From the moment the novel
coronavirus, SARS-CoV-2, emerged in Wuhan, China, scientists and the broader public have sought answers to some fundamental questions: Where did this virus come from? How did the pandemic start? From the early days, experts have considered two possibilities. Either the virus somehow escaped from a laboratory, perhaps the Wuhan Institute of Virology, or, like countless viruses throughout history, it arrived through zoonotic spillover, jumping from animals to humans.
More than a year later, we still don’t know exactly what happened. Though governments and news organizations have focused more attention recently on the notion that the virus
leaked from a lab, it’s unclear that we’ll ever identify a theory that satisfies everyone as to how SARS-CoV-2 emerged. Ironically, given the recent prominence of the lab escape theory, the questions the world wants answered about the virus — and the astonishingly fast development of the vaccines that can quash the pandemic — depend entirely on research conducted in labs like the Wuhan Institute of Virology and across the world over the past several decades. This fundamental research underpins our ability to prepare for and respond to pandemics. We need to know what’s out there and what kind of viral threats we face. The only way to do that is to go where the viruses are, with our colleagues who are already there.
In March 2020, a group of renowned evolutionary virologists analyzed the genome sequence of SARS-CoV-2 and
found it was overwhelmingly likely that this virus had never been manipulated in any laboratory. Like the earlier coronaviruses SARS-CoV and MERS-CoV, they theorized, it “spilled over” from its natural reservoir host (bats) to a new one (humans). Viruses jump species frequently, with unpredictable consequences. Often a virus hits an evolutionary dead end if it cannot adapt to the new host rapidly enough to be transmitted again. Sometimes, however, it can. Clues that reveal this scenario can be found by analyzing the sequence of the virus genome, and that’s exactly what this study did.
The study carefully examined whether key elements of the virus, particularly the spike protein on its surface, appeared engineered. They did not. The spike didn’t optimally bind to its receptor, ACE-2, and the interaction between the two proteins was unpredictable even using the most advanced computer algorithms. Another key feature
often cited as evidence of laboratory origin is the furin cleavage site, where the spike protein is cut in half to “activate” viral material for entry into cells. The viruses most closely related to SARS-CoV-2 don’t have this site, but many others do, including other human coronaviruses. The furin site of SARS-CoV-2 has odd features that no human would design. Its sequence is suboptimal, meaning its cleavage by the enzyme furin is relatively inefficient. Any skilled virologist hoping to give a virus new properties this way would insert a furin site known to be more efficient. The SARS-CoV-2 site has more of the hallmarks of sloppy natural evolution than a human hand. Indeed, a
timely analysis last year showed convincingly that it is a product of genetic recombination, a natural feature of coronavirus replication and evolution.
Unfortunately, the pandemic has provided many opportunities to observe SARS-CoV-2 evolution in humans as it unfolds — and confidence in its natural origin has grown over time. The molecular handshake between SARS-CoV-2 and ACE-2, seemingly unique in early 2020, turns out to be found in
several related viruses and has since evolved to be a better fit. Its ability to infect human cells also turns out to be unremarkable. A related virus
discovered in pangolins infects human cells even more readily than SARS-CoV-2. The virus behind the pandemic may be special in its impact on our lives and the global economy, but the way it infects us isn’t unique at all.
The evolutionary trajectory of SARS-CoV-2 further undermines claims that the virus is obviously artificial and designed for human transmission. Early in the pandemic, a mutation called D614G took hold and spread rapidly around the world, showing that the virus was adapting to its host from the very beginning. Since then, mutations in the region of the spike protein that binds ACE-2, as well as near the furin cleavage site, show continued adaptation. Several of these are found repeatedly in different variants of concern and almost certainly contribute to increased transmissibility. SARS-CoV-2 continues to evolve. It wasn’t perfectly tuned for humans when it appeared, just good enough.
The epidemiological evidence in the
World Health Organization’s origins mission report from this spring further bolsters the natural-origin hypothesis. Among early cases, 55 percent had had exposure to wildlife markets, and the growth of the outbreak over time, both in cases and excess deaths, clearly shows that the neighborhood surrounding the Huanan market was the initial center of the epidemic in Wuhan. It’s true that 45 percent of cases could not be linked to a market, but the silent spread of SARS-CoV-2 that has made it so hard to control also makes it difficult to rule out such connections. Yes, the WHO’s mission was imperfect and hampered by political forces in China and elsewhere; even the organization’s director general, Tedros Adhanom Ghebreyesus, has nodded to those limitations by calling for a more thorough examination of the possibility of a lab escape. We don’t disagree about the benefits of doing so, and perhaps the U.S. government’s 90-day intelligence review will turn up compelling new information. We must consider every possibility — but our priorities should be guided by what is most likely. There are still missing pieces of data, including those unlinked cases and inadequate animal sampling, but most of the data we do have points heavily toward natural origin.
bit.ly
), they should be offering that deal (man! 
) around the crystal-bothering shops and headshops of Glastonbury very soon 
was on offer ..... there might even become unexpected actual competition between loons and the sane for jabs, around certain parts of Somerset!! 
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