuman primates, and there came a moment, in college, when I realized that, no matter how often we claim otherwise, humans are not the center of the world. We are players in a much bigger and more compelling drama. A lot of my work is just an attempt to figure out what that drama looks like and where, exactly, we do fit in.”
• In the early nineteen-nineties, while studying as an undergraduate at Stanford, Wolfe became interested in the self-medicating behavior of animals, and the fact that, as he later wrote, “not all pharmacists are human.’’ Many species use plants as medicine in much the same way that we do. Kodiak bears routinely chew the root of Ligusticum, an herb more commonly known as bear root. They spit the juice onto their paws and massage it into their fur; researchers suspect it acts as an antibacterial agent. Birds also use plants as drugs, and they even appear to treat themselves with ants, in a procedure known as “anting,” rubbing them vigorously through their plumage, until the ants secrete protective chemicals. (Wolfe’s interest in self-medicating behavior is not wholly dispassionate. About a year ago, he switched from cigarettes to the Ploom—a high-tech nicotine-delivery system. To “ploom,” one drops an aluminum pod of tobacco into the chamber of a Plexiglas cigarette holder that looks like it was designed for George Jetson. The Ploom delivers a measured, vaporized dose of nicotine, without tar or other cancer-causing chemicals. Wolfe loves to light up in restaurants and theatres, and since no smoke escapes, nobody notices. “It’s a total win-win for me,’’ he said, between puffs on the strange device, which was invented by friends of his from Stanford. “Direct delivery of nicotine without the risk of death.’’)
• Wolfe spent his junior year in the zoology department at Oxford, where he steeped himself in the theories of a longtime hero, Richard Dawkins, as well as in the work of other evolutionary biologists. After graduating, Wolfe began doctoral studies at Harvard, under the guidance of the British primatologist Richard Wrangham and the noted neuroscientist Marc Hauser. Wolfe intended to continue his exploration of the primate medicinal armamentarium, but Wrangham wasn’t encouraging. “He said that learning how chimpanzees medicate themselves would make a perfectly interesting thesis,’’ Wolfe recalled, “but to have an impact you are going to have to understand the underlying infectious diseases.’’ Wrangham told Wolfe that he needed to become an expert in viruses and parasites.
• Soon, Wolfe says, “I got completely hooked on viruses. It is an area of ecstatic ecological complexity.” While in graduate school, Wolfe spent several summers in Uganda, where each morning he foraged for dead mosquitoes among the feces in gorilla and chimpanzee nests. “Not so glamorous,’’ he said, shrugging. “But I was trying to find viruses in their blood. The idea was to get mosquitoes after they had had a blood meal. I think I got about five.”
• At the time, Wolfe was married to a social anthropologist he had met at Harvard. They argued energetically, but not in the way other people argue. “I was completely enamored with the idea that the best way to look at human behavior was to look at the behavior of animals,” Wolfe said. “I believed in evolutionary psychology. She was a complete postmodernist.’’ He forced the last two words out of his mouth as if they were razor blades. “We had fundamentally different views of the nature of human behavior. I would always say, ‘At the end of the day, we are just animals with some nice frosting on top.’ This drove her crazy. She was interested in how unique we are. The fights got pretty intense.” Divorce may have been inevitable—but it took a while. First, she received a grant to study in Thailand, and Wolfe followed her, moving from Harvard to Borneo.
• Wolfe’s job there was to rescue orangutans that had become stranded in isolated parts of the forest where they could no longer survive. He would shoot the animals with tranquillizer darts, then move them to a reserve where they would be safe. Wolfe was also able to do research for his doctoral dissertation, on pathogens found in orangutan blood. “If you are trying to figure out what out there can infect us, then looking at apes makes a lot of sense,” he said. “They have virtually the same physiology as humans—but live in these incredibly diverse terrestrial ecosystems. And they are up to their eyeballs in the blood of different types of animals.”
• One day, he received a message from his mother saying that an Army officer named [Dr. Donald Scott Burke (born 1946)] was looking for him. Burke, the chief virologist at the Walter Reed Army Institute of Research, in Silver Spring, had met Wolfe at a public-health conference the year before, and the men had spent hours talking about their shared obsession with viruses. Burke’s job, loosely defined, was to keep the United States Army safe from epidemics. For practical reasons, the military has always made the control of tropical diseases a priority. Malaria, for example, has often caused more sickness and death among soldiers than bullets or bombs have. In 1943, in the midst of the Pacific campaign, General Douglas MacArthur complained, “This will be a long war if for every division I have facing the enemy I must count on a second division in hospital with malaria and a third division convalescing from this debilitating disease!”
• In the nineteen-eighties, [Dr. Donald Scott Burke (born 1946)]'s studies of H.I.V. prevalence among military recruits were the first to provide a meaningful snapshot of the epidemic in the United States. The Pentagon wanted an aids vaccine urgently, and Burke was asked to direct the effort. He started by exploring genetic variations within the virus itself. As with many infectious agents, including polio and influenza, H.I.V. comes in several strains. A vaccine that will work for one will not necessarily work for all. Distinct regional variations are common: a single strain, for example, has been predominant in Europe and the United States, another in South Africa, and still another in Southeast Asia.
• As [Dr. Donald Scott Burke (born 1946)] studied the data, however, he saw something remarkable. There was one place where every strain of H.I.V. could be found: Central Africa. “If you looked at Cameroon and Gabon, you would see the roots of the epidemic,’’ Burke said. “But nobody had any idea why.” Burke, who is now the dean of the school of public health at the University of Pittsburgh, decided to investigate further.
• Virologists and medical anthropologists had long known that chimpanzees and other apes carry viruses similar to those which infect humans. That’s hardly surprising, since those animals are our nearest evolutionary relatives. Still, nobody had made an explicit connection between the diseases of nonhuman primates and aids. “I certainly had never heard the word ‘bushmeat’ before I went to Cameroon,’’ Burke told me. “Let alone the possibility that bushmeat was associated with the emergence of viruses.”
• [Dr. Donald Scott Burke (born 1946)] made his first trip in 1996, at the invitation of Colonel Eitel Mpoudi-Ngole, a warm, garrulous man who ran the country’s aids program, and who was commonly referred to as Colonel sida—the French acronym for aids. “You did not have to spend much time watching people hunting chimps to understand that this was very clearly a possible route of exposure,” Burke said. “There was blood everywhere, and no precautions taken by the hunters or their wives.”

“Don’t be silly—mathematically, there will always be a middle class.”

• [Dr. Donald Scott Burke (born 1946)] and Mpoudi-Ngole selected fifteen linguistically and geographically diverse villages in locations across Cameroon where they could test the blood of people who came in close contact with animals, particularly primates. It may now seem like an obvious undertaking, but essential ideas are often obvious only in retrospect. When I met Mpoudi-Ngole in Yaoundé, he told me that, by drawing attention to that link, Burke had done more to improve the health of Africans than had any other person alive.
• [Dr. Donald Scott Burke (born 1946)] asked Wolfe to run the operation. Wolfe agreed, but told Burke that he wouldn’t be free for at least a year. Burke said he would wait. “That may have been my best scientific decision,’’ he told me, only partly in jest.
• Wolfe lived in Yaoundé for five years, beginning in 2000, and says he loved every minute of it. He clearly feels at home there. Social skills are as important as scientific prowess to someone who spends so much of his life moving from one research outpost to the next, and Wolfe has a knack for management. He has been able to recruit prominent scientists who are devoted to him. “Nathan inspires me and he inspires everyone we work with,’’ Joseph Fair, the organization’s chief science officer, told me when I met with him in Yaoundé. Like others on Wolfe’s team, Fair left a lucrative job to join the effort—and has never regretted his decision. “We work fifteen-hour days and on Saturdays and Sundays, and you do not get people to do that if they are not enthusiastic,’’ he said. “Nathan makes people feel very good about what they do. Nobody leaves.” (In 2008, Wolfe made a similar choice, walking away from a tenured position in epidemiology at U.C.L.A. to become a full-time virus hunter. “Try explaining that one to your Jewish mother,” he said.)
• We had come to Yaoundé to attend a meeting of military leaders and health officials from several Central African countries. The subject was pandemic preparedness. Wolfe, Fair, and the rest of the team were out every night, listening to West African music and eating tilapia, fufu, and cassava with friends and any number of Army generals. Wolfe was clearly the event’s main attraction, and he was treated with deference by military officials from Cameroon, Equatorial Guinea, Gabon, and Congo—people who rarely agree on anything.
• “Hey, let’s go look at some blood,” Wolfe called, summoning me to what has to be the coldest laboratory in West Africa. The institute—a series of fortified bungalows—sits in the middle of a secure camp on the grounds of the Cameroonian Military Health Research Center, in central Yaoundé. It doesn’t feel particularly military, though—or, for that matter, secure. Just a few hundred yards away, scores of merchants—who seem to have cornered the global market on extension cords, plug adapters, and USB chargers—sell their wares along the wide avenues of the capital.
• The health-research complex has its own water supply, a liquid-nitrogen plant, and a series of freezers set at minus eighty degrees Celsius—an ideal temperature for preserving tissue specimens. Wolfe stood in the middle of a row of cylinders, each filled with cryogenically preserved samples of blood and tissue, taken from hunters, bats, cane rats, gorillas, spot-nosed monkeys, chimpanzees, and scaly anteaters.
• Looking Californian in a maroon sport shirt and sneakers, he quickly unscrewed one of the cylinders. A gust of nitrogen vapor swirled out. The specimens in these containers make up perhaps the most comprehensive library of human and animal blood work in Africa. Hunters throughout the country now routinely carry filter paper, and when they kill a wild animal the hunters deposit a few drops of blood on the paper and seal it in a baggie (provided by G.V.F.). They can send the sample to the lab or wait until somebody comes to collect it. The idea arose from a method used by Matthew LeBreton to preserve dead snakes. “Everybody kills snakes. It is almost a reflex for humans,’’ LeBreton told me. For years, he travelled the length of the country, compiling what would become the definitive book on the reptiles of Cameroon. “I would go to villages and ask people to just throw them in a pot of formalin, which preserved the snakes until I could collect and catalogue them.’’
• Neither LeBreton nor Wolfe believes that it pays to be too picky about the specimens they obtain. “You do not wait for perfection,’’ LeBreton told me. “When . . . we work with bats, we can get specimens into liquid nitrogen in the field. You can’t get better specimens. They are frozen instantly. But it is critical for our work that we not wait for something to be perfect. Because it’s never perfect.’’
• The blood samples have already provided enough data for scores of scientific publications. Last year, scientists relied on the G.V.F. registry to identify the source of Plasmodium falciparum, the form of malaria that has probably killed more people than any other living organism. The origins and the evolutionary history of the parasite have always been murky. Because malaria is so widespread among humans, and so deadly, for years the most common scientific theory held that humans passed the disease to other primates. To test the hypothesis, Wolfe, Stephen Rich, of the University of Massachusetts, and others examined the genetic structure of a hundred samples of the chimpanzee version of the malaria parasite—P. reichenowi. They identified eight strains that collectively were far more genetically diverse than the human form. In fact, P. falciparum could, in most cases, be constructed from the genes of the chimp virus. That could only mean that the human form came from chimps, not the other way around.
• Wolfe’s team has also used its blood samples to search for variants of a virus called H.T.L.V.—human T-lymphotropic virus—which infects millions of people and causes leukemia and neurological illnesses. There had been two known strains—H.T.L.V.-1 and H.T.L.V.-2—and researchers found evidence of both viruses in the primate blood samples; they also discovered two new viruses, which they named H.T.L.V.-3 and H.T.L.V.-4. “This is an astonishing array of viruses,’’ [Dr. Donald Scott Burke (born 1946)] told me. “We have no idea how easily those viruses adapt to humans. Or how easily they can be transmitted between humans. But we better get prepared. Because, frankly, what we already know should be enough to frighten us all.
• This year, Wolfe joined with a team of African, French, and American researchers to report a twentyfold increase in the incidence of monkeypox in Congo since the early nineteen-eighties. At first glance, the results were inexplicable. Then a pattern emerged: Vaccinia, the vaccine used so successfully to eradicate smallpox, also protects against monkeypox. After the last known case of smallpox occurred, in Somalia, in 1977, however, the virus was considered officially eradicated. In most countries, the vaccinations soon stopped, and when they did, a critical line of defense against monkeypox was lost. “The eradication of smallpox is one of the triumphs of medical history,’’ Wolfe said. “But nothing in biology is simple.
• Wolfe sat atop a freezer and dangled his legs like a schoolboy. The monkeypox finding was particularly gratifying to him because it demonstrated the unforeseen complexities of biological systems. “There is a thought experiment that I like,’’ Wolfe said. (“Thought experiment” is a phrase he uses often.) “Let’s just say you had a light switch on the wall and you could flip that switch and destroy every virus on the planet. Would you flip that switch? Almost everyone would say yes. But the effect on the planet would be so profound that life as we know it would cease to exist.” Wolfe may be the viral world’s most vigorous apologist, but he isn’t wrong. Viruses can kill, yet they are also essential. In fact, vaccinia, which defeated smallpox, is itself a virus closely related to cowpox. In some parts of Japan, there have long been high rates of infection with H.T.L.V.-1, which can cause leukemia. People who are infected with that virus, however, are far less likely to develop stomach cancer than those who are not. In a study that followed a thousand people, participants were two and a half times as likely to develop stomach cancer if they were free of H.T.L.V.-1 than if they were infected.
• Bacteria, the dominant life form on earth, are often controlled by viruses. They help regulate marine photosynthesis, and without them there would likely be no algae and no fish in the sea. In fact, earlier this year a team of researchers from M.I.T. managed to program viruses to mimic the process by which plants use sunlight to manufacture the chemicals they need to live. “The reason we think of viruses as negative entities is that physicians are the drunks looking under the lamppost for their keys,” Wolfe has written. “If you are just looking for negative viruses, that is all you are going to find.”
• On a good day, a hunter in Messok-Messok, a dense jungle settlement not far from Ngoila, straggles home with an antelope slung over his shoulder. Or a cane rat. Monkeys, chimps, and gorillas are disappearing, so they are increasingly hard to find. But every so often somebody gets lucky. Late one afternoon, a village man walked into town carrying the body of a crowned monkey, which he turned over to his wife, a pregnant twenty-two-year-old named Sandrine. She laid the crowned monkey, so called for the soft tuft of white hair spread across its skull, on a mat of bright-green palm fronds that she had placed on the floor of the hut. Then she grabbed her machete. With practiced speed and impressive precision, Sandrine slit the monkey’s gut, reached in, and pulled out its intestines. The ground was soon drenched with blood, and so were her hands. Wolfe, LeBreton, and I stood ten feet away, with several members of their team, who were wearing gloves and waiting to collect tissue and blood samples. As the young woman quartered the animal and sliced off its tail, the scientists pulled their face masks tight. I asked Wolfe if he ever offered such precautions to the villagers, and whether it bothered him to see this woman risk her life.
• “Of course it bothers me,’’ he said. “But here are the choices: We can do nothing. We can try to blend in and work without masks or gloves. I won’t allow my people to take those risks. If you are asking if this is fair, then the answer is hell no. But it is not possible to get hunters and their wives to wear gloves. We try to convince them not to butcher if they have cuts on their hands.
• “The bigger question is what can we do for these people?’’ he went on. “How can we help them change their lives? Gloves are going to solve nothing. These people need economic opportunities and agricultural choices.” (One of Wolfe’s colleagues, a medical anthropologist, is working on just this issue. With support from U.S.A.I.D., she is attempting to determine the best way to change the behaviors that cause so much risk.) He pointed to Sandrine, who stood examining her work in the soft afternoon light. “She knows that this is risky,” he said. “But it is not as risky for her as all the other choices in her life. We can worry all we want about viral pandemics, but that is not what keeps her up at night. She needs to care about dinner. And, until we recognize that, the rest means nothing.”
• There are no cell-phone towers in this part of Cameroon. No money. The best roads are mud paths cut by logging companies to move massive and ancient trees, some of which are so large that specially constructed trucks are required to cart them out of the jungle. Wolfe realizes that modern technology and globalization have connected viruses to humanity in dangerous ways, but he also sees in them an opportunity. “The forces that drove us into the age of pandemics can also help prevent them,’’ he said. G.V.F. has started to focus on mobile communications—Wolfe considers the accumulation and analysis of “big data’’ a crucial advance for epidemiology. He recently hired a Stanford medical student, Lucky Gunasekara, who has a background in mobile technology. The team wants every hunter to have a phone. If somebody is feeling sick, or finds five dead gorillas in the forest, or if a doctor sees an unusual rash, a text message can get that information out at once. Viral listening posts won’t work unless villagers are able to share their knowledge. “If Twitter can predict movie sales or stock-market movements, and Google searches can show us where the next flu outbreak will be, surely we can find tools to help this woman,’’ Wolfe said. “If we connect these people more carefully to the larger world, we could begin to address many of these problems.”
• Sandrine had just finished preparing the meat for dinner. I asked her if she understood how risky it was to plunge her hands into the intestines of a dead monkey. “Yes,” she said. “I know that bushmeat is dangerous. That it can kill my children.” She was also aware that there had been an outbreak of Ebola recently in Congo. I wondered whether she or her husband had ever seen dead monkeys or gorillas in the forest. She nodded, gazing at the dark foliage as night began to fall.
• “What did you do when you saw them?” I asked.
• She turned to me and smiled. “I thanked God, picked them up, and brought them home for dinner,” she said. 

• TERRY GROSS, host: This is FRESH AIR. I'm Terry Gross. My guest is virus hunter Nathan Wolfe. He's conducted research in viral hotspots like Central Africa, where the HIV virus began spreading. He studied how viruses like HIV, monkeypox and the so-called bird flu jump species from animals to people. He helped discover new viruses that jump species when hunters killed and butchered non-human primates. He's also studied hunters who were exposed to the blood and body fluids of monkeys, bats and wild pigs. He warns that viruses hitchhike with travelers, so that we should be prepared for viral epidemics that in earlier years would have been contained in small villages. His goal now is to stop pandemics before they start, or contain them once they get going. He's the founder and CEO of Global Viral Forecasting, and is a visiting professor at Stanford. In 2005, he won the National Institutes of Health Director's Pioneer Award. His new book is called "The Viral Storm: The Dawn of a New Pandemic Age."
• Dr. Nathan Wolfe, welcome to FRESH AIR. It's not quite flu season yet, but it is flu shot season, and one of the first stories you tell in your book is about how the H5N1 bird flu began in a village in Thailand. This was a couple of years ago. Would you describe what the first patient was and how he got sick?
• NATHAN WOLFE: Yeah, this was a young boy. His name was Captain. He lived in a - just a small village in Northern Thailand, an area that I've spent some time in myself. And basically, what had happened was he was - he had always been playing with his grandfather, and he had been hanging out with his grandfather. And one of the things that happened that year was that a number of the chickens in the chicken farm that his grandfather had had died. I mean, just like he would have done anytime, he wanted to help out with the tasks. This was sort of what he did as a young boy. And he carried some of the sick chickens during the outbreak that they had. A few days later, he came down with a - quite a severe illness, and it went back and forth. Eventually, his father ended up taking a long drive to take him to one of the big city hospitals, and sadly he died. And he was the first real death that that country had from H5N1, which we think of as the bird flu, we know as the bird flu.
• GROSS: So he got sick from carrying a sick chicken.
• WOLFE: That's right. That's exactly what happens. And if we think about the vast majority of these pandemics that we're experiencing, almost all of them start from an animal virus, an animal microbe that jumps over to humans. And that's actually the same with most of the major diseases of humanity. These things actually start with animals.
• GROSS: And you say virtually all human flu viruses originate in birds, even though we don't call all of them bird flues.
• WOLFE: That's absolutely the case, and it's sort of one of these - at least for virologists - a fascinating situation, where you have - it's actually interplay of a couple of different animals. So most of the diversity - and we can't say that we know everything about what's out there in nature, but our understanding is that most of the diversity of these flu viruses exist in wild bird populations, and particularly some of these migratory water fowl, things like ducks. And what happens is those have the potential to jump into humans. This happens with H5N1 directly. They also have the potential to enter into other animals that we have around us, things like pigs. And then one of the fascinating things about these viruses, we think of viruses as sort of asexual, in other words, that they don't sort of mix and match their genes. It's just they enter, and they start spreading, and all of the daughters are exactly identical to the mother. But that's not the case. So what happens is you have a particular pig out there, it could get infected with two different viruses from maybe one that's been in humans for a while, one that's from the original reservoir of bird. And they can mix and match their genes and create mosaic daughter viruses that will have completely novel properties.
• GROSS: And that can be really deadly, like you give an example of two different flues. If they combined, it could really be dangerous. Tell us that example.
• WOLFE: Well, I mean, it goes back to - now I'm switching gears to H1N1, what people know as the swine flu - again, a bit of a misnomer for those of us who study these things. But - sorry. Just to take one step back, when I think of these viruses and I watch them spreading around, I sort of, in my mind, envision two little dials. One dial - for some reason, it's always on the right-hand side for me - is how transmissible is a virus, how easy is it to go from one person to another. And on the left is sort of how deadly is it. And you think about these two viruses, H1N1 swine flu, H5N1 bird flu. So H1N1 - incredibly, incredibly transmissible. I mean, this is a virus that went from infection zero individuals to perhaps 10 percent of the human population within a single year. I mean, this is just viral fireworks, absolutely incredible. Now, fortunately, nature handed a virus that wasn't that deadly. On other hand, you look at H5N1, that's a virus that was incredibly deadly, is incredibly deadly, and both of these viruses still exist in humans. And, of course, that one didn't spread around so effectively. So when H1N1 really started going, interestingly, we were interested in H1N1, but we started focusing really closely on the people who had H5N1, and the reason why - and the areas that had H5N1 - was because we were really scared that there would be a recombinant. In other words, these H5 and H1 viruses would come together in a particular human or particular pig. They would mix and match their genes and create one that was off the dials on both of them, something that had the potential to spread and was very, very deadly. And that's, of course, the devastating pandemic we're trying to avoid.
• GROSS: Are you still worried about that? Is that still a possibility?
• WOLFE: Oh, absolutely, absolutely. We're still worried about it. And the thing to remember is when you look at the diversity - so we do a lot of the work in the birds to try to understand the nature of the diversity of these viruses in birds. They have a huge reservoir of these viruses, and these viruses continue to sort of ping us. They continue to trickle out of these bird species into our domestic animals and into humans. And so whether it's the particular combination of sort of H5N1 and H1N1 or some other combination, we're really just sort of shuffling these things up, shuffling these things up and waiting for a royal flush. And it's just a matter of time before we get a royal flush.
• GROSS: What do you know about this year's flu season?
• WOLFE: Well, you know, the good news about this is there are people that follow these things very, very closely, and many colleagues of mine do this, and they - what they do is they'll actually sit down, believe it or not, and they'll plot out the trajectories of what you're seeing in these early surveillance - in sort of clinics around the world, and try to guess what the particular flu strain is going to be like in the coming year. And then they'll actually use that, a fictitious virus, which they've combined information on a number of viruses, to come up with a sort of estimate virus, which really, for the moment at least, is fiction. And that's what they'll create the vaccines based on. It's a really amazing process, and it gets more and more accurate each and every year.
• GROSS: Just curious: Do you get flu vaccines every year?
• WOLFE: I get flu vaccines, and I recommend them. I think this is incredibly, one of the most important things we can do to protect ourselves and also protect our communities and our families is to become vaccinated with flu vaccines, as well as a whole range of other vaccines, and I'm happy to talk about all of them.
• GROSS: Yeah, I want to get into that a little bit later. If you're just joining us, my guest is Dr. Nathan Wolfe, and he's the author of the new book "The Viral Storm: The Dawn of a New Pandemic Age." He's a microbiologist who studies emerging viruses in the hope of preventing new pandemics. He studies and tracks emerging viruses, and he founded Global Viral Forecasting. He also teaches at Stanford. You say most pandemics begin with a virus that's transmitted from an animal to a human. Why is it that most viruses start in a bird or another animal, as opposed to starting in a human?
• WOLFE: Well, this is part of the - I mean, frankly, as a virologist, part of the fun stuff about what we get to do is we're studying a world of organisms, sort of this unseen world that's virtually unknown. We know very, very little about this. Some of these things, like viruses, some of the most diverse forms of life on the planet, we've really only been aware of them for 100 years or so. So it's a very different task than, say, studying primates, where maybe you could spend your life studying them and only, you know, perhaps find one new species. This is something that we find new viruses all the time. Like if you look at your hands, there are a number of new viruses on your hands which we have not yet identified, which are - would be completely new to science. But having said that, we can start putting together the pieces of what's out there, and some of it is really just sort of common sense, if you will. So if you think that every one of these mammal species has a repertoire of viruses that normally infect them, okay, and these aren't static. Things are moving around. It's not just things are moving from animals to humans. Things are moving between different animal species. But if that's the case, then, of course, if you look at humans, domestic animals and wild animals as a group, there's going to be many, many more viruses and wild animals just because there's many more species of those wild animals. And then, of course, the interesting questions become: How do we sort through the different species of wild animals to try to determine where the interesting diversity of viruses resides?
• GROSS: So you've actually studied how viruses emerge from animals into human populations. You've studied this in Central Africa. Tell us what you witnessed in Africa among people who still hunt and butcher their meat.
• WOLFE: Well, when we started the work in Central Africa - and that's now about 12 years ago - we really sat down and said: Okay, what are the different risk factors for acquiring a new virus? How is it that these things - what are the portals of entry that these viruses use to sort of jump over into human populations? And, you know, we literally sat down with a number of different behaviors and tried to rank them. And the one right at the very top of that list was hunting and butchering of wild animals. And, look, it's one of these things - we're often very separated, listeners to this program, when they eat their meat, mostly it'll be served to them in a restaurant, or if they buy it from the grocery store, it's going to come wrapped nicely in Saran Wrap. That's not, by and large, the way that we interacted with meat and we interacted with food historically. It's not, by and large, the way that people in Central Africa and many parts of the world interact with meat. And when you witness hunting and butchering, you recognize what an incredibly intimate biological interaction this is between us and other mammal species and some of our closest-living relatives, some things like other primate species. You're talking about blood which is inevitably all over hands. You're talking about cuts that'll happen on pieces of bone shard while you are removing a particular organ. And I'm sorry for the graphic details here, but the reality is that there's a tremendous amount of contact. And it's not contact with one particular tissue. It's contact with all of the different organs and tissue systems. And sometimes these viruses, even if we look at ourselves, at really any animal, they're not evenly distributed between our different tissues. You know, so if you just have contact with skin, or you just have contact with blood, you're getting just a little piece of the diversity of these things. But if you really hunt and butcher, you're getting the full diversity of contact, and what that means is that the viruses in all those tissues of all those different animals have the potential to jump over. And that's why it's such an interesting behavior and one that we spend a lot of time on.
• GROSS: So you're trying to - are you trying to prevent people from hunting in Central Africa, or are you asking them to use vinyl gloves when they butcher the meat? I mean, what can you do for people whose lifestyle depends on hunting and eating what they've killed and still protect them from being the patient zero, where the, you know, the virus carried by the animal jumps species?
• WOLFE: Yeah, and we're trying to do two things. Obviously, one of the things we're trying to understand is what is jumping over and getting a sense of that, which is of course important for these populations and people all throughout the world. And yes, what we are trying to do is to understand how it is we can go about changing behavior. We're actively sort of working to come up with animal protein solutions. There's wonderful organizations around the world, organizations like Heifer, for example, that we're in active discussions with about ways that we can try to introduce novel sources of animal protein that'll help to allow people to have different, you know, different sources of animal protein so they're not forced to hunt wild game. For the moment, though, I mean, we're there, and mostly our mission is to understand what's crossing over and to try to catch it early. And this is a big, big problem. And you're talking about tens, if not hundreds of thousands of individuals who are depending on wild game as a protein source. So this is something that we're going to need to sort of bump up a notch and get a lot of involvement in and we're all going to need to take very, very seriously if we're going to be able to address this problem.
• GROSS: Now, you've also been asking hunters to collect blood samples of their game. So how are you doing that, and what does it help you do as a virus hunter?
• WOLFE: Yes, of course, in the process of our education - we call it sort of the Healthy Hunter Program - we work hard to work folks into alternatives. But the reality is many of these individuals will continue to hunt wild game. And what we ask them to do is we provide them with just sort of a baseball-card-sized piece of paper. It's special laboratory paper, but it looks like any other piece of paper. And we say if you are going to have contact with us, then we ask you how about just taking a few drops of blood and put it on this paper. And this is sort of the incredible miracle of contemporary molecular biology, is that even if these pieces of paper sit at room temperature for weeks and even months at a time before we collect them, as long as they're dried appropriately, we can bring them back and actually discover not only details about the animal that was hunted, but all sorts of information about the viruses and other organisms that are in that animal. And so it allows us to very quickly come up with an understanding of the diversity of bugs that are out there that have the potential to jump into us.
• GROSS: What's the most important thing you've learned from collecting those blood samples?
• WOLFE: Well, we see new things all the time. We find a diversity of new retroviruses that are out there. So, of course, retroviruses, this is the family of viruses that HIV falls into, and we're very, very concerned. This is the part of the world where HIV jumped from chimpanzees into humans. There's no reason why other viruses in that same class won't have a capacity into humans, and by and large, we don't focus on those. So we've been very, very attentive to those. We've found a number of new retroviruses in these blood specimens. We have identified new species of malaria that are out there infecting these animals that have the potential to enter into humans. And we're really starting to burn through this massive collection of blood spots to understand what's out there.
• GROSS: My guest is Nathan Wolfe. He's a microbiologist who studies emerging viruses and tries to find ways to prevent new pandemics. He's the founder of Global Viral Forecasting and the author of the new book "The Viral Storm: The Dawn of a New Pandemic Age." Let's talk about HIV, which is an example of, you know, a very dangerous virus jumping from animal to human. And the theory that you write about in the book is that chimpanzees contracted the virus by hunting and feeding on a certain species of monkey. And the chimps spread the virus to humans. Is this - do scientists know this for sure, or is this just, you know, one theory among others? 
• WOLFE: Yeah, it's really beyond sort of one theory among others. We know more about the origins of HIV than we do for almost any other virus that affects us or has affected us in history. And it is. It's just the story that you describe. It's about chimpanzees acquiring these new viruses through their hunting behavior, and then subsequently humans becoming infected with this virus through hunting and butchering of chimpanzees. And then it's a virus that's spread around the world. But in some ways, the amazing feature for me is not that chimpanzees acquired these monkey viruses in their environment. We expect that. And it's in fact not really that humans acquired a chimpanzee virus, because since chimpanzees are so closely related to us, of course we're going to have the capacity to be infected with a whole range of the different microorganisms that infect them. What's amazing for me is that this incredibly fundamental and important pandemic - you know, something that we can really think of as sort of a scrape in the skin, in the fabric of humanity, something which has either directly or indirectly affected all of us - that it basically was in humans for 50, 60, 70 years before we even became aware of it. And, you know, I think it's an important question we should be asking ourselves: Are we willing to live in a world where we'll let these things spread around, just waiting for them to go global before we actually catch them? And I think that's one of the things we're really focused on trying to change.
• GROSS: Okay. So you founded Global Viral Forecasting a few years ago, and one of its goals is to stop pandemics, to prevent pandemics. So if your group existed when the HIV virus was first identified, what would you have done to prevent it from becoming a pandemic?
• WOLFE: Yeah. And let me take a step back, because really, what our objective would have been would have been to find it and to really make a serious statement about it. And again, what I can tell you is we continue to find other retroviruses. So had we discovered HIV in a rural village, let's say, in the '60s or '70s, something like that, we would have done what we would have had the capacity with our tools to do at that time, which is we would have studied the epidemiology of that particular virus, just like we're studying the epidemiology of these other new retroviruses that we've discovered. And you might ask, okay, well, what's that going to do? You know, maybe you're not going to necessarily generate a vaccine. You're not going to - well, we would've known how the thing spread. Okay, so in 1981, when the disease was first sort of identified, we didn't know how it was spread. And it happened to be seen first in individuals who received blood products and in gay populations. And so, as a consequence, we took a whole range of wrong turns, and we treated the epidemic in its early sort of global spread in a way that as completely, completely wrongheaded. It took until 1986 before the president of the United States even used the word on AIDS on - you know, in public messages. But we would've known that the virus heterosexually. We would have had the - we would have seen it spread. We would have had the potential to take measures to try to control its spread. As it began to spread more substantially, we would have been thinking about how do we develop vaccines, how do we approach it. I mean, it's the early detection. And the way I think about like early detection, it's a little bit like the power of compounding interest, but only sort of in the, you know, in the converse sort of way. The earlier that we detect these things, the more we have the potential to save lives in the future.
• GROSS: This is FRESH AIR. I'm Terry Gross back with virus hunter Nathan Wolfe. He spent time in viral hotspots like Central Africa, studying how viruses jump species from animals to humans. He's conducted studies on hunters were exposed to the body and blood and body fluids of monkeys, bats, wild pigs and other hunted animals. By collecting specimens from hunters and their prey, he and his colleagues have discovered previously unknown viruses. He's now the CEO of Global Viral Forecasting, which monitors emerging viruses to help stop or contain pandemics. He's also a visiting professor in human biology at Stanford University. His new book is called "The Viral Storm." Now you write in your book "The Viral Storm" that you think pandemics will increase in frequency. Why? 
• WOLFE: Well, it's just - there's this amazing picture that I use in the book and I use in all of my presentations, and it basically shows that the air routes presence in the 30s and 40s and the air routes present around the world in the last few years, and what you see is... 
• GROSS: Air travel, you're talking about?
• WOLFE: Yeah. These are just like the various sorts of connections that airlines make between different points on the planet. And even if you go back 20, 30 years, there weren't that many lines connecting all of us. And if you look now, you see, basically, a plate of spaghetti. I mean there are incredible connections. Airlines and boats are moving humans and animals around the world in incredible way. The features of globalization have huge consequences on pandemics. And the way that this works is it just connects us so much more closely. So one way to think of this is to go back and imagine a virus that jumped over from an animal into a human, you know, say 100 years ago. By and large, there weren't the levels of connections between us, so imagine a rural village in Cameroon, like the kinds of villages we working now, or Democratic Republic of Congo. I mean these would have been villages where the virus would have jumped over, and these viruses have always jumped over. They would've spread to a number of individuals. Those individuals would either have died or become immune, and then it would've reached the end of the line and it would have just gone extinct. And that happened on countless experiences, countless times throughout the history of humanity. Now what happens is those remote isolated villages, rather than the majority, they're increasing the minority. So every one of these viruses that jumps over into humans as sort of a global stage in which to act and these animals are moving around at incredible speeds, we're sort of connecting animals and humans in ways that we've never contacted them before, through the ways that we deal with food. And as a consequence, every one of these viruses that jumps over from animals into humans potentially has the capacity to infect all of us.
• GROSS: So while we're talking about viruses jumping from animals to humans, do people need to be concerned about pets? Because let's face it, pets sleep on people's beds and they're on people's laps and they're licking the faces of the people that they live with. Is that a concern?
• WOLFE: I don't think it's an immediate concern, but I think it's something that we need to think through and be a little bit cautious of. Now, and I spent a lot of time in the book talking about this, which is so the longer we have an interaction with a particular species, the more likely that any of their sort of indigenous microbes that would have the potential to harm us on a global scale would probably have already jumped out. OK? So that means that is there something hidden in a dog, per se, or in a cat that's likely to come out and be devastating to human populations? I would say the probability of that is likely to be very low. Now let's flip that on its head though. These dogs and these cats are not somehow in this biological vacuum of our home and not connected to different animal species. They have the potential to acquire new viruses from different animals and spread. We saw this very dramatically in nipah virus, which is a virus that jumped from bats into pigs. Pigs is domestic animals, of course, and then jumped into humans and had a huge devastating effect. We see this very commonly in influenza viruses, which we talked a little bit about. We see this in a whole range of different things. So could cats or dogs be the sort of unwitting vectors of a virus that could infect them from wild animals and potentially spread in humans? Absolutely. And would this be a huge challenge if it happened? I think it would be a huge challenge, because imagine saying OK, we're going to have to call massive numbers of dog and cat populations and just try to think about how people in the United States, for example, would respond to that. I don't think they would be lining up with their pets in their arms.
• GROSS: I'm just thinking about how you live in a world where the things that are invisible to us are your preoccupation. You know what I mean? Like you're just seeing like viruses all over the place and probably bacteria too. Did I mention fungus?
• WOLFE: Absolutely. No, and I mean look, that's part of the, sort of, fun frankly, of being a microbiologist right now, is we increasingly have the tools where we can understand the nature of this very, very diverse and massive unseen world. And it's - you can't understate how fundamental these are. I often do, sort of, a thought experiment for my students at Stanford, where you imagine, sort of, an intelligent extraterrestrial tasked with writing the Encyclopedia of Life on Earth. And from a human perspective, we're all sort of locked up in this notion of oh, it'll all be about humans and we'd be most of the chapters. Wrong. That wouldn't be the way that they would imagine it. For the vast majority of the history on our planet, microbes were the only organisms that existed. All of life was unseen. And even right now the vast majority in terms of mass and certainly in terms of diversity of life on the planet is represented by these microbes. So they're incredibly dominant and yet, we only for the first time now, have the tools that will allow us to start sort of, if you will, putting on the glasses where we can ignore the macro pieces of life and see the micro in a way that's really, really clear. So it's an incredibly exciting time for exploration and discovery in biology. This is not a world where we've discovered everything that's out there. We're only scratching the surface.
• GROSS: Along the lines, like the ickyist(ph) part of your book I think is describing what you think is on a typical human body - on a typical tabletop, on a typical floor, in terms of microorganisms.
• WOLFE: Yeah. I have to say that if we're honest with ourselves, we should see ourselves really as walking, sort of, symbiotic colonies of human and other life - microbial life. Now, there's...
• GROSS: Describe that a little bit.
• WOLFE: Sure. So OK, if we...
• GROSS: What are you and I carrying right now?
• WOLFE: OK. So let's just take the cells in your body. If we were, let's say we were to count the number of cells between the top of your head and the socks on your feet. What we would find, and this is going to be a little bit counterintuitive, is that 90 percent of those cells are actually not human cells. Ninety percent of those cells belong to, sort of, the various microorganisms that exist, now primarily, in your gut and on your skin, but also in many, many other sorts of parts of your body. There's tons and tons of microbes out there. Now, there's a little bit of a trick there, which is they are actually much smaller than our own selves, so this is not exactly a story of mass, but it is a story of the number of cells. And then if you take diversity it gets even more, you know, if you get wigged out by sort of the number of cells, the diversity is even more amazing. The diversity of human genetic information on our bodies and in our bodies is less than a, you know, sort of a fraction of a percent. Most of the diversity that we're walking around with, most of the biological information actually belongs to the microbial world that inhabits us.
• GROSS: Now you say that if you could kill all viruses of the world, you wouldn't, because some viruses are probably really helpful and could be helpful in ways that we don't even know. So what are some of the really helpful sides of viruses?
• WOLFE: Well, first of all, and I spend a entire chapter in the book, which I call the "Chapter of The Gentle Virus," sort of going through all this and I feel like it's a little bit of my, sort of, evening exercise. You know, if you're going to be focused a lot on the deadly ones you have to also think about the ones that are not deadly. And, of course, most of the viruses, the vast, vast majority, only a small needle in the haystack of viruses out there are things that even infect us, let alone have the potential to harm us. Now when a species like our own, sort of, encounters this massive amount of new life, obviously one of the first questions we're going to ask is, is it harming us? Does it kill us? And that's going to be our preoccupation for some time, but I think very quickly we'll get to the point of saying, you know, what is the diversity of viruses in oceans? And it's absolutely amazing. You take a, just a little teaspoon of the water from the ocean and start documenting the diversity of viruses there, it's huge. And the number of viral particles, absolutely amazing, you know, even in terms of mass in the ocean, they're huge. The notion that all of these things would be harmful to us, of course, is just a, you know, just a terrible human fallacy, number one. And number two, the idea that if you had, you know, if you could again, flip that switch, that's the thought experiment that you're posing here - is you flip a switch, suddenly all the viruses on the planet disappear. The effects, the ripple effects would be so incredibly profound on all of the microorganisms, in the oceans systems, in coral, in sort of soil communities, would be so dramatic that it's hard to say, good or bad, but certainly for us as a fragile little species that's really only existed for, you know, a split second in the history of our planet, we're likely to be very fragile to that sort of dramatic change. And I think that there's every reason to suspect that we would die and probably die out as a species very quickly if we did that.
• GROSS: In terms of putting viruses to work for us, instead of just being victimized by them, you are hoping that there will be more productive research done in how viruses can help cure or slow down cancer.
• WOLFE: Oh, absolutely. And we work closely with the National Cancer Institute. We have a multiyear award from the National Cancer Institute to really, sort of, interrogating tumors and understand the diversity of viruses that are present in them, and I think this is very, very important. Look, obviously if we take a step back, what are the major victories that we've had in cancer? And I'm sure if we had a cancer biologist here they might have a different perspective. But at least as an outsider I see we invest, you know, I don't know what it is. I think the National Cancer Institute, four or five, $10 billion a year and probably NCI and the other organizations, and we're making progress but it's not exactly dramatic progress. But if we look at some of the incredible victories out there, some of these have been viruses. So, for example cervical cancer, right. Cervical cancer is one that has been in the news lately. I mean this is a cancer which is devastating for women, women at often, you know, relatively young ages. Women all throughout the planet have had this. It's something that has been devastating for many, many centuries. All of a sudden we recognize - and this was, you know, subject of the Nobel Prize a couple years back - that it's really a virus that causes the vast majority of cervical cancer. Wow. Boom. All of a sudden we can go out, we can develop a vaccine against the particular virus. That's exactly what we've done. And so the real question...
• GROSS: And you're talking about the HPV vaccine?
• WOLFE: HPV vaccine. Exactly. Exactly. And so basically that's a story of knowledge of a particular virus helping us to solve a major problem in cancer. And actually, viruses - and I talk about this in the book - if we spin smallpox eradication on its head, so you may ask how did we eradicate smallpox? One of the most sort of dramatic successes in the history of human public health, and people will think oh, well, you did that through the smallpox vaccine. OK. Well, what's the smallpox vaccine? Oh, I'm sure that this is the sort of incredible biotech solution that allowed us to - no. It's not a biotech fancy biotech solution. It's basically technology we've had, you know, for a long, long period of time and this was, you know, early research done by Jenner that basically looked out and saw oh, it looks like people who are milkmaids, that are actually milking cows, seem to have a lower propensity for getting smallpox. Oh, maybe it's this virus that cows have that's not deadly enough to humans to cause them to die, but is strong enough to elicit a response so that they don't get smallpox. And it's basically just by taking a variant of this cowpox virus and not even doing, not adulterating it that much and basically spreading it throughout the world that allowed us to eradicate smallpox. Basically it's a virus that allowed us to eradicate smallpox.
• GROSS: So getting back to HPV, so the HPV virus causes a lot of cervical cancer. We had they HPV vaccine now, and that vaccine is at the center of controversy. I mean it's even been discussed and argued about in Republican primary - in a Republican primary debate. So, you know, the question being should be administered at schools? Should it be mandatory? I'd be really interested in hearing your thoughts about that.
• WOLFE: Again, I should emphasize, my expertise is about identifying these pandemics early before they spread, so the policy issues of exactly when to administer them is, sort of, are better left for others. Having said that, look, the wonderful news now is that we have more amazing vaccines than we've ever had in history and these vaccines are safer than they've ever been. When properly given, according to the requirements of the vaccine, these are things that are, you know, are very, very safe and very effective in helping people to prevent a whole range of different illnesses that can harm them and their families.
• GROSS: So, let's take out the controversy over whether giving HPV vaccines in schools is wise or not, and whether it would lead to more sexual behavior or not. That is definitely not your thing. But just in terms of the safety and effectiveness of that vaccine, of the HPV vaccine, what would you have to say?
• WOLFE: Everything that we know about this vaccine is that it will stop girls and women from having cervical cancer, and I think that that's the really, that's the most important part of this debate.
• GROSS: So you are not only exposed to viruses in the United States, you travel a lot to study viruses. You go to places that are the hotspots for emerging viruses and pandemics. What do you do to protect yourself from catching a virus?
• WOLFE: Well, one of the things we do, and we deploy this in all the laboratories we work in around the world, and actually help other laboratories to develop them, is incredible procedures to allow people that work in the labs to protect themselves from dangerous microbial agents and also to catalogue these things better, to create better bio security and to, sort of, improve the way that we approach them. The approach that we use whenever we deal with any of these is what we call universal precaution. So the idea is we've got a blood specimen, most likely that blood specimen, even no matter what animal it came from, is probably not going to be deadly to us, but we treat it as if it is. And as a consequence, were obviously sort of very proud and happy that we've never had an incident where we've had any sorts of problems with any of the folks in our labs, anywhere around the world. Having said that, you know, we certainly encounter these risks. You know, there's risks associated with driving on some of these back roads. There's a lot of risks associated with malaria. I've been infected with malaria a couple of times and it's given me a new sort of respect for how devastating this particular parasitic illness is for the many populations that have to live with it, day in and day out. It is absolutely devastating.
• GROSS: OK. So, when you're traveling or when you're just at home in the United States, do you wash your hands all the time? Do you ever wear a face mask? There's a face mask on the cover of your book, "The Viral Storm." I don't know if that's supposed to be sending us a message or not. And are those alcohol-based hand cleansers, the ones that are in the Purell family, are they effective against viruses?
• WOLFE: Well, I have to say that I am, I'm one of these folks that does not particularly, sort of, I don't have a hypercondriacal bone in my body, which I guess you would imagine would be an occupational hazard if you did something like what I do. But, you know certainly I think that they are, I was asked by the publishers at Holt to put something in there that really sort of spoke to people and talked about what are things that, you know, people reading the book can do. You know, I think that there's a lot of things that people reading the book can do. And one of them is really just to understand the nature of the risks that are present and to be able to sort through the different kinds of risks. For, I was going to say, for better or worse, but I think it's mostly for worse. We had a media environment now that responds to these infectious disease risks, sort of, first off it goes crazy and says there's a huge risk and you have to all be careful. And then if it doesn't end up being as large of a risk as they originally advocated, then they'll turn around and say oh, and the public health officials have completely overblown this risk. I mean H1N1 is a perfect example of this. H1N1, from my perspective was - you know, people got mad at the public health community for saying that this was a really, potentially dangerous risk. But they were exactly right in saying that it was a dangerous risk. You know, that anger is sort of like the anger that you would have had a meteorologist that was following a hurricane headed for, you know, Washington, D.C., and that basically followed it and followed it and, you know, the hurricane veered off course and, but you should the meteorologist for all the preparations you made. That would be crazy. And these pandemics, you have to imagine, it's like a hurricane but it's like the hurricane that didn't last for three days. It's a hurricane that lasted for years. It's a hurricane that doesn't affect just one city but it infects, potentially, the entire planet.
• GROSS: Nathan Wolfe, thank you so much for talking with us. I really appreciate it.
• WOLFE: It was a real pleasure. Thank you very much for having me.
• GROSS: Nathan Wolfe is the author of the new book "The Viral Storm." You can read an excerpt on our website, freshair.npr.org. This is FRESH AIR.

On a weekday morning in mid-summer, Nathan Wolfe walks into Swan Oyster Depot in San Francisco’s affluent Nob Hill neighbourhood. The restaurant has about two dozen rickety wooden stools along an old-fashioned diner-style counter. A wall menu, partly handwritten, looks like it hasn’t changed in decades. If you don’t like raw seafood, you won’t like eating here. But this is Wolfe’s favourite place in town, just down the street from his apartment. He visits it as often as possible, which, he says, “isn’t often enough”.

Wolfe has just returned from a three-week visit to Cameroon and Gabon, where the Global Viral Forecasting Initiative (GVFI), the non-profit organisation he founded in 2008 on the back of funding sources as diverse as the US Department of Defence and Google.org, is doing some of the most important and dangerous virus-detection work in the world.

Wolfe’s trip was a whirlwind of lab visits, conferences with military officials, and, most importantly, specimen collecting in the bush.

A day at the office for Wolfe, when he’s in the field, involves harrowing multi-hour drives to some of the world’s most remote forest areas, where he and his team gather blood samples from African bush hunters and their animal quarry.

These distant outposts, he will explain, are the potential source of the most deadly viral diseases afflicting humankind. By looking for the source, he’s trying to stop the next global pandemic in its tracks before it starts.

Wolfe can “jam on the science” like nobody else, says his GVFI colleague Jeremy Alberga, but he gets just as animated when talking about the adventurous aspects of his life that have led him to be referred to, time and again, as “the Indiana Jones of virus hunting”.

He likes to talk about the time he contracted a rare “collector’s item” strain of malaria that almost killed him, or the apocryphal story of how he and some colleagues were coming out of the Cameroonian bush with some rare blood samples when they encountered a lorry jack-knifed across the road.

There was no driver around, or any sign that someone was coming to clear the accident away. The samples needed to be refrigerated. They wouldn’t be good forever. And they’d spent weeks persuading people to give them. So Wolfe and his colleagues got out and started digging a track around the stranded vehicle with their bare hands so that they could get through.

That’s how Wolfe operates. He knows his way around Central African logging roads like a city-dweller knows a subway map. There’s no predicament too large to prevent him from getting the word out about viruses.

But first, a shellfish breakfast in San Francisco. The staff are getting ready for the day’s lunch rush, mixing up mignonette and cocktail sauce. Wolfe likes this place because of the authentic local feel. In some ways, even though it’s 100 times more expensive, it reminds him of roadside restaurants in Yaoundé, the capital of Cameroon, his home for years and which he still visits often. There, he breakfasts with cab drivers, eating omelettes made with sardines, spaghetti and chillies and cooked in palm oil.

When the staff at Swan see Wolfe, everything stops. Wolfe, 40 and trim, is dressed casually in a sweater and trousers. His hair is buzzed down and he wears a close stubble, which is how he prefers his beard.

“I either have long hair or I shave it all off,” he says. “I’m not an in-between kind of guy.”

“Hey, Nate, how’s it going?” says a bar worker.

“It’s going good.”

“Where you been?”

“Oh, here and there,” Wolfe says.

“What are you in the mood for?” asks a counter guy.

“What’s fresh?”

“We’re catching a lot of local seafood. First time in five years. It’s nice.”

Wolfe decides on a platter of oysters and clams to start. Raw tuna and hamachi will follow, and then an assortment of smoked salmon. That’s a mild meal for him. On his travels, he’s dined on everything from fried grubworm to porcupine, and on up the food chain. “I don’t do primate,” he says.

Nothing, except probably viruses, gets him fired up with more enthusiasm and excitement than food does. In his mind, the two subjects are connected, because viruses often “jump” from one species to another when people — be they hunters, farmers or vendors at public markets with less-than-ideal sanitation — come into contact with animals that they plan to eat. 

“People everywhere in the world eat local wild food,” he says. “That’s the nature of being human. But some people are in places with a lot more underlying viruses.”

Then he says: “I’m gonna have a bloody beer. You want one?”

A “bloody beer”, it turns out, is a house speciality of Swan Oyster Depot. It’s essentially a Bloody Mary — fresh-made tomato juice and a house spice blend, but with beer instead of vodka. Wolfe plans on drinking one before ever setting foot in the office, at 10am on a Tuesday. It’s hard to resist the offer. When you’re with Nathan Wolfe, you do as the locals do.

Even though viruses — tiny, non-cellular creatures that need to infect cell-based lifeforms in order to survive — have been evolving with human beings since we first stepped down from the trees millions of years ago, we’ve only been aware of them since 1921, when a Dutch scientist discovered their existence while studying disease in tobacco plants. 

We still know relatively little about viruses, but we do know that, though the majority of them are relatively harmless (and some are actually beneficial), a small percentage have the ability to make humans enormously sick. And the risks increase exponentially every year. “The nature of how we, as a society, deal with threats from microbes is very much how we dealt with risks for heart disease in the Fifties and Sixties,” Wolfe says. “It’s as if all of our energy was spent not trying to prevent cancer or heart disease, but just focused on chemotherapy and bypass surgery.”

In 1967, William Stewart, the US Surgeon General, famously told a gathering of health experts at the White House: “The time has come to close the book on infectious diseases. We have basically wiped out infection in the United States.” It was, to be sure, an era of medical triumph. Polio, cholera, typhoid fever and even the deadly smallpox virus, had all been defeated, or nearly, in the West.

But the statement turned out to have more than a faint air of George W Bush’s “mission accomplished” comment concerning the Iraq War. In Stewart’s day, dread scourges like Ebola and Sars hadn’t yet made their appearance and HIV was unknown except to a few primate scientists working in obscurity. Despite the Surgeon General’s boasting, the era of viral infection had barely begun.

Since World War II, more than 300 new viral diseases have infected humans. Seventy-five per cent of those are “zoonotic”, meaning they’ve jumped from wild animals. As human life becomes more globalised, it creates a rich, nutritious environment for viral life. Miners, loggers and hunters are coming into contact with wildlife in more remote areas than ever before, but they’re also shipping their wares to densely packed cities. Conditions are ripe for outbreak.

“There is simply no greater threat to humanity than a viral pandemic,” Wolfe stated last year. “What is more likely to kill millions of people? Nuclear war or a virus that makes the leap from animal to man? If, tomorrow, I had to go to Las Vegas and place a bet on the next great killer, then I would put all my money on a virus.”

Though it seemed like the HIV pandemic appeared out of nowhere to plague the world’s urban gay communities in the Eighties, recent findings show that the virus first jumped from chimpanzee to human around 1900. But at the time HIV first appeared, it wasn’t so easy for viruses to get out of remote areas of Africa.

One hundred years ago, human beings were much more isolated, new diseases didn’t travel so easily, thus HIV remained unnoticed for decades.

Contrast that with Sars (severe acute respiratory syndrome). Sars first manifested itself in 2003 when a 48-year-old man from Guangdong province in China, who’d come into contact with the disease at a meat market, fell ill in a hotel in Hong Kong. The virus spread and mutated fast, killing 774 people in Europe, North America and Asia, though it infected thousands more. The World Health Organisation responded efficiently and was able to contain the virus, but that was largely because Sars had spread to countries with well-developed public health systems.

Influenza, the most common form of viral infection, also continues to evolve. When the “Spanish flu” roared around the world in 1918 and 1919, claiming up to 50 million lives, humans had little idea from whence it had come or how to stop it — they simply had to wait for the contagion to burn itself out. 

H1N1, or “swine flu”, struck in 2009 with potentially far more severe consequences. Viral lifeforms have the ability to “reassort”, or to mix and match, genes, to create completely new viruses. H1N1 brought together one strain of human influenza, one from birds and another from pigs, to create a potential “super-flu” that, if the worst-case scenario had been realised, would have made the 1918–19 pandemic look insignificant.

The World Health Organisation estimated it could have infected up to two billion people, one-third of human beings. Though swine flu spread fast, a relatively few 18,398 people died worldwide and a panicked humanity breathed a sigh of relief.

But, says Nathan Wolfe, we may have learned the wrong lesson. Three years after the H1N1 contagion, very little has changed. “We’re not dodging bullets here,” he explains. “We’re dodging things that are much more dangerous than bullets. If someone shoots a cannonball at you and it misses you, you want to understand where it’s coming from.

When you have something that moves so effectively, had it become even nominally more harmful, you would have been talking about hundreds of thousands, or millions, of dead people, easily. We just got incredibly lucky.”

Swine flu should have brought on a critique of the global health system, Wolfe says. “Not that they overreacted,” he continues. “The critique should have been that, despite your best actions, 10 per cent of the human population got infected. What if it had grown more deadly? Then you would have been talking about a massive global disaster. People don’t get that. H1N1 represents the moment, to me, where we take a deep breath and say, ‘Look, we’re experiencing these things. We have to understand where they’re coming from. You’d better know about it; you’d better figure it out. Responding appropriately is good, but we’re going to hold you to a higher standard.’”

Though Wolfe is concerned about keeping people from getting sick, he’s not in the pandemic prevention business. His bailiwick is to explore the originating nature of pandemics, to predict them. He gets the word out any way he can, whether as a scientific consultant to the Steven Soderbergh virus movie Contagion, starring Kate Winslet, Jude Law and Matt Damon, or, now, as an author.

In The Viral Storm, Wolfe argues that though “much hard work remains… we will harness the numerous technological advances of our time that provide tools to predict pandemics – just as meteorologists predict the course of hurricanes – and ideally prevent them from occurring in the first place. This is the Holy Grail of modern public health”.

In the search for that grail, Wolfe is undeniably King Arthur.

***

Wolfe grew up in Detroit, Michigan, the son of social workers. His father was involved in Jewish community services and his mother was a school guidance counsellor. From an early age, he found himself focused on biology. He remembers seeing a National Geographic documentary about primates through which he learnt that humans are more closely related to chimpanzees and gorillas than we are to Old World monkeys, such as colobus, baboons and so on. “That was when I started thinking that I wanted to do science,” he says. “I became fascinated with these animals.” He realised that human beings might not, in fact, be the centre of the natural universe.

Throughout high school, Wolfe studied evolutionary biology and primatology. Though he became “a little bit distracted” by philosophy while an undergraduate at Stanford University in the early Nineties, he got accepted to do a junior-year evolutionary biology honours project at Oxford. “I remember thinking to myself that this was a great way to find out about different places in the world,” he says. His boyhood passion, it turned out, was also the gateway to a life of travel and adventure.

Wolfe’s initial research was on the self-medicating behaviour of chimps; like other animals in nature, they use various plants as natural treatments against diseases. As a doctoral student at Harvard, Wolfe won a slot to study in Uganda with the British primatologist Richard Wrangham, who persuaded him his initial focus was a little off-base. “He said I needed to understand the underlying disease states of the animals to address this question,” Wolfe said. Any study of self-medicating would take years, if not decades, and might never yield results. It was the kind of advice on which a career is built.

Those were unglamorous times for Wolfe, with many hours spent picking mosquitoes out of primate faeces in remote forest areas. Wolfe travelled from Africa to Borneo, where he rescued stranded orangutans and pursued his dissertation work, which involved analysing pathogens found in orangutan blood. Studying apes made sense for him, because they have similar biological structures to humans, but are far more resistant to disease. Just as importantly, they live in regions of greater biological diversity and therefore have more exposure to obscure pathogens.

“The underlying animals that cause these potential future pandemics are not evenly distributed around the world,” Wolfe says. “Here in San Francisco, I’m not saying we don’t have some interesting biodiversity. But if we see something brand new here, it originated somewhere else.”

Wolfe began to build a reputation in the highly specialised world of virology. In the late Nineties, while working in Borneo, he received a message saying a “man from the military” was looking for him. That man turned out to be Dr Donald Burke, the chief virologist at the Walter Reed Army Institute of Research, now based in Silver Spring, Maryland. They’d met at a public-health conference a year before. Burke had spent years studying the spread of HIV in the US military, and had noticed that every strain of the disease seemed to point back to the Central African countries of Gabon and Cameroon.

In the late Nineties, Burke made contact with Cameroon’s military, whose public-health officials pointed him towards “bushmeat”, or wild game, taken by rural hunters. When Burke saw Africans hunting wild chimpanzees and then witnessed them surrounded by the blood and viscera of their prey, he quickly made the connection. He deduced that this could, potentially, represent a viral ground zero for humanity. No one had come to this conclusion before. It needed to be researched and Burke asked Wolfe to lead the project.

In 2000, Wolfe moved to Cameroon and began to assemble a remarkable coalition of scientists, bureaucrats, villagers, soldiers and researchers of varying nationalities. Even now, when you ask Wolfe what he does for a living, he says modestly: “My job is to pull together really cool talent.” The project quickly turned into a scientist’s dream assignment. “It’s that perfect balance of being able to wear a suit on the one hand and being out in the jungle on the other, and very often we’re doing both on the same trip,” says Joseph Fair, Wolfe’s chief science officer.

Wolfe became beloved in some of the most remote rural villages on Earth. In Cameroon, they refer to him as grand frère, or big brother. One villager in the Democratic Republic of Congo named her son Docteur Nathan after him. Jeremy Alberga, GVFI’s chief operating officer, says: “They sense the commitment Nathan has towards them.”

But early on, before he had a multi-million-dollar organisation behind him, Wolfe was a lone scientist trying to find the missing link that would prove that viruses frequently jumped from animals to humans. He approached the retrovirology branch of the Centers for Disease Control (CDC) in Atlanta, and, in particular, a scientist named William Switzer. Working together, Wolfe and Switzer investigated something called a simian foamy virus, or SFV, so named because when cells become infected with the virus, they bubble up and die, creating the impression of foam under the microscope.

SFV, as Wolfe explains in The Viral Storm, infects virtually all non-human primates. Each primate has its own particular version of SFV, meaning that if Wolfe and Switzer could find one in humans, they’d be able to tell exactly from which primate it originated. Conventional wisdom a decade ago held that, while cross-species transmission of viruses could happen, it was so rare as to be scientifically irrelevant. But Wolfe suspected that retroviruses flowed regularly from animals into the human population. He went to the CDC to find out.

A shipment of blood samples arrived from Cameroon, accompanied by Wolfe. Within the first few hundred specimens, Wolfe got his first “hit” from the blood of a Central African gorilla hunter. The sample showed that the exact type of SFV carried by the gorilla had jumped into the hunter. It was, Switzer says, “a canary in a cage moment”, the first definitive scientific proof that simian retroviruses could cross directly over into humans.

Subsequent samples showed similar findings. Wolfe, until then an obscure researcher, suddenly had a major scientific discovery under his belt. “We had shown that retroviruses continue to cross over,” Switzer says. “We’re still at risk from these retroviruses, which are capable of creating a pandemic. If we don’t monitor them at the human-primate interface, then we may indeed have another pandemic of retroviruses on our hands.”

The discovery occurred on 11 September 2002. Wolfe has a photo of the slide sample — he calls it the “Western blot” — displayed proudly in his San Francisco office. “It gave us a certain proof of concept that we could monitor the flow of agents into humans,” he says. “I had a slight feeling of foreboding, though. It became instantly clear that it was crazy that new retroviruses were crossing into humans, and not only were existing systems not moving, they weren’t looking in the right places.”

But where other people may have been afraid, Wolfe sensed opportunity. The “Western blot” formed the basis for the amazing work he’d do over the next decade. “That’s when we said, ‘We can do this’,” he says.

In 2008, Wolfe left a rare guaranteed lifetime professorship at the University of California, Los Angeles — the kind that academics murder one another for — to start GVFI. It was, given his academic status and relative youth, an eccentric decision. “I wanted to do something independently,” he says, “and I wanted to do something potentially really big.”

No one doubts Wolfe is up to the challenge. Colleagues describe him as “visionary” and “dynamic”. Given his fields of expertise and the variety of people he’s met working in the field, few scientists could pull off what  he does. “It takes a certain type of person to work in the kinds of atmospheres Nathan does,” says Mark Smolinski, director of global health for the Skoll Global Threats Fund, who, when an executive at Google.org gave Wolfe a multi-million-dollar grant in 2007, commented: “He calls upon a lot of creativity.”

This is an American who managed to pull together military leaders from eight Central African countries into a political alliance designed to monitor and prevent new influenza outbreaks. He did it with  the help of the US Department of Defence, which had funded the construction of Wolfe’s research laboratory in Cameroon. Wolfe brought to bear all the medical diplomacy he’d been developing over the years. “Military-to-military alliances are a niche no one else really cares about,” says Dr Kevin Russell, director of the US Armed Forces Health Surveillance Center at Silver Spring. “Nathan’s not military, but he accepted that challenge.”

“What I do now doesn’t feel that different from what I used to do,” Wolfe says in his unassuming way. “It sort of feels the same. It’s just that I’m doing it in more places.”

Wolfe’s next task is even more far-reaching. He dreams of a day when scientists predict viral outbreaks at the source, which he describes in vivid sci-fi detail in the last chapter of The Viral Storm:

“The large, brightly lit, mostly white-walled room appears at once chaotic and oddly organised. Young kids in their Silicon Valley uniforms of hoodies and sneakers sit hunched over laptops, talking on the phone and instant messaging while simultaneously mashing together and analysing massive amounts of data. Large monitors with maps and streaming news line the walls. There are no windows, so it’s hard to determine if it’s daytime or evening…”

As the scenario unfolds, “an older group wearing suits and formal business attire” — which, we assume, would include Wolfe himself, though his own sartorial style tends towards the casual — arrives to discuss very serious matters. A disease has broken out in Central Africa and the team is crunching data. “Chief medical complaints” are coming in from “an early but robust cell-phone-based electronic medical record system based in Lagos”.

Twitter and Google trends seem to be showing viral outbreaks as well. The team works the phones with various clinics. “The uptick is due to none of the usual suspects,” Wolfe writes. It could be a new disease, and it must be stopped.

“While we’re not there yet,” Wolfe writes, “the control room is exactly what we need — an innovative group devoted entirely to understanding and analysing biological threats and catching them before they become disasters.”

The reality of what Wolfe’s been able to cobble together through various funding sources, while still impressive, is a bit more modest. GVFI occupies a cramped corner of a multi-storey office building overlooking Market Street, the central business corridor of downtown San Francisco. Half the desk space is given over to medical researchers or anthropologists, who are in the field much of the time. Wolfe’s dream team of about a dozen hoodie-wearing Silicon Valley geniuses, many of whom work part-time, is crammed into two tight rows of desks in what used to be GVFI’s reception area.

They’re working on something called Epidemic IQ, which, as the system’s designer told me, is “a cloud-based computer system that will trace outbreaks of pandemics from anywhere in the world”. When I request a viewing, he declines, saying it contains a lot of “proprietary data”. In other words, it’s not ready.

Wolfe’s San Francisco office, though tidy, is just as tight a squeeze as the rest of the GVFI HQ. Every spare inch of wall is covered with names of potential investment or research partners, or phrases you’d never find written on the walls of other people’s offices, like “Weird human malaria”, “Sars seropositive in exposed” and “Unknown pox”. One folder on Wolfe’s desk is labelled “Swine flu origins”; another “Why is cancer?”

The writing extends to one of his office windows. “We ran out of whiteboard space,” he says apologetically. It includes the enigmatic phrase “Monkey sushi”.

In his office, Wolfe talks about the frustrations of trying to realise his ambitions of a comprehensive global disease-prediction network. 

There are resources out there that would allow us to do this in a way that would be systematic across the board,” he says. “The global disease-control budget spent on prevention is decimal dust. We’re not even talking 1 per cent. Let’s just start diversifying the portfolio a little bit. The public’s attention waxes and wanes. The media focuses on the disease du jour. It’s a disastrous way to think.” He hopes to one day get the majority of people thinking his way.

Back at Swan Oyster Depot, he’s long since polished off his bloody beer and goes on to talk about his second-favourite topic.

He was a vegetarian, he says, until age 18, but that time is long past. “One morning, I woke up in Cameroon,” he says. “A guard was in the kitchen chopping up a cobra that had snuck in during the night. I was afraid that would end up being my breakfast. I haven’t eaten cobra yet, but I have eaten python. You’d expect, when you’re eating snake, to have a long thing, but they serve it in steaks. The front end and the back end taste totally different. And it did not taste like chicken.”

He picks up a littleneck clam and tucks into it with delight. “I do my best to receive hospitality wherever it’s offered,” he says.