On Tuesday, it was clear that the “fact sheet” behind recent claims that COVID-19 originated in a Wuhan lab could not be trusted, and that, truthfully, we still don’t know the precise origin of the virus. We know it has ancestors among a pool of coronavirus that circulates in horseshoe bats and may have reached humans by way of pangolins as an intermediary host. But where the virus achieved the structure we know as SARS-CoV-2, including the ability to spread infection easily from human to human, remains unknown.

On Wednesday, President Joe Biden made a statement demanding a full investigation of those origins. According to Biden, U.S. intelligence on the subject has “coalesced around two likely scenarios.” Two elements of the intelligence community lean toward a scenario in which the virus was introduced into the human population through “human contact with an infected animal.” However, some other unidentified group within the intelligence community finds the idea of “a laboratory accident” more compelling. And the majority of agencies within the intelligence community “do not believe there is sufficient information to assess one to be more likely than the other.”

All of which stands in contrast to the “fact sheet” that remains posted on the web site of the U.S. Embassy in Georgia. That document—which was posted in the final days of Donald Trump on Jan. 15, and resurrected by a Wall Street Journal story over the last week—insists that the Wuhan Institute of Virology (WIV) was the scene of “secret military activity,” and that the U.S. government believes that “several researchers” became sick in the fall of 2019 with symptoms that are “consistent with both COVID-19 and common seasonal illnesses.” The implication of the sheet is not just that the virus emerged from the Wuhan lab, but that it was created by researchers engaged in “gain-of-function research to engineer chimeric viruses.”

That is definitely not what President Biden said on Wednesday. But the renewed commitment to get to the truth behind the origin is definitely a good thing.

SARS emerged in China in 2003. MERS appeared in Saudi Arabia 2012. Recent publications show that another coronavirus capable of infecting humans appeared in Haiti in 2014, and a fourth appeared in Malaysia in 2018. Fortunately, those last two viruses infected relatively small numbers of people and produced relatively mild disease—so much so that the first papers about both have only just been published. However, all of these viruses made the leap from animals to people. Several of them—including SARS, MERS, and the Malaysian virus—are also chimeric viruses that bear the hallmarks of being passed along through at least one intermediate host. (Palm civets in the case of SARS, camels in the case of MERS, and dogs in the case of the Malaysian virus.) 

That another coronavirus would make the leap from animals to humans in 2019 fits entirely with the pattern that’s been seen over the last decade. That the virus would be based on a virus found in bats after potentially passing through an intermediate host (SARS-CoV-2 contains sequences that appear to match coronavirus found in pangolins) also seems to fit with what’s been seen before.

The full genetic sequence of the virus was made available very early in the pandemic, less than two weeks after the first public announcement of cases around Wuhan. Researchers around the world immediately began examining that sequence (and both BioNTech and Moderna sequenced the RNA for their respective vaccines the following weekend). As noted in Nature Medicine back on March 17, 2020, those researchers came to a firm conclusion:

It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. … Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone.

SARS-CoV-2 attaches to human cells in a novel way that doesn’t match earlier speculation about how such attachment might happen, doesn’t contain any fingerprints of genetic manipulation, and shows none of the signs that might be expected if the virus had been engineered.

The Nature researchers looked at two possible routes for how the virus might have made its way to the first identified cases in a Wuhan hospital. One of those was through direct transmission from an animal; either a horseshoe bat or an illegally imported Malayan pangolin. The pangolin viruses in particular were found to very interesting. And this is a point worth noting: Though the analysis shows that the RaTG13 bat virus mentioned in the “fact sheet” is likely the several-times-removed relative of COVID-19, it’s the version found in pangolins that already contains several of the proteins unique to SARS-CoV-2 that allow it to bind to human cells. This, according to the researchers, “clearly shows that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2 is the result of natural selection.” That spike protein was found in wild virus taken from pangolins.

So, if SARS-CoV-2 made its way directly from animals to humans, it likely wasn’t because anyone at the Wuhan seafood market was peddling bats on a stick, but because someone in the city of over 11 million was peddling poor, beleaguered pangolins, which have become endangered mostly because of their use in folk medicine as well as for their scales and meat, and are widely trafficked across China.

Neither of these viruses is anything like a perfect match for SARS-CoV-2. They may not even be direct ancestors of the virus that spread around the world. However, the researchers note that these wild viruses are “massively undersampled” and that “mutations, insertions and deletions” at a specific site in the SARS-CoV-2 virus show that the differences “can arise by a natural evolutionary process.”

In other words, there is no evidence that SARS-CoV-2 was deliberately engineered. And it didn’t need to be. The natural pool of emerging viruses is easily adequate to explain all the features seen.

The researchers also looked at another scenario that gets little consideration: What if an ancestor of SARS-CoV-2 made the jump into humans, perhaps one that caused little noticeable disease, and it was evolution of that virus within humans that led to the virus that causes COVID-19?

This is apparently what happened with MERS. Just as pangolins carry a virus similar to SARS-CoV-2, dromedary camels carry a virus similar to MERS. This virus apparently managed to infect individuals a number of times before one of these infections resulted in a mutation that allowed it to spread person to person. That single person then became the source of all MERS cases, but the virus developed in the human, not the camel.

The situation with MERS, in which all known early human cases share a nearly identical genetic signature, appears to match what’s seen in SARS-CoV-2, which could make it likely that a virus—sourced from pangolins but capable of infecting humans—made that jump several times. And it was only in one of those human hosts where the final mutations took place that made the virus into SARS-CoV-2. Even then, a pre-coronavirus might have sputtered along in humans for several viral generations before hitting on the mutations and adaptations that sent people in Wuhan to the hospital and touched off a global pandemic.

Finally, those researchers also looked at the possibility of laboratory escape. That possibility is certainly real. There are, after all, documented cases of SARS and even smallpox resulting from laboratory escapes … and few substances on Earth are treated with the sort of dread respect as the remaining samples of smallpox.

But while the scientists can’t eliminate the possibility that the first case of SARS-CoV-2 escaped a facility in the body of a researcher, they are definitive in saying that the features of the virus all but rule out the possibility that the virus was developed “in culture.” The changes between the virus and the wild viruses “argues against culture-based scenarios.” Instead, the features of the virus “suggest the involvement of an immune system.” SARS-CoV-2 evolved within living animals, almost certainly in the wild.

So… once again, could the virus that causes SARS-CoV-2 have been introduced to the population of Wuhan by laboratory error at the virology institute in that city? Yes, though there remains no evidence that this is the case. Could the virus have been in some sense built at that lab by combining features of bat and pangolin viruses in some kind of “gain-of-function” research? No. Almost certainly not.

There are now at least four other examples of coronaviruses emerging from animal to human populations in the last 20 years. Two of those four generated deadly epidemics. None of those viruses required a boost from human researchers or the assistance of a human lab to begin their spread in the population. SARS-CoV-2 could be an exception, but the evidence so far all points to it to being just No. 5 in a series.

Unnamed sources in unnamed intelligence agencies citing the idea that unnamed researchers at the WIV became ill with symptoms that could have been COVID-19 … or the flu … or a bad cold doesn’t make the possibility of a lab escape any stronger. However, a full investigation and public release of data on an area of vital national concern would definitely be a good thing.

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