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University of Nebraska Medical Center

What we know about the origin of covid-19, and what remains a mystery

Washington Post

The precise origin of SARS-CoV-2, the coronavirus that causes covid-19, remains unknown and continues to be a source of contentious debate. Two theories dominate the conversation: a natural spillover from infected animals, and a “lab leak” associated with coronavirusresearch in Wuhan, China, the city where the first cases of an unusual pneumonia-like illness were reported.

President Biden in May 2021 asked intelligence agencies to probe the origins of the virus, but they were unable to reach a consensus. Most favored, with “low confidence,” the natural spillover theory. Peer-reviewed scientific papers published last year bolstered the case that the virus came from animals sold at the Huanan Seafood Wholesale Market inWuhan.

On March 20, an international team of scientists posted online a report, not yet peer reviewed or published in a journal, arguing that newly revealed data from environmental swabs at the market confirm that multiple animal species were present at the market, including raccoon dogs, known to be capable of coronavirus infections. The report claims that the new data “contribute to and underscore the large body of evidence supporting a natural origin of SARS-CoV-2.”

On April 5, Chinese scientists published in the journal Nature their long-awaited report on the market, confirming the detection of live virus in the part of the market where many animal species were sold. But the report said the data does not prove that any of those animals were infected. Some animals, including stray cats and rats, were tested at the market and none showed signs of infection. No raccoon dogs were tested, however.

“The origin of the virus cannot be determined from all the analyses available so far,” the report concluded.

Critics of the natural spillover theory point out that the investigators at the market did not find any virus-infected animals that could have been the source of the outbreak. That fact was highlighted in a report issued last year by Republican staff on a Senate committee looking into the origin of the virus. The report also raised questions about safety protocols at a Wuhan laboratory. While not ruling out a natural spillover, the Republican staffers concluded that a “research-related incident” was the “most likely” origin. Now House Republicans, newly in charge of their chamber, have opened a fresh probe of covid’s origin.

What new evidence has emerged about the origin of covid-19?

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The pandemic’s origin remains unknown. But new information has emerged, and this is such an explosive issue that incremental developments can generate big headlines.

As first reported by the Atlantic, newly released raw data from China suggests that raccoon dogs sold in the Huanan Seafood Market could have been the source of the viral spillover. Raccoon dogs are small, fox-like mammals that have been sold illegally in Chinese markets.

Scientists have considered the animals prime suspects in the pandemic’s origin, in part because they are capable of infections with coronaviruses such as SARS-CoV-2, which causes covid-19. Until recently, however, there was no conclusive evidence that raccoon dogs were among the animals sold in the Wuhan market when the outbreak began.

That changed early this year when French scientist Florence Débarre noticed that new genomic sequences from Chinese researchers had been uploaded to a global database of information about influenza and the coronavirus. The data came from swabs of surfaces in the market taken by investigators in early 2020, after the market had been closed and animals removed. Scientists say the swabs show genetic markers of the virus and a number of animals that could have been intermediate hosts for the virus.

“This included DNA from wild raccoon dogs, Malaysian porcupine, and bamboo rats among others, in SARS-CoV-2 positive environmental samples,” according to WHO’s Scientific Advisory Group for the Origins of Novel Pathogens (SAGO), in a March 18 summary of the new developments.

One swab struck scientists as particularly suggestive: It showed genetic traces from the coronavirus along with raccoon dog DNA, and it was obtained in a stall where a visiting scientist had observed a raccoon dog for sale in 2014. Débarre and an international team of scientists swiftly began an analysis of the new data.

“Just like a crime scene where you have DNA from a particular person, we have DNA from animals that we most suspect were the intermediates,” University of Arizona evolutionary virologist Michael Worobey told The Washington Post.

But this remains a circumstantial case. “We haven’t showed that raccoon dogs or any other animals were infected at the market — the data can’t show that,” Worobey said.

The new report from China reiterates that point and says the crowded market may have been the site of a superspreader event but not the place where the virus first infected people.

“It remains possible that the market may acted as an amplifier of transmission due to the high number of visitors every day, causing many of the initially identified infection clusters in the early stages of the outbreak,” the new report states. “[E]ven if the animals were infected, our study does not rule out that human-to-animal transmission occurred. considering the sampling time was after the human infection within the market as reported retrospectively. Thus, the possibility of potential introduction of the virus to the market through infected humans, or cold chain products, cannot be ruled out yet.”

How does the new data affect the theory that the virus escaped from a lab?

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This latest data point, coming from scientists who have long argued for a market origin, is unlikely to shift the views of those who favor the lab-leak theory.

That theory got a boost earlier in the year, when the intelligence community produced an updated version of its 2021 report to Biden. By and large that assessment has not changed. But The Wall Street Journal reported on Feb. 26 that the updated assessment reveals the Energy Department has shifted from a neutral stance on the virus’ origin to one favoring, with “low confidence,” a lab leak.

The updated intelligence report remains classified, so it is unclear why the Energy Department changed its view.

Four other agencies and the National Intelligence Council continue to favor the natural origin with “low confidence.” The FBI, however, continues to state with “moderate confidence” that it favors a laboratory origin. “The FBI has for quite some time now assessed that the origins of the pandemic are most likely a potential lab incident in Wuhan,” FBI Director Christopher A. Wray said in a Fox News interview Feb. 28.

Why is the Energy Department involved in covid investigations?

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The Energy Department runs major national laboratories and spends billions every year on scientific research, including work on quantum physics and fusion energy. The covid origins analysis was performed by a little-known scientific team that specializes in emerging security threats, The Post has reported.

National security adviser Jake Sullivan told CNN on Sunday that Biden asked for the national labs to be involved in the covid origin investigation “because he wants to put every tool at use to be able to figure out what happened here.”

When asked about its new stance on a lab leak, adepartment spokesperson referred questions to the intelligence agencies, saying, “the Department of Energy continues to support the thorough, careful, and objective work of our intelligence professionals in investigating the origins of covid-19, as the President directed.”

What evidence exists for a lab leak?

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The Wuhan Institute of Virology is the primary focus of the lab-leak conjectures, because it is a major research center that did extensive work on coronaviruses.

Many versions of the lab-leak theory require some level of secrecy by researchers in China. But there are also scenarios that involve an accidental release of the virus without anyone realizing it. For example, researchers at the institute collect wild bats, which are ancestral sources of coronaviruses. Someone involved in this process could have inadvertently introduced the virus into the Wuhan population.

Proponents of a lab leak also point to experiments at the lab that manipulate viruses in ways that could make them more transmissible — “gain of function” experimentation. The goal of such research is to understand how a pathogen might evolve to become more of a threat, but critics have decried this as inviting disaster.

On March 8, Robert Redfield, the director of the Centers for Disease Control and Prevention during the Trump administration, testified at a GOP-led House hearing that the pandemic almost certainly began with a lab leak from a facility conducting gain-of-function research.

Supporters of the lab-leak theory have pointed to an unfunded proposal for an experiment that, they argue, could be a recipe for making a virus like SARS-CoV-2. And one recent experiment at the Wuhan Institute of Virology, funded in part by the National Institutes of Health through a grant to the organization EcoHealth Alliance, has come under special scrutiny, creating a political headache for NIH officials.

That experiment could not have produced SARS-CoV-2, according to scientists who analyzed it. But critics believe this kind of viral manipulation — or some other type of experimentation that creates novel viruses or enhances their transmissibility — could have led to the creation of SARS-CoV-2.

That idea remains speculative. There is no evidencethat the virus or its progenitorwas in any laboratory before the outbreak in late 2019.

Chinese scientists have said they were not working with the virus. Chinese officials, however, have not been cooperative with international investigators, and have instead floated improbable theories, such as that the virus entered China in a shipment of frozen fish, or as the result of American biological research efforts.

The WHO has probed the origin of the virus without reaching a conclusion and has struggled with political obstacles to the inquiry. On Feb. 14, Nature reported that the WHO had shelved its efforts, citing these difficulties.

However, a WHO spokesperson said in an email March 1 that the organization will “keep examining all available scientific evidence that would help us advance the knowledge on the origin of SARS CoV 2 and we call on China and the scientific community to undertake necessary studies in that direction. Until we have more evidence all [hypotheses]are still on the table.”

What is the evidence for a natural origin?

Many experts note that a natural origin would line up with the history of pandemics, which typically start with spillovers from animals — no laboratory help required. Scientists think SARS, the previous coronavirus outbreak in China that began in 2002, came from a spillover event.It has been genetically traced back to horseshoe bats, and it infected humans via an intermediate species: civet cats sold in markets.

Data from China shows that a large percentage of early SARS-CoV-2 infections were clustered around the Huanan Seafood Market. Researchers promoting a lab-leak origin of the pandemic, as well as Chinese scientists who favor a foreign origin, have said the market could have been merely the scene of a superspreader event.

But scientists favoring the market origin point out that, of all the possible locations in Wuhan where the first cluster of infections appeared, this one occurred in a market where animals potentially capable of transmitting the virus were sold.

Two papers published last summer in the journal Science argued in favor of the market as the epicenter of the outbreak.

Based on genomic analysis of early infections, one paper argues there were at least two separate spillover events in the market, producing two distinct lineages of the virus. The other paper says the geographical clustering of early infections, combined with environmental samples showing traces of the virus in areas where animals were sold, point clearly to the market as the epicenter of the outbreak.

But the scientists favoring the market origin acknowledge that there are missing pieces in the narrative. They have not identified which animals were infected or where they came from. The market was closed and cleaned and the animals culled within a few days of the outbreak.

“Everything upstream of this — which animals, where did they come from, how it’s all connected — is completely unknown at this stage,” Kristian Andersen, an infectious-disease researcher at Scripps Research and co-author of both papers, said in a media briefing at the time.

So will we ever know the origin of covid?

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The origin of covid has become so polarizing that it may never be resolved to widespread satisfaction. Because the issue is politicized, it is vulnerable to motivated reasoning — interpreting facts to fit a preferred narrative.

The struggle within the intelligence community to reach a consensus is revelatory in its own way: Investigators with different interests or expertise, who are working on separate research teams, may look at the same collection of intelligence and still reach contradictory conclusions.

The narrative could change dramatically with a new scientific or investigatory revelation that produces unassailable and unambiguous evidence. For example, a whistleblower in a laboratory could reveal credible evidence of the presence of SARS-CoV-2 in a research facility before the outbreak. Or, researchers could find the progenitor of SARS-CoV-2 in archived tissue samples taken from commercially trafficked animals.

In the meantime, the contentious situation has put increased attention on whether laboratory research on viruses is worth the risk of an accident.

There is a significant, ongoing divide among scientists about the safety of laboratory research that involves the manipulation of pathogens. Lab leaks can happen. Research on viruses may involve manipulating them in ways that could, in theory, lead to an accident — and a pandemic.

Because of ongoing concerns about research safety, the National Science Advisory Board for Biosecurity has issued a preliminary report calling for tightening of oversight of research on potential pathogens. Those changes have been in process for many years and are not a response to the lab-leak theory. But questions about covid’s origin inevitably shadow any discussion about how to balance the risks and benefits of pathogen research.

On Feb. 26, Gerald Parker, a Texas A&M University professor and chair of the biosafety board, wrote on Twitter, “We have a moral obligation to determine to the best of our ability how SARS2 emerged to cause the worst pandemic in over 100 years.”

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