“A journey into the origins of COVID-19 and the discovery of vaccines and potential cures . . . I learned so much that I didn’t know before—above all, I met the subtle warriors of the laboratory who are working to save all of us from the horror of new pandemics.”—Richard Preston, bestselling author of The Hot Zone and The Demon in the Freezer
One of Publishers Weekly’s top ten science books of the season
The urgency of the devastating COVID-19 pandemic has fixed humanity’s gaze on the present crisis. But the story of this pandemic extends far further back than many realize. In this engrossing narrative, epidemiologist Dan Werb traces the rising threat of the coronavirus family and the attempts by a small group of scientists who worked for decades to stop a looming viral pandemic.
When virologist Ralph Baric began researching coronaviruses in the 1980s, the field was a scientific backwater—the few variants that infected humans caused little more than the common cold. But when a novel coronavirus sparked the 2003 SARS epidemic, and then the MERS epidemic a decade later, Baric and his allies realized that time was running out before a pandemic strain would make the inevitable jump from animals to human hosts.
In The Invisible Siege, Werb unpacks the dynamic history and microscopic complexity of an organism that has wreaked cycles of havoc upon the world for millennia. Elegantly tracing decades of scientific investigation, Werb’s book reveals how Baric’s team of scientists hatched an audacious plan not merely to battle COVID-19 but to end pandemics forever. Yet as they raced to find a cure, they ran into a complicated nexus of science, ethics, industry, and politics that threatened to derail their efforts just as COVID-19 loomed ever larger.
The Invisible Siege is an urgent and moving testament to the unprecedented scientific movement to stop COVID-19—and a powerful look at the infuriating factors that threaten to derail discovery and leave the world vulnerable to the inevitable coronaviruses to come.
About the author
Dan Werb, PhD, is an award-winning writer and epidemiologist whose work has appeared in The New York Times, Salon, and elsewhere. He holds faculty appointments at the University of California San Diego and the University of Toronto.
Excerpt: The Invisible Siege: The Rise of Coronaviruses and the Search for a Cure (by (author) Dan Werb)
Only Occasional Ecstasy
February 14, 2003, Hong Kong, People’s Republic of China
It was Valentine’s Day, and Malik Peiris, the dutiful husband, was out with his wife at their favorite Indian restaurant. It was his first night off in weeks. Peiris, a Sri Lankan–born, Oxford-trained physician and virologist, had lived in Hong Kong since 1995 and was no stranger to emerging epidemics. In 1997, a deadly new strain of avian flu, H5N1, had caused hundreds of illnesses and dozens of deaths in his adopted city, and Peiris had distinguished himself by discovering the mechanism it was using to kill its hosts: a buildup of chemicals called cytokines, which were released by the immune system and ended up causing the body untold damage. But even for someone as well versed in beating back novel viruses as Peiris, the last few months had been bizarre.
Not that Peiris would have admitted as much. His reflexive Old World manners, expressed in a refined British-tinged accent, were accompanied by an innate warmth that put those around him at ease and concealed the intense pressure he put himself under. Peiris carried himself with a compact air, seemingly sewn into a neat suit and tie, with black hair prone to wildness framing a clear-eyed gaze. He betrayed little ego, downplaying with a quiet laugh the severity of the virological phenomena he battled. This amiability had imbued him with a capacity to take setbacks in stride, just as he had done when he was forced to flee Sri Lanka in the face of a growing political insurgency, a move that had eventually led him to his position in Hong Kong. Peiris did not, as a rule, dwell on misfortune. He was as apt to talk about the scientific friendships that forged the path to discovery as he was about how those discoveries might turn the tide in favor of humanity. The problem for Peiris was that in the first few months of 2003, the waves seemed to be rising higher and crashing harder than ever.
Two months earlier, in December 2002, Peiris had been called to two waterparks in Hong Kong that were home to flocks of ducks, swans, and greater flamingos. When he arrived, he encountered utter devastation: dozens of the birds had died, all of them felled by a new pathogen that didn’t match any previously detected virus. It was a morbid puzzle, and Peiris was determined to solve it. He immediately canceled his Christmas holidays and spent the ensuing months holed up in his lab at the University of Hong Kong, surrounded by a vast assortment of birds held in an adjacent animal containment facility. Wrestling with the avian sick and dead, he labored to extract samples and placed them inside petri dishes filled with tissue, hoping to get whatever microorganism had spread through the waterparks to replicate. It would take weeks of delicate coaxing, but the pathogen finally bloomed within the confines of his lab, allowing Peiris to isolate it from the surrounding avian tissue and cellular debris. Finally, Peiris gazed upon the specimen under a microscope; immediately, a deep anxiety welled up inside of him. It was a new virus, to be sure, but it looked disturbingly familiar. When he ran further tests, Peiris discovered that, to his horror, the virus was a lethal new strain of H5N1 avian flu, eerily similar to one that had caused dozens of deaths in his adopted city just five years earlier before Peiris spearheaded a citywide effort to contain it.
Peiris passed the next few weeks on pins and needles, waiting, exhausted and alarmed, for the inevitable epidemic to emerge. He had seen avian flu before, but that was cause for fear, not relief. Novel pathogens always started by infecting a cluster of cases, most often in domestic livestock, before the more efficient ones managed to spread across multiple species and into our own. Peiris knew that the waterpark outbreak had all the portents of an emerging killer flu: mass die-offs (the virus was deadly), airborne transmission (it could easily infect multiple individuals), and all of it occurring in environments that humans shared with animals (the virus had ample opportunities to jump from birds to humans). It was, Peiris believed, about to begin again.
And yet, by mid-February, despite his worst fears, the pathogen appeared to burn itself out, by all indications too unfit to replicate efficiently in humans. Peiris, at first cautiously, finally allowed himself to breathe a sigh of relief. The waterpark die-off was not the beginning of the pandemic that he and so many others had feared. It was just another passing virus that had failed to find purchase within the human race.
On Valentine’s Day 2003, seated in his favorite Indian restaurant, Peiris looked across the table at his wife and let the moment sink in. After all he had gone through, after all the fear of the last few months, this, finally, was a sliver of happiness.
Then his phone rang.
On the line was the head of the World Health Organization’s China mission. He had some troubling news. There was something happening in Guangdong, the Chinese province that neighbored Hong Kong. Hospitals were reporting a cluster of patients with an inexplicable and unusually severe flulike pneumonia. Peiris’s heart sank; just when he thought the avian flu outbreak had been self-contained, it appeared that it had indeed jumped the species barrier into humans. He had barely let himself relax, and it was already time to get right back to work.
By the next morning, all the major local newspapers had broken the story of the Guangdong pneumonia outbreak. While neighboring Hong Kong had come under Chinese rule in 1997, the Communist Party still handled its recently reclaimed territory as a pseudo-separate entity. Every day, close to one hundred thousand people crossed the boundary between Guangdong and Hong Kong, passing a formal border as they went. With the pneumonias spreading in hospital rooms and family homes, Peiris knew it was only a matter of time before it became a generalized epidemic. With a reputation burnished from his years of fighting avian flu, he convinced the local authorities to set up enhanced surveillance at the border, which saw agents screening the tens of thousands of crossing visitors for signs of illness. Eventually, they snared two cases: a father and son, both severely ill with pneumonia, who had recently returned from a trip to the mainland for the Lunar New Year festivities. There was a daughter, too, Peiris learned. Like her father and brother, she had become ill during the trip; unlike them, she had perished from her infection before making it back home. Peiris quickly ran samples from both the father and the son through laboratory tests he had designed to detect avian flu strains. When the results came back, he had what he believed was a smoking gun: both were infected with H5N1, the killer flu Peiris had battled in 1997 and that hadn’t been seen in humans since.
Peiris assumed that he had found his pathogen. He was wrong. Over the next few weeks, despite hundreds of people becoming ill with the same strange symptoms across Guangdong and Hong Kong, and despite countless tests at the border that separated them, no one else tested positive for H5N1. Remarkably, the father and son’s avian flu infection—and the sister’s death—was a red herring. With unexplained pneumonias proliferating, it was clear that there was some other unknown pathogen at work. Try as he might, though, Peiris could not identify the virus. He ran every conceivable lab test on samples from sick patients and from those who had succumbed to their illness. Hantavirus, adenoviruses, respiratory syncytial virus, parainfluenza—all were the usual second-line suspects whenever people got sick with respiratory symptoms that couldn’t be explained by influenza. All the tests came back negative. Making matters worse, Peiris couldn’t get the pathogen to replicate in the routine tissue cultures he grew other respiratory viruses in. That left him working with tiny amounts of virus, far too little to use for the battery of tests he needed to identify the culprit.
Unwilling to concede, Peiris experimented with less common animal tissues to see if he could find some that appealed to the unknown virus. After trying and failing and trying some more, he finally landed on a culture that the virus seemed to enjoy: fetal rhesus monkey kidney cells. Slowly at first, and then with accelerating ferocity, the virus tore through the tissue culture Peiris had gifted it. He finally had a workable specimen of the unknown pathogen.
“In this highly readable account, [Werb] gives due to those who toiled in obscurity to avert future pandemics only to run into frustrating political roadblocks.”—The Globe and Mail
“One of the most authoritative, comprehensive and, perhaps more importantly, readable books about the behind-the-scenes science of the COVID-19 pandemic and coronaviruses at large.”—The San Diego Union-Tribune
“A fascinating, sometimes terrifying, exploration of science and viruses . . . Through vivid storytelling, we see the deep roots of both scientific discovery and viral ecology, and how these are tangled with human ingenuity and folly.”—David George Haskell, author of The Forest Unseen and The Songs of Trees
“Through remarkable storytelling, Dan Werb illuminates the long history of the coronavirus family, how we were amply forewarned by the SARS and MERS epidemics, and how the science community has rallied to successfully take on SARS-CoV-2 and ultimately prevail over COVID.”—Eric Topol, director and founder of Scripps Research Translational Institute and author of Deep Medicine
“A page-turning and unsettling look at the history of coronaviruses . . . The light [Werb] sheds on scientists whose work has gone largely under the radar makes for a moving account. This is a unique and valuable addition to the expanding body of work on Covid-19.”—Publishers Weekly (starred review)