“Fire!” A baritone retort accompanies a spray of tawny sand as a large cannon net stretches wide. Small shorebirds with white bellies and mottled orange and black feathers try to flee, but the net is faster: It settles and traps a flock of Ruddy Turnstones underneath. A ragtag crew leaps up and dashes to the indignant birds. With an efficiency and precision that Henry Ford would have envied, the team gets to work.
Migratory birds pack the New Jersey Shore for the same all-you-can-eat seafood buffets and fresh ocean breezes that attract humans. Only their journey is far more epic. Every year, tens of thousands of Red Knots and Ruddy Turnstones winter as far away as Tierra del Fuego, off the southern tip of South America, and travel hundreds or thousands of miles to Delaware Bay. Dunlins, Semipalmated Sandpipers, Sanderlings, Herring Gulls, and Laughing Gulls join them there. As humans feast on popcorn shrimp and fried clams, the birds pursue horseshoe crab eggs with a single-minded obsession. The bay’s bountiful supply can double the weight of Red Knots—stripped of their energy by a week or more of flight—in just a few weeks.
Shorebirds, however, pick up more than fat reserves during their stay. The mingling of so many birds, packed beak to tail, along small stretches of sand creates the perfect breeding ground for disease. When they arrive from their winter habitat to Delaware Bay, only low percentages of turnstones, for example, have antibodies to influenza. By the time they restart their journey to Arctic breeding grounds, tests can show roughly 60 percent have been exposed.
All human influenza pandemics begin with a strain of virus that evolved in wild bird populations. The virus doesn’t appear to harm the wild birds, but it can occasionally spread to other animals and jump to people. When that happens, the outcome can be mild—or devastating. In 1918 influenza created the deadliest outbreak in recent history, killing upward of 50 million people (2 out of every 100 human beings alive at the time).
That’s why a team of scientists gathered on the Jersey Shore’s Delaware Bay last year, as they have every May for nearly four decades, netting hungry shorebirds to swab them for viruses. “It’s very important to know what these viruses and their genes are doing out in nature,” says David Morens, the senior scientific advisor at the U.S. National Institute of Allergy and Infectious Disease, who has spent his career studying influenza and other emerging viruses.
The spring of 2020 was different. Because of measures enacted to slow the spread of the coronavirus pandemic, the boardwalks were empty of tourists, the seafood buffets shuttered, and much of the team that usually monitors avian flu remained in Tennessee and Georgia. COVID-19, meanwhile, was showing the world yet again how a novel virus can tear through every country on Earth, leaving hospitals overwhelmed, morgues overflowing, and economies in shambles. Unfortunately, one pandemic doesn’t leave us immune to another. For decades, some experts have predicted that humanity is long overdue for a repeat of the devastating influenza crisis a century ago. It still is, and humans aren’t helping their chances.
Hippocrates and other ancient Greeks described a disease that was almost certainly influenza, characterized by high fever, body aches, fatigue, malaise, and a cough, all with a sudden onset. As centuries passed, physicians noticed that influenza showed a distinct pattern. Although the disease returned every winter without fail, most years the toll was relatively mild. Every generation or so, however, a raging inferno of influenza would burn through the population, killing not only the weak and vulnerable but also the strong and vigorous.
Transported around the globe by soldiers fighting in World War I’s muddy trenches, the 1918 virus’s toll eclipsed the carnage from bullets, grenades, and mustard gas. Otherwise healthy young adults could be fine on Monday and dead by Sunday. What made the plague more terrifying was how little scientists knew about the entity that caused it. In its wake, scientists established the movement of flu viruses between chicken, swine, and humans, but no one knew influenza’s reservoir—the animal in which it survived, circulated, and evolved between outbreaks. After another, less devastating flu pandemic in 1957, which began its circumnavigation of the globe from China, the decade-old World Health Organization encouraged investigators to hunt down the unknown host.
In the mid-1960s, Robert Webster, then a young graduate student at the Australian National University, was walking along a New South Wales beach with colleague Graeme Laver. Every few yards, the men had to sidestep the gray-feathered corpse of a Wedge-tailed Shearwater. Webster recalled a 1961 outbreak of avian flu that killed terns in South Africa and wondered if the same flu could also be found in living shearwaters. He and Laver sailed to sandy cays off the coast to find out. The pair spent days snorkeling and nights capturing every bird they could find, prying open beaks, and swabbing. When they analyzed their results, they were surprised to find that one of the shearwaters had antibodies to the 1957 pandemic virus that had spread in humans a decade earlier.
They also soon realized that the avian flu deaths in South Africa had been relatively rare. Waterfowl and shorebirds could be infected by flu, but they almost never showed any symptoms. The findings, combined with key follow-up studies, suggested to scientists that migrating birds not only were the missing long-term influenza hosts but were also akin to asymptomatic super spreaders of the novel coronavirus today. “These birds are able to have a virus, move the virus, but not become too sick from it,” says University of Georgia wildlife researcher Rebecca Poulson.
In other words, scientists had answered the question of where new flu strains came from, and they also revealed the virus’s winning evolutionary strategy: a host that could make trillions of copies of its genome, seed its genes around the world, and mix them to create novel, potentially lethal, strains with each passing year.
Viruses are small and, at face value, powerless. They don’t even have the minimal genes required to sustain basic life functions. Instead, they rely on their hosts for everything but the 10 genes they bring with them. In most viruses, these genes sit on a single piece of DNA or RNA. Influenza, however, has divided its genome into eight pieces of RNA. If two different flu genomes mix in the same cellular soup, the RNA segments can shuffle around. This reassortment can cause new strains of influenza to emerge out of the blue and with deadly effect.
The two most important genes that help scientists track new flu strains code for the proteins hemagglutinin and neuraminidase. Abbreviated H and N, they help the virus bind to cells in the respiratory tract and bud off from the host cell after replicating, respectively. They also form the two major ways the immune system recognizes an influenza virus to stimulate antibodies. Scientists have identified 16 different Hs and 9 different Ns in bird species around the world, for a total of nearly 150 possible strains.
For a bird influenza virus to directly infect people, “it’s sort of like putting a round peg into a square hole,” says Poulson. The cells lining the human respiratory tract look very different to the virus. That’s in part why only five of these strains have ever caused disease in humans. Two (H1N1 and H3N2) are currently circulating as normal “seasonal” influenza and are the reason we get flu shots. Another (H2N2) has circulated in the past. Two other strains (H5N1 and H7N9) have caused only small, localized outbreaks.
To cause a pandemic, however, a virus needs to do more than just infect humans. It also needs to spread from person to person with ease and be different enough from other recently circulating flu viruses that few people have immunity. Each strain has many genetic variants with slightly different properties that affect how infectious and deadly they are and also determine our immune response. By keeping an eye on the different strains circulating in wild birds, Webster reasoned, scientists might be able to identify a potentially dangerous virus.
“The more we can understand about the true diversity of viruses, we get a better idea of what the future diversity of pandemics could look like.”
Webster decided to investigate this theory after moving to the United States for a job at St. Jude Children’s Research Hospital in Memphis. In 1985, along with collaborators from the University of Georgia, he won a grant and hired virologist Richard Webby to establish a long-term sampling project at the annual avian gathering in Delaware Bay. The team has since returned there after every first full moon in May, when the crabs come ashore to lay eggs, to swab and band migratory bird species.
Around the world, more than 119 countries now sample wild birds for influenza. But today, Delaware Bay is one of the only places where scientists conduct active surveillance, making the effort to look for viruses in live animals rather than merely responding to reports of dead birds. The result, says Andrew Ramey, a wildlife geneticist at the USGS Alaska Science Center in Anchorage, is a rare, long-term view of the never-ending flux of influenza strains in reservoir species.
“The more we can understand about the true diversity of viruses, we get a better idea of what the future diversity of pandemics could look like,” says Webby, who still helps run the sampling project with St. Jude researcher Pamela McKenzie.
Annual trips to Delaware Bay by the team began to offer a snapshot of the virus in the wild. An analysis of early data from this research, along with samples from across North America and Eurasia, showed that domestic poultry were typically infected with influenza from nearby shorebirds and waterfowl. But the regular appearance of unknown flu viruses in poultry also showed virologists that they have barely scratched the surface in understanding influenza diversity, which made it all too likely that a new variety would strike chickens—and perhaps humans—in the near future. Webster began warning of this in the 1990s. Within the decade, these warnings would come to life.
In May 1997 a 3-year-old boy died at a Hong Kong hospital from influenza, which almost never kills healthy toddlers. But the virus responsible wasn’t the ordinary seasonal flu circulating at the time. It was an H5N1 virus, one that had only ever infected birds, not humans. Webster and Webby immediately feared that it could spread across the globe.
For six months, nothing happened. Starting in November, however, 18 more cases appeared in Hong Kong. Six people died. The human virus was more than 99 percent identical to one that had killed chickens. Scarier still, it had jumped directly from chickens to humans without a pig intermediary, echoing what some experts believe was the arc of the catastrophic 1918 pandemic. To the world’s relief, however, this H5N1 did not readily spread from person to person, which kept the Hong Kong outbreak in check.
The outbreak’s epicenter was Hong Kong’s live-bird markets, which keep all variety of birds in small cages to be slaughtered and processed for fresh meat for customers. Twenty percent of the chickens there tested positive for the virus. The Chinese government responded by culling all 1.5 million birds in Hong Kong’s wet markets. However, Webby and other experts knew that the true source lay somewhere in the billions of migratory birds that soared across the skies of southeast Asia. With such an impossibly large reservoir, this H5N1 would inevitably bubble up again in places where humans and chickens lived cheek by jowl.
In his work in wet markets around the world, including in cities such as Cairo, Egypt, and Dhaka, Bangladesh, Middle East–based virologist Ghazi Kayali sees scenes similar to Hong Kong’s live-bird markets. Cages of wild and domestic birds stacked to the rafters. Minimal cleaning. Droppings everywhere. The stress of captivity causes increased viral replication in birds, which means more virus in those droppings. A novel pathogen—and not just flu—couldn’t ask for a better environment to make the jump to humans, Kayali says. (The COVID-19 coronavirus, too, was first associated with a wet market in Wuhan, China, though its origin source is not definitive.)
Wet markets aren’t the only problem. In developing countries where wages are rising, human appetite for chicken is increasing rapidly. Although industrial farms have control measures to prevent the introduction of a virus, they can still pose some risks for spreading infection. Growing numbers of large informal farms are more dangerous, says Eric Osoro, a medical epidemiologist in Nairobi, Kenya. Whereas backyard chicken farmers once raised a dozen or two birds for their family’s use, now these farms can house hundreds or sometimes thousands of chickens, often in cramped quarters near human living space. “We are growing birds everywhere, and they are defecating viruses,” Osoro says.
The constant shuffling of influenza genes continues.
As a result, public and animal health officials must always be on the lookout for new outbreaks, whether from chickens, domestic ducks, or other intermediate species. Sometimes, as with the 2009 “swine flu” pandemic, the go-between is pigs. In 2013 a leap happened again, with an H7N9 avian virus that first emerged in southern China; like H5N1, the disease had a high mortality rate but was not easily transmitted between people.
Although many new avian flu strains have appeared first in Asia, they don’t stay there. In total, more than 60 species of waterfowl and shorebirds—including ducks, plovers, godwits, tattlers, and Dunlins—migrate from Asia to Alaskan breeding grounds. There they mingle with birds that migrate in the Americas. These intersecting flyways allow birds from North America to pick up flu strains from far-flung regions and carry them onward, says Ramey. This is exactly what happened in November 2014 when poultry farms in British Columbia’s Fraser Valley reported outbreaks of highly pathogenic avian influenza. The H5N2 virus never caused cases in humans (although some farm workers developed antibodies), but it still led to more than $3 billion in agricultural losses before it was controlled. Government officials reported the H5 came from an H5N1 avian flu virus in Asia, but the N2 was from North America. Somewhere in between, Ramey says, the flu viruses must have shuffled genes.
The constant shuffling of influenza genes continues. In June 2020, amid the COVID-19 pandemic, Chinese scientists released an analysis of flu viruses found in nasal swabs from more than 30,000 pigs over seven years. They showed that a worrying new variety of H1N1 virus was growing more common. The novel virus contained a mixture of three different flu viruses: a strain previously found only in wild birds, the H1N1 strain from the 2009 flu pandemic, and a North American H1N1 flu virus (itself a mixture of other strains).
The makings of still other lethal human viruses exist in wild bird reservoirs, but the challenge—and hope—is that they can be identified early. These studies could help scientists be more prepared if and when a new deadly mix breaks out from birds and circles the globe, says Morens of the U.S. National Institute of Allergy and Infectious Disease. “If we can identify it early on when it happens,” he says, “we can try to control it or have a vaccine.”
The world has changed dramatically in the decades since the St. Jude crew began its annual expedition to Delaware Bay. Humans have converted millions of acres of rainforest in South America and Southeast Asia to farms and ranchland. Carbon-dioxide levels in the atmosphere have continued an exponential rise, from 346 to 414 parts per million. Once predictable patterns of bird migration have become syncopated as climate change alters global temperature and precipitation patterns, affecting when and where populations of birds mix, especially in the Arctic, where so many wild birds breed.
In the past decade, epidemiologists have warned that climate change will shift and, in some cases, increase infectious-disease risks. That includes mosquito-borne diseases like malaria and chikungunya, as well as bacteria and viruses like dengue, hantavirus, Lyme disease, and plague. The constant flux of strains in Delaware Bay has, so far, made it tough to identify a current climate change effect in the avian flu data, says Webby. Nevertheless, he expects that future climate shifts that affect wild birds will also change how their viruses mix, both at popular pit stops like the Jersey Shore and at the poles of the Earth. A 2012 mathematical model, for example, predicted that climate change could alter the arrival time of Ruddy Turnstones in Delaware Bay, increasing the chances that they are infected with influenza viruses from resident Mallards and American Black Ducks.
It’s one of the big what-if questions that keep virologists like him up at night
Even more worrisome, Morens says, are increasing encounters between humans, livestock, and wildlife. Wet markets are receiving attention now, due to the coronavirus pandemic, but Osoro cautions that another danger for breeding new pandemics is humans turning forests, marshes, and other healthy ecosystems into agricultural land. Birds, bats, and other wildlife that once remained miles from humans are now living in their backyards, right alongside intermediate hosts that make it easier for deadly viruses to spread. More than two-thirds of newly recognized pathogens that now threaten humans come from wildlife, including the novel coronavirus that causes COVID-19. And with an estimated 1.5 million unknown viruses in mammals and birds, some will almost certainly be able to infect humans.
The current coronavirus pandemic has underscored the importance of surveillance for influenza and other pathogens circulating in wildlife, Webby says. It’s one of the big what-if questions that keep virologists like him up at night: If the world had known about the existence of this novel coronavirus several months before the first cases emerged, could the pandemic have been foreseen, if not averted? But governments have been reluctant to pay for such work, Webby cautions.
Scientists learned after the 2002 SARS outbreak that it was far from the only coronavirus circulating in bats. After MERS in 2012, virologists warned the world that another deadly coronavirus spillover in humans wasn’t just possible, it was probable. Webby and Morens hope that COVID-19 will encourage more public investment in wild-animal disease surveillance systems and cause people to pay more heed. But it remains to be seen whether any lessons from this pandemic will stick.
At least the Delaware Bay sampling work moved forward this year. Instead of the usual team of 50 scientists and volunteers, only a small handful of people, all bedecked in masks, gathered on the sands of a New Jersey beach in the breezy May pre-dawn.
Adding to the strangeness, rather than arriving to sands covered with a muted kaleidoscope of famished Red Knots and Ruddy Turnstones, the reduced human team found beaches with far fewer birds. Horseshoe crabs laid their eggs late this year because the water was cooler than usual, and birds seemed to have decamped for more nourishing feeding grounds before gaining the necessary weight to succeed in the Arctic. Although this year’s timing mismatch between shorebirds and crabs is not necessarily linked to a changing climate, the experience could be a harbinger of future disruption within birds’ ranges if crucial natural cycles fall out of sync.
As it has for 35 years, the sampling proceeded. A team weighed, measured, and banded several shorebird species. Researchers swabbed cloacas and gathered pea-size clumps of fresh feces. “Food goes in one end, but there’s plenty of stuff going out the other as well,” Webby says with a laugh. Suspended in that “stuff” are potentially millions of influenza viruses.
By sequencing the viruses in hundreds of such samples, Webby and his team hope to glean what makes one spread well among birds. They can also pull out signals that a particular virus might adapt to humans and identify, at the genetic level, what gives it the ability to readily move between people. Virologists have yet to complete analysis of the 700 or so samples collected this May. Webby doesn’t anticipate that he will find signs of the Next Great Influenza Pandemic in his plastic tubes of poo. But the possibility that there might be some such sign is what keeps scientists watching the birds on Delaware Bay year after year.
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