Stopping the Next Plague
Simon Anthony thumbs his iPhone while standing in line at a busy deli near Columbia University Medical Center in Washington Heights. While waiting to pay for his meatballs and french fries, an e-mail from a radiology lab pinged his inbox: the results from samples of monkey blood serum that he'd had analyzed for an enzyme that betrays the presence of retroviruses similar to HIV.
"Oh, this is interesting," he says without lifting his eyes.
He's searching for zoonotic viruses, the sort that are capable of jumping from animals to humans, which is his specialty. He is a key researcher in the largest-ever virus hunt, a global $75 million project, funded largely by the United States Agency for International Development. Called PREDICT, its aim is to identify "the next HIV" before it breaks out.
In just a couple of years, the 31-year-old has discovered 130 novel viruses. Now, the e-mail on his phone suggests that he will be adding one more.
He is tall and slender, with light brown hair that forms a small wave. In his London accent, he draws out vowels, particularly when he says viiiruses. He is a trained opera singer who practices tap dance and the waltz during otherwise wasted minutes of laboratory life, like waiting for a centrifuge to stop spinning. In and out of the lab, he wears V-neck sweaters, skinny jeans, and stubble, an unassuming uniform for someone who spies on nature's conspiracies to unleash a plague on New York.
Every year, he sifts through 5,000 samples of blood and tissue, many from wild animals in disease hot spots around the world. But he chases down threats close to home, too. Already this year, through molecular detective work, he has uncovered two important finds in New York and the region: specimens related to HIV in bush meat smuggled into John F. Kennedy International Airport and a deadly avian flu that leaped into seals in New England—evidence that it might spread into humans.
Rather than wait for pandemics to occur, scientists like Anthony try to stay one step ahead. This approach, called "biological intelligence," or "surveillance," is similar to how the CIA keeps tabs on foreign governments.
Surveillance is the first step in the modern approach to combating infectious diseases, which have skyrocketed over the past century and kill more people worldwide than cancer. Scientists believe this method is crucial, considering that, like HIV and SARS, three-quarters of new illnesses come from wild creatures.
But Anthony's goal is not simply prediction, but to understand the natural balance of pathogens and what throws it out of whack. Little is known about the universe of viruses, like how and why they hopscotch among species or how many exist. By charting it, Anthony hopes to better understand the dangers they pose, to learn how to prevent transmission, and to create necessary therapeutics.
And his contribution has been remarkable. His discoveries represent about 7 percent of viruses known to science. Although no official count exists, Stephen S. Morse, former director of the Center for Public Health Preparedness, believes the young scientist holds a unique distinction. "I don't think anyone else can make the claim to have found so many new viruses," says Morse, who is the director of PREDICT.
And today, it looks like Anthony is close to another quarry. There is evidence of retroviruses in the monkey serum he had tested. The image on Anthony's iPhone is of X-ray film containing a matrix of dots. Eight of 10 are opaque, a sign that there are traces of an enzyme called reverse transcriptase, a substance retroviruses hijack cells with. He decides to delay other tests, of throat swabs taken from sick gorillas, to pursue the lead. "Maybe I'll just bump everything on my to-do list," he says. "Scientific intrigue trumps everything else."
After lunch, hot on the trail, Anthony hustles to the Center for Infection and Immunity, part of Columbia University, where he is a postdoctoral fellow. The lab occupies the top three floors of a tower on West 168th Street. It has wood floors, glass-walled offices, and large windows framing the George Washington Bridge. Hovering over countertops crammed with tubes and pipettes, more than 60 researchers work at the center. The place hums with the sound of oversize freezers cooling samples—thousands of plastic vials holding the DNA of viruses.
It is one of a half-dozen labs dedicated to pathogen discovery, the science of finding harmful microorganisms, and is one of the best virus-hunting machines on earth: More than 500 novel agents have been discovered there, more than at any other lab. Its scientists have been instrumental in spurring the use of molecular techniques to look for DNA, a widely imitated advancement that allows scientists to find viruses in a matter of days. Until just five years ago, it took years.
Viruses have no cells of their own; they break into a host cell and reproduce, often killing the host. Likened to lunar modules for their shapes, they are one-hundredth the size of bacteria and are not, strictly speaking, alive.
Anthony is searching one serum for retrovirus DNA. He sets up a test called polymerase chain reaction (PCR), a technique used in forensic DNA fingerprinting. PCR copies genes many times, so they are easier to detect. He outfits himself with the weapons of a virus hunter: latex gloves, disposable fabric sleeves, pipettes. And an occasional silly joke: Another researcher who works nearby suggests they write a song describing PCR and post it on YouTube. "It'll go viral," she says. Then, with a look of concentration, he injects monkey serum samples—transparent liquid in clear tubes—into new vials filled with a liquid that will bind to retrovirus DNA.
Many of his discoveries begin this way. His goal is to obtain sequences of virus genetic code, which subsequent steps will fill in. When in hand, Anthony will plug them into BLAST, an open-source database of DNA sequences. If the piece of code is not there, he has discovered another new virus.
The samples—blood, tissue, feces—arrive by mail every three months. Inside a nondescript cardboard box is a layer of dry ice and 500 plastic vials. He inventories each tube and places it into the large freezers, like giant Frigidaires, where they are kept at 80 degrees below zero Celsius. The lab has so many—it receives 10,000 a year for all the projects—some had to be moved to a spillover bank in the Bronx.
Because wild animals produce the majority of infectious agents, the project sends field veterinarians around the world to sample primates, rodents, and bats, which are released unharmed. Those animals are hugely abundant, live near humans, and are close relatives of ours, so viruses they carry can jump to us with relative ease. Most samples are shipped to Anthony.
Periodically, he travels to the Amazon or other hot spots to scope out animal populations for testing. But a sterile lab environment seems a more natural workplace for the London-born scientist, who wears a zebra-striped bow tie. As a colleague from one trip recalls, he was comically "out of his element" in the Peruvian Amazon. Anthony recounts the trip with dry humor. "I'd have my little field gear on, and they'd be like, 'Aren't you hot?'" he says, mimicking his friends. "They took the mickey out of me for wanting to look clean, even when it was sort of sweltering in this blipping forest. I'd be like: 'No. The vest goes with this outfit.'"
His colleague explains, "He wanted to look just right even though we were in a place where there was no looking good."
Although PREDICT was not the first effort to hunt viruses this way, it is the largest. The project is halfway through a five-year grant, and tens of thousands of samples have been collected. Mostly through Anthony's analysis, it has found 150 viruses. "It sounds great; it sounds really impressive," he says. "But it really is just a case of turning over the stones to see what's underneath." The majority of viruses are not harmful; Anthony has not identified anything immediately dangerous. Until he does, the researchers will not begin the costly and time-consuming steps to develop therapeutics. Their discoveries aside, these scientists have hardly left the driveway: By one expert's estimate, the 2,000 known to science represent two-tenths of one percent of all viruses.
The monkey serum (which came from macaques in Asia, though Anthony cannot specify where because of an agreement with a foreign government) has not yet revealed all its secrets. Although the radiological results show the presence of retrovirus's telltale enzyme, he has tested only for known sequences, which were not present. The samples will undergo powerful genetic tests to show the full constellation of what they contain. That preliminary result could actually mean the discovery of a new type. "I'm wondering whether or not we have a divergent retrovirus that is different enough that it is not being picked up," he says.
The same animals Anthony surveils in distant jungles are smuggled into New York's airports. In fact, to obtain some of his most important samples, he and his colleagues only needed to drive to Queens. When authorities at Kennedy International Airport seize illegal bush meat, they call the scientists to sample it before incineration. In 2010, he and his colleagues began to study bush meat confiscated at Kennedy and airports in Washington, Philadelphia, Houston, and Atlanta.
Bush meat is eaten around the world for subsistence and tradition. In some African cultures, the meat is believed to posses spiritual qualities and impart strength and courage. In parts of central and west Africa, bush meat accounts for as much as four-fifths of dietary protein. Unlike in Asia and South America, where primates are rarely consumed, in equatorial Africa, nonhuman primates are more common fare.
The most abundant types of bush meat are exactly what PREDICT is looking at: primates, rodents, and bats; and handling meat is an effective way of contracting viruses they carry. More to the point, it is widely accepted that HIV leaped to humans through the hunting, butchering, or consumption of chimpanzees in west Africa. Likewise, SARS was transmitted from civets, a wildcat prized as a delicacy in China.
According to records obtained by the Voice, authorities at Kennedy airport have seized 130 pounds of bush meat in the past five years. Items labeled as "NHP"—nonhuman primate—were among the things port officials could identify.
During that time, officials at Dulles International Airport seized 236 pounds of "smoked monkeys," "bats cooked whole for consumption," and rodents. More than 1,000 pounds were intercepted at the Elizabeth, New Jersey, seaport, along with smaller shipments at Connecticut's Bradley International Airport. Records show most shipments originate in a few countries: Nigeria, Ghana, and Cameroon among them.
We can only guess what authorities do not find, but one estimate holds that 15,000 pounds of bush meat slip through U.S. customs every month. "I feel there is a lot of stuff that gets through that we don't see at the moment," Anthony says. Globally, the trade is far bigger. One study found that nearly 300 tons of bush meat entered Paris's Charles de Gaulle airport annually.
The scientists analyzed bone marrow and trachea from green monkeys, spinal nerve and eye from baboon, and flesh from mangabey and chimpanzee, all primates. Photographs of the meat show two intact monkey heads, one with the torso still attached, a furry, curled hand and a complete eight-inch arm. In January, the scientists published their findings in the journal PLOS ONE. They announced that the primate meat contained two strains of herpes and four of a species called Simian Foamy Virus. SFV is related to HIV and known to infect humans, but it has not been linked with disease. Still, the presence of these viruses "highlights a potential health risk," they wrote.
Much bush meat is dried or smoked, which can effectively kill pathogens. But deep below top layers kissed by smoke or sun, viruses survive in moisture-rich places like uncooked tissue, bone marrow, eyeballs, and brains. "If you're importing a piece of jerky, I don't think the level of risk is very high," Anthony says. But government photographs of bloody meat in plastic bags show different. Of the chunks examined in the study, the scientists wrote, "most items contained moist inner tissue."
Today, scientists comb the natural world first and later ask if a species they find is pathogenic. For most of modern history, they saw fit only to study agents known to cause disease.
In 1951, Manhattan's Rockefeller University took an early step in that direction, establishing searches, as one historian writes, "aimed in a shotgun approach at 'what may be out there.'" A string of discoveries followed, but within two decades, money ran low, and it abandoned the project. By the 1980s, still a fringe pursuit, pathogen discovery had all but fallen away.
But in the 1990s, techniques from molecular biology were first applied, and the field underwent a renaissance. Suddenly, after decades of slow and faulty methods—growing viruses in lab rats or petri dishes—scientists could detect them with simple tests.
W. Ian Lipkin, director of Anthony's lab at Columbia, was the first person to do this. In 1990, he pioneered this practice by identifying that a virus causes a neurological illness in horses, a process that took three years. In 1999, he discovered that West Nile virus caused the outbreak of deadly encephalitis afflicting New Yorkers. He was invited to be the lab's director in 2002. At the time, it was "a couple of empty floors that needed to be renovated," according to Morse, his colleague then and now. Last year, he acted as scientific adviser on the bio-thriller Contagion. Today, he is investigating whether viruses are behind the unknown causes of chronic fatigue syndrome and autism.
Lipkin built the lab around pathogen discovery, all the while developing new techniques. He and his colleagues invented a new diagnostic method for identifying microbes, MassTag PCR, that instead of detecting single microbes, detects dozens of bacteria and viruses at the same time. He helped develop GreeneChip, a glass slide containing 500,000 genes that is used to test for virtually all known pathogens. His methods were fast and cheap. As he led the charge, the time needed to find a virus shrank from years to days. A team of scientists at his lab can identify an unknown pathogen in hours.
As the field matured, outbreaks were fueled by globalization. A major study published in Nature in 2008 showed an increase of outbreaks in each of the past six decades, nearly quadrupling between the 1940s and the 1990s, when there were almost 100. Infectious diseases are now the second-biggest cause of death worldwide, after heart disease. They account for 17 million deaths per year and kill one in six in developed countries and twice as many in the developing world.
The increasing menace made scientists "sit up and take note," as Anthony puts it. They would soon pick up where the "shotgun approach" left off, but they did not know where to search. A colleague of Anthony's, Peter Daszak, had an idea. In 2008, he published an influential study mapping the places where diseases are most likely to emerge, based on geography and past outbreaks. These "hot spots" are the Amazon and Congo basins and the most densely populated parts of Europe, China, India, and North America. Basically, any place humans and animals are crammed together. New York, the archetypal dense global city, is a bona fide hot spot.
The new model "changed the way people looked at [outbreaks]," Anthony says. It gave rise to "the very concept that this may not be so random." The year after the map was published, literally using it as a guide, several organizations embarked on the global hunt.
As the field's renaissance unfolded, Anthony, the son of a onetime pub owner and an opera singer, graduated from the University of Wales, where he studied zoology. He was offered a job as an elephant keeper at the London Zoo. But the next day, a keeper tripped and was killed when an Asian elephant stepped on him. Because of that, Anthony decided not to go.
At the time, foot-and-mouth disease was at its height, leading to the deaths of millions of cattle in Great Britain. Enjoying lab tests to find evidence of viruses, he joined the effort to study it. Later, he earned a doctorate in molecular virology at Oxford, where he began using time in the lab to tap dance and waltz—remnants of his days as a young operatic baritone. He took a fellowship at the San Diego Zoo to focus on wildlife disease before being hired by Columbia. Although he works closely with Lipkin, Anthony has free rein to do what he pleases. "I'm working on the next level of pathogen discovery," the young scientist says.
Their shotgun approach to finding viruses has its share of deep-pocketed supporters as well as critics, who point to the failure to head off a public health catastrophe, much less find "the next HIV."
"What have they found? Not much," says Robert B. Tesh, a respected senior virologist at the University of Texas Medical Branch who is not involved in PREDICT. "In my opinion, it's a lot of hype."
Anthony didn't bristle at that swipe by a fellow scientist. Although the aim is to prevent the next great pandemic, he points out that there's a lot of less dramatic groundwork that has to come first.
"Our aim is to gather information about the different viruses that exist in wildlife, and this is no small challenge," he says. "We are at the beginning of a long road here."
He adds: "This project is not designed to avert global pandemics in two years, or even five years. This is a long-term initiative, and over that long term, we will gather much more information about viruses that exist and implement the ability for countries all over the world to respond as they occur. The goal was never to do it within two years, because that's impossible."
Anthony adds that while critics exist, PREDICT has garnered partnerships from major research institutions, Columbia and University of California, Davis, among them, as well as 20 nations that have signed on. PREDICT scientists help labs in those countries improve pathogen discovery, at times building labs from the ground up. "That's a huge contribution to public health," he says.
"The other thing you have to bear in mind is how do you measure whether we've averted a health crisis? We have the unfortunate situation where if we are successful in setting out to do what we want to do, we'll never know it. . . . But we can measure the number of viruses we have found, our knowledge of global viral diversity, and the labs we've set up around the world."
Anthony walks to one of the lab's massive freezers to retrieve some gorilla throat swabs, the samples he'd put off to look at monkey serum. He pulls the door open, and mist pours out. Inside, dozens of shoebox-size containers hold tubes scribbled with letters.
He dons an insulated glove, brushes frost from a box, and slides it out. The swabs, like mini Q-tips, were taken from Rwanda gorillas that might have contracted something from humans; the virus travel works both ways. (This happened in 2009 when gorillas in a Rwandan national park died of a human respiratory infection, theorized to have jumped from ecotourists.)
Anthony wants to know what viruses are on the swabs, both gorilla and human. But because the samples have not yet been lysed—a process that renders pathogens incapable of infecting—there is a chance he could inhale a virus. The job must be done in "the BL3," as he calls it, a special lab named for its next-to-highest biosafety level.
Behind a door marked "Biohazard," he pulls a protective suit over his skinny jeans and slides a respirator over his hair. Looking like an extra in a Contagion sequel, he extracts liquid from the vials holding the swabs. Then he spins it in a centrifuge to separate bacteria and gorilla cells, which form dense pellets.
With a needle, he removes the liquid while making sure not to suck up the pellets. Next, he injects it into yet another vial, this time inserting a fine filter with holes large enough for virus particles, but not cells. Again, he spins the tubes in a centrifuge to push the liquid through the filter, hopefully leaving a "fairly pure" sample: a few drops containing only viral DNA.
Standing by the centrifuge, there is nothing to do but wait. Moments like that are when he waltzed while earning his doctorate. And he might do a few steps in the BL3, too, but it is nearing the end of a long day, during which he has zipped up the stairs between the lab's floors many times. His stubbly face looks weary through the helmet, slightly crooked on his head. Inside the respirator mask, a tiny lightbulb (indicating that the electric filter is on) gives his face a blue cast. When he speaks, his voice sounds like he's talking into a bucket. "I spend half my life writing on tubes and waiting by centrifuges," he says.
Later, he would find that the throat swabs held a bounty of viruses: an adenovirus, a form of which can cause pneumonia in people; a new enterovirus, related to the human kind, a type of which causes polio; and five kinds of polyomaviruses, at least three of which are brand new.
And as is often the case, he found mysterious genetic sequences—"dark matter"—that don't fit with any known life-form. About a third of the genetic codes he finds are dark matter, unidentifiable shadows at the edge of scientific knowledge. "It may be rubbish; it may be bacteria," he says. "It could be anything."
On a recent afternoon, Anthony sits at a small table in the atrium at Lincoln Center. On weekends, he makes the 100-block trek from his apartment, by the lab, to work here. The former baritone likes being near the Metropolitan Opera, which he attends when he can. With his coffee and laptop, he could be any New Yorker or English tourist. Instead, he is a guy whose job is to know what conspiracy nature has in the works. And he might be the first person to know when it has been unleashed.
He explains his most recent bit of spying on the natural world. It began last fall when dead harbor seal pups began washing ashore in Massachusetts, New Hampshire, and Maine. Over four months, 160 seals, many of them juveniles, inexplicably died. Surfers bumped into their bloated carcasses, which tossed among the waves and littered foggy beaches. The animals had not expired due to injury or malnutrition, common causes in the wild. They had succumbed to severe pneumonia brought on by a respiratory infection that left lesions on their trunks and flippers.
Local authorities sent Anthony lung tissue from five infected seals, and the detective set to work. He tested for a wide range of pathogens and within two days had found a suspect: an unknown influenza subtype. By the end of the week, he had compared its genome to that of other viruses, and found that it is closely related to a flu that infects the intestinal tract of ducks. Somehow the virus jumped hosts, probably along the shore where the animals' habitats overlap.
The resulting paper was published in the journal mBio in July. A couple of months earlier, the U.S. government had asked scientists to withhold research about dangerous mutations in bird flu because of security reasons. Major news organizations picked up the study (as did the The Onion, which ran a fake man-on-the-street interview series: "Aw, jeez, now you tell me. I just picked up a couple of seal steaks at the Price Chopper," lamented Barbara Suarez).
Anthony explained the subtle threat to the world. To invade cells, viruses use receptors, like little doors. This virus, now known as seal H3N8, had acquired a key to seal cells, when before it had only keys to bird cells. After jumping into seals, it adapted to jump between them. "Because of that, there's every likelihood that this virus can therefore infect other mammals, too," he says. Without further study, no one knows whether seal H3N8 might leap to people, much less if it could be as deadly as H1N1, a flu strain that killed 10,000 people in six months during 2009.
The jump to mammals from birds is bigger than a jump between two mammal species. In other words, the virus had already made the difficult initial leap. Anthony can't be certain seal H3N8 is capable of infecting humans, but it has a stronger chance now that it has migrated to one mammal. "You have to imagine the possibility is certainly there," he says.
At times, the reaction to his discoveries and those of others can be overblown, he says, citing undue fear that we are "one or two mutations away from a pandemic." If that were true, "there would be outbreaks every other day, and as a species we would have a hard time existing," he says. Until science has mapped the universe of pathogens, no one can say precisely what reaction is appropriate. We know only that every landing airplane, every infected seal, poses some risk. "I think it is also important to emphasize that it is very unlikely that seal flu will either jump into people or cause disease simply because these events are so rare," he says. "What is important about this study is that it teaches us about how viruses emerge in new mammalian hosts."
On this rainy day, he shares a table with an aging woman in the packed atrium. She eavesdrops as he speaks about how pathogen discovery is done and the need for scientists to continue the shotgun approach. As she stands up to leave, she mentions her amazement at how far science has come. It was the second time in weeks that a stranger in the atrium said something like that. He has gotten such comments many times.
Just the other day, he was opening a bank account at a Chase on Ninth Avenue in midtown. The banker offhandedly asked, "What do you do?" When he told her, she wrote her phone number on a piece of paper, handed it to him, and said: "Give me a call when you find something serious. I want to be the first to know."
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