CAPE MAY BEACH, New Jersey – For 360 million years, this patch of New Jersey shoreline — and dozens of other spots along the Delaware Bay — has been a crucial mating ground for horseshoe crabs. Every year during the first full moon in May, tens of thousands of them come ashore to bury their eggs in the sand.
But more important to molecular virologists like Lisa Kercher are the swarms of migratory birds that follow.
Red knots from Argentina, with their charcoal bills and plump, rouged stomachs sticking out. Fast-swooping ruddy turnstones dive bomb the beach, careening into a landing on stocky orange legs. Up to 25 species of shorebirds participate in this crab egg buffet. And they all give “flu hunters” like Kercher important clues about avian influenza, and how to prevent the next major pandemic.
Bird flu, as you’ve probably heard about it, can be a troublemaker when new strains cross over into humans. From 1918 to 1919, when a version of avian influenza known as the “Spanish flu” developed the ability to infect people, it spread to one of every three people on the planet and ultimately killed 30 to 50 million. Today, that would be as if the entire populations of Canada or Spain died during the course of two years.
Highly pathogenic versions of influenza, like the 1918 plague, are created when two or more flu strains have the opportunity to infect the same cell — such as when a bunch of migratory fowl hang out with local birds on Delaware Bay. When two viruses meet and swap genes in the cell of an unlucky bird, the odds increase that a monster will be born.
“When [the birds] are here, they are in such high concentration that a lot of mixing goes on with the viruses that they’re carrying,” said Kercher, who works with St. Jude Children’s Research Hospital in Memphis, Tennessee, as she stood near a pack of red knots compulsively pecking at the sand.
Kercher is continuing a St. Jude’s tradition that has sent a team to the Delaware Bay every summer for 34 years to monitor the evolution of influenza strains in these wild birds. Every time they have conducted one of these ecological surveys they have found a strain of avian influenza in at least one fowl. By keeping tabs on what’s in the wild, the team can better prepare us for the next pandemic.
“There is no other place — that we know of — that carries this much influenza in these birds,” Kercher said.
But Kercher and company are not the only “flu hunters.” Across the country, scientists are relying on animals to prepare the nation’s defenses against future pandemics. These researchers flock to state fairs searching for pig-specific flu viruses that cross over into humans. Others raise chicken eggs — millions of them — or insects to support America’s stockpile of flu vaccines, both old and new.
“You are not fighting yesterday’s battle,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. “Even though we are much much better off now than we were back in 1918, we are still not optimally prepared.”
Hunting for bird poop
Cape May cordons off huge swaths of its beach when the horseshoe crabs arrive. The crab population had been dipping for years, due to overfishing and the practice of harvesting their blood for biomedicine, so their breeding grounds are considered precious.
But the St. Jude’s team has a special permit to duck under the cordon tape and look for the key to surveilling avian influenza: bird poop.
After wading through a seaside rivulet, Kercher and four other flu hunters stopped on a knob of beach covered in guano (yes, poop). Stooping over, sometimes on hands and knees, St. Jude’s all-women team swabbed the white droppings with Q-tips, before dropping each sample into a labelled tube. Those tubes get carefully placed into a rollaway beverage cooler — as if packing for a tailgate party but for biological analysis.
“Genetic markers in the poop identify which species of bird the guano came from,” said Kim Edwards, who was trying her hand at fieldwork after serving for 10 years as the lab’s data manager.
Today, the project is focused on guano from red knots and ruddy turnstones, which make a pitstop at Cape May on their way to summer breeding grounds in the Arctic. Both travel huge distances to reach the Delaware Bay — the red knots from Tierra Del Fuego, Argentina, the bottommost point in South America, and the ruddy turnstones from the southern United States.
Both can make their journeys without stopping, which is a great way to lose weight. During their weeklong feast on horseshoe crab eggs, the red knots must consume their full body weight — five grams — every single day in order to refuel for the trip to the Arctic.
The poop, as well as swabs of bird beaks, can reveal which flu viruses are mingling at this pop-up aviary.
Researchers drive all of the specimens down to their lab in Tennessee, where they comb over the viral genes — keeping an eye out for shorebirds that are found to carry multiple strains of influenza at once. Last year, one of the shorebirds they encountered had four types of flu pumping through its body.
Most of the viruses on that beach are considered “low-pathogenic” — or not harmful to the birds themselves, people and wildlife, said Alinde Fojtik, a wildlife biologist at the Southeastern Cooperative Wildlife Disease Study, which collaborates with the St. Jude’s group.
But if a couple of those viruses cross paths and swap the wrong combination of genetic traits, it can produce a “high-pathogenic” strain, like Spanish flu or H5N1, which ran amok worldwide in 2004.
Highly pathogenic strains pose not only a threat to humans but can wipe out whole farms of domestic animals, like chickens and pigs.
“You can get flu from pigs, and a lot of the pandemic flu viruses have a lot of swine sequences in them,” Kercher said.
A hog wild hunt for swine flu
Pigs are potent breeding grounds for influenza — known as viral reservoirs — because their cells are readily infected by flu viruses that typically live in other animals. Scan the genomes of some of the worst pandemic flu viruses — like H1N1 — and you’ll see signs that the virus spent time in swine.
“If we talk about the H1N1 virus that we have circulating in people today, that came out pigs in 2009,” Andrew Bowman, a veterinarian who specializes in preventive medicine, told the PBS NewsHour inside a county fair in northern Ohio.
Bowman serves on a surveillance team that wants to prevent new versions of the swine flu from spreading to the 150 million people who attend agricultural fairs in North America each year. To do so, he heads to county fairs where he swabs the noses of the pigs on display.
If a pig is infected with influenza, “they’re going to have a nasal discharge. They’re going to have a cough, runny nose, those sorts of things,” Bowman said. “If you get enough animals shedding virus simultaneously, and creating a high-enough viral burden, you could certainly have airborne transmission into a person.”
Pigs act as a bridge. They can be infected by bird flu varieties that you don’t typically see in humans.
“If a virus is able to replicate in a new host and able to transmit human-to-human, then it’s going to take advantage,” Bowman said. If bird germs mix with the right partner inside of a pig, then a strain can emerge that our bodies aren’t prepared to fight.
That’s why the H1N1 pandemic in 2009 spread so fast, with 60 million cases in the U.S. alone. It caused 270,000 hospitalizations and 12,400 deaths in the first year of the outbreak, especially among young people.
Humans hadn’t dealt with a H1N1 virus of this stripe since the 1918 outbreak, meaning older people had some immunity, but everyone else was vulnerable. Four out of five of those deaths involved people under 65, the opposite of what’s typically seen with seasonal flu.
These swine pandemics don’t mean you need to skip your state fair, but it raises the need for active surveillance.
“If we talk about 150 million people attending fairs, worst case is a couple hundred cases of flu in a given year,” Bowman said. “But realize, any one of those could be the one that starts the next pandemic.”
Which came first: the vaccine or the egg?
Once a flu hunter — whether for birds or pigs — spots a worrying strain, the next steps tend to involve a chicken egg.
In the 1930s, scientists realized chicken eggs are a self-contained way to grow influenza virus and make vaccines.
Inject the egg with the virus and the pathogen grows just underneath the shell, with no risk of spreading it to humans or other animals. (Reminder: You must breathe in flu to catch it). Next, harvest those viruses, inactivate them with heat, and then extract the protein you need for your flu shot — in this case, hemagglutinin.
“Eggs are the way we make 95 percent of the world’s influenza vaccines today,” said Rick Bright, director of the Biomedical Advanced Research and Development Authority, or BARDA.
BARDA, a part of the Department of Health and Human Services, has been called the “the venture capital firm buried in the U.S. government.” It funds much of the nation’s work against chemical, biological and nuclear threats, which includes U.S. defenses against pandemic outbreaks.
“We’re a unique organization established specifically to bridge government with industry to make medical countermeasures, such as drugs, vaccines and diagnostics, that will protect Americans on the very worst day of their life,” Bright said.
In the case of pandemic influenza, BARDA coordinates the biomedical factories and farms that support vaccine production.
It takes 600,000 eggs a day to supply the seasonal flu vaccine process each year, Bright said. During a pandemic flu outbreak, the nation would ramp up to about 900,000 eggs every single day for six months to reinforce America’s vaccine supply. So at any given moment, BARDA and your tax dollars pay to keep an extra 300,000 fresh eggs on reserve.
BARDA does not disclose the location of the chicken farms that supply them.“They are part of our national security and critical infrastructure for our preparedness response to pandemic influenza,” Bright said. “In the event that there is an outbreak, that is where we send our best protective forces first, actually.”
But eggs come with issues. It’s a huge investment in space and livestock. A small percentage of the population is allergic to eggs, and thus, can react negatively to those vaccines. And sometimes the influenza virus will mutate while growing in an egg, meaning the final vaccine won’t exactly match what is plaguing people — and therefore, won’t provide solid protection.
So health officials like Bright are also looking at alternatives.
Since 2014, egg-free immunizations for influenza have been available thanks to laboratory methods that can raise hemagglutinin without chicken ovas. One of these two egg-free vaccines — FluBlok — relies on insect cells. The process is completed in petri dishes and beakers, so insects aren’t harmed.
“Those insect cells will start producing influenza vaccine very quickly,” Bright said. “We can save an additional month or so off the overall timeline.”
In 2018, the other egg-free vaccine — Flucelvax — performed 10 percent better during the seasonal flu outbreak than the egg-based vaccines.
“We are at least 20 or 30 years away from a truly universal influenza vaccine,” Bright said. “In the meantime, there is a wealth of work that we can do to make our existing influenza vaccines better, make them faster, make them more affordable.”
William Brangham, Jason Kane, Rachel Wellford, Courtney Norris and Devin Pinckard contributed to this reporting. This story was updated on June 21 to clarify the difference between Flucelvax and FluBlok.