Breathless: The Scientific Race to Defeat a Deadly Virus

To some people it wasn’t surprising, the advent of this pandemic, merely shocking in the way a grim inevitability can shock. Those unsurprised people were infectious disease scientists. They had for decades seen such an event coming, like a small, dark dot on the horizon of western Nebraska, rumbling toward us at indeterminable speed and with indeterminable force, like a runaway chicken truck or an eighteen-wheeler loaded with rolled steel. The agent of the next catastrophe, they knew, would almost certainly be a virus. Not a bacterium as with bubonic plague, not some brain-eating fungus, not an elaborate protozoan of the sort that cause malaria. No, a virus—and, more specifically, it would be a “novel” virus, meaning not new to the world but newly recognized as infecting humans.

But if new to humans, from where would a “novel” virus emanate? Good question. Everything comes from somewhere, and new viruses in humans come from wild animals, sometimes by way of a domestic animal as intermediary. This sort of transfer, from nonhuman host to human, is known as spillover. Such viruses, including Marburg and rabies and Lassa and monkeypox, cause afflictions that are termed zoonoses—or zoonotic diseases. Most human infectious diseases are zoonotic, caused by animal-origin pathogens that reach us repeatedly (Nipah virus, spilling over from fruit bats in Bangladesh) or have reached us in the past (HIV-1 group M, the pandemic AIDS subtype, spilling over from a chimpanzee, once). Some are old to us (the plague bacterium, yellow fever virus) and hatefully familiar; some are as startlingly new and ferocious (Ebola virus) as a predatory alien in a movie.

A novel virus can be devastating if we have no vaccines to deflect it, no drugs to fight it, no history of past exposures to anything similar that might give us acquired immunity. A novel virus, if luck is good for the virus and bad for us, can go through the human population like a high-caliber bullet through marbled sirloin.

These scientists, the ones schooled in infectious diseases and savvy to zoonoses, further foresaw that it would likely be a particular kind of virus causing the next pandemic—a virus with a certain kind of genome, allowing for speedy evolution, a capacity to change and adapt fast. That genome would be written in RNA, not DNA. That is, a single-strand informational molecule, rather frangible, not DNA’s double helix. Never mind for now just what RNA is, how it works, or why a single-stranded RNA genome can be especially changeable and adaptive. Suffice to say that such speedy adapters include the influenzas and the coronaviruses, two groups of viruses with histories of bringing mayhem to humans. In the years before 2019, the word “coronavirus” was unfamiliar to most people, but it already carried an ominous timbre to infectious disease scientists.

One among those scientists is Yize (Henry) Li, a China-born virologist and immunologist, now an assistant professor at Arizona State University in Tempe. Yize Li is a round-faced young man who wears stylish rectangular glasses and a splash of black bangs hanging over his forehead. He did his doctorate at the Institut Pasteur in Shanghai, under the mentorship of a French professor, and took the name Henry for convenience in the French- and English-speaking milieus he has inhabited since. He came to the United States in 2013, for a postdoctoral fellowship with Susan R. Weiss, a veteran virologist at the University of Pennsylvania’s Perelman School of Medicine. Weiss is an authority on the coronaviruses, including SARS-CoV, the virus that caused the terrifying but abbreviated 2003 international outbreak of SARS (severe acute respiratory syndrome), infecting about eight thousand people and killing one in ten. Her lab also studies the MERS (Middle East respiratory syndrome) coronavirus, first recognized as a human pathogen in 2012, when a flurry of cases emerged on the Arabian Peninsula; MERS carries a fatality rate considerably higher than SARS, about 35 percent among confirmed cases. Li himself worked with Weiss both on the MERS virus and on a less dramatic coronavirus, one that causes hepatitis in mice.

He was there in Philadelphia during the latter days of December 2019 when he noticed an item on a Chinese news website, DiYiCaiJing, based in Shanghai. The item described an advisory note, supposedly confidential, that had recently circulated to staff at one Wuhan hospital and probably more than one. This advisory was said to come from the Wuhan Municipal Health Commission. The website’s reporter had somehow gotten hold of it and, contacting the commission, confirmed that it was from them. The note warned of an outbreak of an “unknown pathogen” that was bringing pneumonia cases to several hospitals in the city. Li promptly did what people do with interesting tidbits: he put the item on social media.

WeChat is an all-purpose Chinese app that combines the functions of Facebook, Instagram, WhatsApp, and Zoom. It has over a billion active users, including Henry Li and many other graduates and students of the Institut Pasteur in Shanghai. He relied on it to communicate with friends back in China. When he raised the Wuhan topic on WeChat, some of his contacts said, Yes, that’s a rumor; some said, Yes, it’s true. Then one of them threw down a trump card, posting an actual sequencing report that contained fragments of the genomes of multiple microbes, including bacteria and viruses, from several clinical samples. The samples—a throat swab here, a nose swab there, who knows—had been processed, RNA extracted, that RNA converted to DNA (for stability), then the DNA run through a sequencing machine in someone’s lab. The samples were “dirty,” as such samples commonly are, bearing smears and smudges of various genomes reflecting the microbial diversity present on human mucosal surfaces. But amid that distracting diversity, in at least one of these samples, was a patch of relevant data. This fragment was a linear sequence of roughly a thousand letters, a fraction of a genome but enough to be telling. It was contraband data. To you or to me such a sequence would have been just babble—attaaaggtttatacc for a thousand letters—but to scientists like Henry Li or Susan Weiss it spoke with chilling clarity. “I was amazed,” Li told me later, to see that it was “very, very similar to a SARS coronavirus.”

Weiss was on sabbatical in La Jolla, California, at that point, speaking with Li and other members of her lab in weekly Zoom meetings. During one of those calls in late December, to the best of her memory, Li mentioned that “something was really up” in Wuhan, China. “He probably told me,” Weiss recollected, when I spoke with her more than a year later, “ ‘Hey, there’s this coronavirus circulating.’ ” But the term itself, “coronavirus,” was not yet circulating in December 2019—not, at least, beyond such select networks of viral savvy.

Weiss returned to Philadelphia on January 2 and her crew promptly began ordering more N95 masks, the same kind they had been using in their study of the MERS virus (properly known as MERS-CoV). Other items of personal protective equipment (PPE), such as gloves and gowns, were already on backorder. Eventually they would add powered air purifying respirators (PAPRs), like space helmets without the suits. They were gearing up. She and her young colleagues had decided by then that they should work on this new coronavirus, and they knew they would need protection.