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Coronaviruses are named for their striking shape. They have a halo of “spike” proteins sticking out of a shell that protects the strand of genes that lets them replicate. The spikes attach to receptors on human cells, letting the coronavirus begin the process of copying itself.

Doctors had historically considered coronaviruses minor health threats compared to influenza, much less terrors like smallpox. The four coronaviruses known to infect humans before 2002 were generally associated with common colds.

Most respiratory virus researchers focused on influenza, whose dangers were more obvious. But the 2002-03 SARS epidemic, which killed about 800 people and caused a worldwide panic, and the MERS outbreak a decade later, made coronaviruses a hot topic among infectious disease researchers – and the policymakers who funded them.

Baric made sure everyone understood the risk of his favorite virus – and the need for well-funded research programs to reduce it.

Sure, neither SARS nor MERS appeared very transmissible, with MERS in particular seemingly requiring prolonged and close contact.

But their fatality rates were striking — 10 percent for SARS, 50 percent for MERS. With a few genetic modifications, similar coronaviruses might spread far more quickly, Baric argued.

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The best way to predict and ultimately reduce that risk would be to build coronaviruses more lethal and transmissible than any yet found in nature, Baric said in response to a question near the end of his first presentation:

The other way to do it… [is] make in essence recombinants where you drop the spike gene in different bat coronaviruses which you think may have appropriate properties that could be emergent, preemergent strains and characterize their ability to replicate in human cells…

Baric then acknowledged such work might be so risky that it might fall into the category of “dual-use experiments,” meaning research that militaries or terrorists might use to create deadlier biological weapons.

“Now, maybe dual-use experiments of concern, that’s another issue,” he said, with a slight giggle. (Yes, the video makes clear he does giggle, at approximately 45:55.)

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(Do-it-yerself coronaviruses, the Ralph Baric way! From a 2006 Baric paper titled “Synthetic Viral Genomics: Risks and Benefits for Science and Society.”)

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At a 2014 conference in Washington, D.C., Baric would also acknowledge his laboratory work outran any natural mutations that coronaviruses so far discovered in living animals had managed to produce.

After discussing three potential ways for the viruses to broaden their “host range” — that is, infect different species of animals, including humans — Baric acknowledged that two of the three “have only been identified using in vitro models, although the potential exists for similar mutants to emerge naturally in nature.”

Why do this work at all?

Baric and other scientists at the 2013 conference explained their work as necessary both to understand the potential threat from coronaviruses and to defuse it by helping research on antiviral drugs and vaccines.

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Never mind that the despite the publicity the SARS and MERS outbreaks had garnered, theor combined global death toll equaled roughly one day of flu deaths.

Never mind that vaccines for flu, the closest counterpart to coronaviruses, appeared mostly useless and that decades of research had not brought the world closer to better ones.

By making stickier spikes and fitter, more dangerous viruses, Baric would enable the development of better vaccines and antivirals. He would create an arms race, in order to win it.

Baric never put it quite this bluntly, but near the end of the conference – five hours and 26 minutes in, according to the video – he came close. “It’s basically structure-based antigen design,” he said. “You can blend S [spike] components… to provide a broader neutralizing response within that cluster.”

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Baric wasn’t just outlining potential research pathways in June 2013. He intended to do the work, and he did. In November 2015, he — along with a Chinese virologist named Shi Zhengli — published what became a notorious paper in Nature Medicine:

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Baric, Shi, and the other authors explained they had “generated” a “virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone.”

In other words, Baric had combined multiple coronaviruses to make one better at infecting humans. The new lab-made virus would “replicate efficiently in primary human airway cells,” the paper explained. “Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis.”

Baric’s co-author Shi was, of course, none other than the head of coronavirus research at the Wuhan Institutes of Virology, the lab from which Covid likely leaked in 2019. In 2018, Daszak’s EcoHealth Alliance attempted to get federal funding for a new project where the Wuhan lab and Baric would again collaborate on work to make coronaviruses more dangerous.

The United States government rejected the request as too risky; but whether Shi’s group went ahead with the research anyway and accidentally created Sars-Cov-2 is the most important question about Covid’s origins. The second most important is what Baric, Daszak, and other American researchers knew or suspected about Shi’s research as Covid exploded worldwide.

(In 2020, Nature Medicine added a defensive, if snippy, note to the article complaining that it was “being used as the basis for unverified theories that the novel coronavirus causing COVID-19 was engineered. There is no evidence that this is true.”)

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In 2016, Baric was the senior author on a paper in the Proceedings of the National Academy of Sciences that arguably went even further than the Nature Medicine paper. The research group he led had manipulated a coronavirus provided by Shi and found it “poised for human emergence.”

The authors explained that they had “construct[ed] chimeric and full-length zoonotic coronaviruses to evaluate emergence potential… the results indicate a significant threat posed by WIV1-CoV.” The lab-grown viruses “replicated efficiently in human airway cultures,” they wrote.

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Within the biomedical research community, research like Baric’s was controversial even at the time.

In a 2011 paper, virologists had shown that they could make avian influenza transmissible between ferrets, who are considered excellent animal models for humans. Avian flu does not easily infect humans, but it can be highly lethal when it does, so the avian flu experiment stirred serious concerns.

But the infectious disease researchers had an important ally: Tony Fauci, who wrote in the Washington Post in 2011 that the flu research was a “risk worth taking.”

Still, the obvious risks posed by highly infectious and dangerous viruses like smallpox had led the federal government to create what it called a list of select agents which required special precautions. Besides smallpox, the list included anthrax, plague, and the original SARS.

But MERS, despite its lethality, was not considered a “select agent”. And in the final moments of the June 24, 2013 conference, Ralph Baric called for the government not add it to the list.

“If you want fast movement forward, and you restrict it with select agent status, then that will have a very chilling effect on productivity,” Baric said. “I think somebody had to say it.”

MERS was never added to the select agent list.

And six-and-half-years later, the massive and deadly coronavirus epidemic that Baric had predicted – and worked so hard to stop – exploded around the globe.

(END OF PART TWO)

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PART ONE, IN CASE YOU MISSED IT AND YOU’RE A GLUTTON FOR PUNISHMENT

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