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Opinion Guest Essay

Why the Pandemic Probably Started in a Lab, in 5 Key Points

Illustration by Mike McQuade. Source photographs by Getty Images.

By Alina Chan

Dr. Chan is a molecular biologist at the Broad Institute of M.I.T. and Harvard, and a co-author of “Viral: The Search for the Origin of Covid-19.”

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This article has been updated to reflect news developments.

On Monday, Dr. Anthony Fauci returned to the halls of Congress and testified before the House subcommittee investigating the Covid-19 pandemic. He was questioned about several topics related to the government’s handling of Covid-19, including how the National Institute of Allergy and Infectious Diseases, which he directed until retiring in 2022, supported risky virus work at a Chinese institute whose research may have caused the pandemic.

For more than four years, reflexive partisan politics have derailed the search for the truth about a catastrophe that has touched us all. It has been estimated that at least 25 million people around the world have died because of Covid-19, with over a million of those deaths in the United States.

Although how the pandemic started has been hotly debated, a growing volume of evidence — gleaned from public records released under the Freedom of Information Act, digital sleuthing through online databases, scientific papers analyzing the virus and its spread, and leaks from within the U.S. government — suggests that the pandemic most likely occurred because a virus escaped from a research lab in Wuhan, China. If so, it would be the most costly accident in the history of science.

Here’s what we now know:

1 The SARS-like virus that caused the pandemic emerged in Wuhan, the city where the world’s foremost research lab for SARS-like viruses is located.

  • At the Wuhan Institute of Virology, a team of scientists had been hunting for SARS-like viruses for over a decade, led by Shi Zhengli.
  • Their research showed that the viruses most similar to SARS‑CoV‑2, the virus that caused the pandemic, circulate in bats that live roughly 1,000 miles away from Wuhan. Scientists from Dr. Shi’s team traveled repeatedly to Yunnan province to collect these viruses and had expanded their search to Southeast Asia. Bats in other parts of China have not been found to carry viruses that are as closely related to SARS-CoV-2.

Sources: Sarah Temmam et al., Nature; SimpleMaps

Note: Cities shown have a population of at least 200,000.
A map showing the closest known relatives of SARS-CoV-2 in a mine in the Yunnan province of China and in a cave in northern Laos.
A map showing the hundreds of large cities in China and the surrounding region.
A map showing the 950 miles between Yunnan and Wuhan, and the 1,190 miles between Laos and Wuhan. There are many cities in between.
  • Even at hot spots where these viruses exist naturally near the cave bats of southwestern China and Southeast Asia, the scientists argued, as recently as 2019, that bat coronavirus spillover into humans is rare.
  • When the Covid-19 outbreak was detected, Dr. Shi initially wondered if the novel coronavirus had come from her laboratory, saying she had never expected such an outbreak to occur in Wuhan.
  • The SARS‑CoV‑2 virus is exceptionally contagious and can jump from species to species like wildfire. Yet it left no known trace of infection at its source or anywhere along what would have been a thousand-mile journey before emerging in Wuhan.

2 The year before the outbreak, the Wuhan institute, working with U.S. partners, had proposed creating viruses with SARS‑CoV‑2’s defining feature.

  • Dr. Shi’s group was fascinated by how coronaviruses jump from species to species. To find viruses, they took samples from bats and other animals, as well as from sick people living near animals carrying these viruses or associated with the wildlife trade. Much of this work was conducted in partnership with the EcoHealth Alliance, a U.S.-based scientific organization that, since 2002, has been awarded over $80 million in federal funding to research the risks of emerging infectious diseases.
  • The laboratory pursued risky research that resulted in viruses becoming more infectious: Coronaviruses were grown from samples from infected animals and genetically reconstructed and recombined to create new viruses unknown in nature. These new viruses were passed through cells from bats, pigs, primates and humans and were used to infect civets and humanized mice (mice modified with human genes). In essence, this process forced these viruses to adapt to new host species, and the viruses with mutations that allowed them to thrive emerged as victors.
  • By 2019, Dr. Shi’s group had published a database describing more than 22,000 collected wildlife samples. But external access was shut off in the fall of 2019, and the database was not shared with American collaborators even after the pandemic started, when such a rich virus collection would have been most useful in tracking the origin of SARS‑CoV‑2. It remains unclear whether the Wuhan institute possessed a precursor of the pandemic virus.
  • In 2021, The Intercept published a leaked 2018 grant proposal for a research project named Defuse, which had been written as a collaboration between EcoHealth, the Wuhan institute and Ralph Baric at the University of North Carolina, who had been on the cutting edge of coronavirus research for years. The proposal described plans to create viruses strikingly similar to SARS‑CoV‑2.
  • Coronaviruses bear their name because their surface is studded with protein spikes, like a spiky crown, which they use to enter animal cells. The Defuse project proposed to search for and create SARS-like viruses carrying spikes with a unique feature: a furin cleavage site — the same feature that enhances SARS‑CoV‑2’s infectiousness in humans, making it capable of causing a pandemic. Defuse was never funded by the United States. However, in his testimony on Monday, Dr. Fauci explained that the Wuhan institute would not need to rely on U.S. funding to pursue research independently.
The Wuhan lab ran risky experiments to learn how SARS-like viruses might infect humans. Their research started by collecting SARS-like viruses from bats and other wild animals, as well as from people exposed to them.
Next, they would identify high-risk viruses by screening for spike proteins that facilitate infection of human cells.
Then they would create new coronaviruses by inserting spike proteins or other features that could make the viruses more infectious in humans.
Finally, they would infect human cells, civets and humanized mice with the new coronaviruses, to determine how dangerous they might be.
  • While it’s possible that the furin cleavage site could have evolved naturally (as seen in some distantly related coronaviruses), out of the hundreds of SARS-like viruses cataloged by scientists, SARS‑CoV‑2 is the only one known to possess a furin cleavage site in its spike. And the genetic data suggest that the virus had only recently gained the furin cleavage site before it started the pandemic.
  • Ultimately, a never-before-seen SARS-like virus with a newly introduced furin cleavage site, matching the description in the Wuhan institute’s Defuse proposal, caused an outbreak in Wuhan less than two years after the proposal was drafted.
  • When the Wuhan scientists published their seminal paper about Covid-19 as the pandemic roared to life in 2020, they did not mention the virus’s furin cleavage site — a feature they should have been on the lookout for, according to their own grant proposal, and a feature quickly recognized by other scientists.
  • Worse still, as the pandemic raged, their American collaborators failed to publicly reveal the existence of the Defuse proposal. The president of EcoHealth, Peter Daszak, recently admitted to Congress that he doesn’t know about virus samples collected by the Wuhan institute after 2015 and never asked the lab’s scientists if they had started the work described in Defuse. In May, citing failures in EcoHealth’s monitoring of risky experiments conducted at the Wuhan lab, the Biden administration suspended all federal funding for the organization and Dr. Daszak, and initiated proceedings to bar them from receiving future grants. In his testimony on Monday, Dr. Fauci said that he supported the decision to suspend and bar EcoHealth.
  • Separately, Dr. Baric described the competitive dynamic between his research group and the institute when he told Congress that the Wuhan scientists would probably not have shared their most interesting newly discovered viruses with him. Documents and email correspondence between the institute and Dr. Baric are still being withheld from the public while their release is fiercely contested in litigation.
  • In the end, American partners very likely knew of only a fraction of the research done in Wuhan. According to U.S. intelligence sources, some of the institute’s virus research was classified or conducted with or on behalf of the Chinese military. In the congressional hearing on Monday, Dr. Fauci repeatedly acknowledged the lack of visibility into experiments conducted at the Wuhan institute, saying, “None of us can know everything that’s going on in China, or in Wuhan, or what have you. And that’s the reason why — I say today, and I’ve said at the T.I.,” referring to his transcribed interview with the subcommittee, “I keep an open mind as to what the origin is.”

3 The Wuhan lab pursued this type of work under low biosafety conditions that could not have contained an airborne virus as infectious as SARS‑CoV‑2.

  • Labs working with live viruses generally operate at one of four biosafety levels (known in ascending order of stringency as BSL-1, 2, 3 and 4) that describe the work practices that are considered sufficiently safe depending on the characteristics of each pathogen. The Wuhan institute’s scientists worked with SARS-like viruses under inappropriately low biosafety conditions.

Note: ​​Biosafety levels are not internationally standardized, and some countries use more permissive protocols than others.
In the U.S., virologists generally use stricter Biosafety Level 3 protocols, which involves using personal respirators and biosafety cabinets in combination to avoid inhaling an airborne virus, as well as wearing gloves and wraparound gowns to prevent direct contact.
The Wuhan lab was regularly working with SARS-like viruses at Biosafety Level 2, which involves work done in the open air and doesn’t require masks, allowing for inhalation of viral particles, and much less protective equipment worn on the body that allows for direct skin contact.
  • In one experiment, Dr. Shi’s group genetically engineered an unexpectedly deadly SARS-like virus (not closely related to SARS‑CoV‑2) that exhibited a 10,000-fold increase in the quantity of virus in the lungs and brains of humanized mice. Wuhan institute scientists handled these live viruses at low biosafety levels, including BSL-2.
  • Even the much more stringent containment at BSL-3 cannot fully prevent SARS‑CoV‑2 from escaping. Two years into the pandemic, the virus infected a scientist in a BSL-3 laboratory in Taiwan, which was, at the time, a zero-Covid country. The scientist had been vaccinated and was tested only after losing the sense of smell. By then, more than 100 close contacts had been exposed. Human error is a source of exposure even at the highest biosafety levels, and the risks are much greater for scientists working with infectious pathogens at low biosafety.
  • An early draft of the Defuse proposal stated that the Wuhan lab would do their virus work at BSL-2 to make it “highly cost-effective.” Dr. Baric added a note to the draft highlighting the importance of using BSL-3 to contain SARS-like viruses that could infect human cells, writing that “U.S. researchers will likely freak out.” Years later, after SARS‑CoV‑2 had killed millions, Dr. Baric wrote to Dr. Daszak: “I have no doubt that they followed state determined rules and did the work under BSL-2. Yes China has the right to set their own policy. You believe this was appropriate containment if you want but don’t expect me to believe it. Moreover, don’t insult my intelligence by trying to feed me this load of BS.”
  • SARS‑CoV‑2 is a stealthy virus that transmits effectively through the air, causes a range of symptoms similar to those of other common respiratory diseases and can be spread by infected people before symptoms even appear. If the virus had escaped from a BSL-2 laboratory in 2019, the leak most likely would have gone undetected until too late.
  • One alarming detail — leaked to The Wall Street Journal and confirmed by current and former U.S. government officials — is that scientists on Dr. Shi’s team fell ill with Covid-like symptoms in the fall of 2019. One of the scientists had been named in the Defuse proposal as the person in charge of virus discovery work. The scientists denied having been sick.

4 The hypothesis that Covid-19 came from an animal at the Huanan Seafood Market in Wuhan is not supported by strong evidence.

  • In December 2019, Chinese investigators assumed the outbreak had started at a centrally located market frequented by thousands of visitors daily. This bias in their search for early cases meant that cases unlinked to or located far away from the market would very likely have been missed. To make things worse, the Chinese authorities blocked the reporting of early cases not linked to the market and, claiming biosafety precautions, ordered the destruction of patient samples on January 3, 2020, making it nearly impossible to see the complete picture of the earliest Covid-19 cases. Information about dozens of early cases from November and December 2019 remains inaccessible.
  • A pair of papers published in Science in 2022 made the best case for SARS‑CoV‑2 having emerged naturally from human-animal contact at the Wuhan market by focusing on a map of the early cases and asserting that the virus had jumped from animals into humans twice at the market in 2019. More recently, the two papers have been countered by other virologists and scientists who convincingly demonstrate that the available market evidence does not distinguish between a human superspreader event and a natural spillover at the market.
  • Furthermore, the existing genetic and early case data show that all known Covid-19 cases probably stem from a single introduction of SARS‑CoV‑2 into people, and the outbreak at the Wuhan market probably happened after the virus had already been circulating in humans.

Source: Lv et al., Virus Evolution (2024), as reproduced by Jesse Bloom
An analysis of SARS-CoV-2’s evolutionary tree shows how the virus evolved as it started to spread through humans.
The viruses that infected people linked to the market fall partway down this tree, suggesting that they were most likely not the earliest form of the virus that seeded the pandemic.
  • Not a single infected animal has ever been confirmed at the market or in its supply chain. Without good evidence that the pandemic started at the Huanan Seafood Market, the fact that the virus emerged in Wuhan points squarely at its unique SARS-like virus laboratory.

5 Key evidence that would be expected if the virus had emerged from the wildlife trade is still missing.

In the SARS and MERS epidemics, scientists were able to find key pieces of evidence that demonstrated a natural origin of the virus. They found infected animals, the earliest human cases were exposed to animals, there was antibody evidence in animal traders, ancestral variants were found in animals, and there was documented trade of host animals.
For SARS-CoV-2, all of these pieces of evidence are missing.
  • Despite the intense search trained on the animal trade and people linked to the market, investigators have not reported finding any animals infected with SARS‑CoV‑2 that had not been infected by humans. Yet, infected animal sources and other connective pieces of evidence were found for the earlier SARS and MERS outbreaks as quickly as within a few days, despite the less advanced viral forensic technologies of two decades ago.
  • Even though Wuhan is the home base of virus hunters with world-leading expertise in tracking novel SARS-like viruses, investigators have either failed to collect or report key evidence that would be expected if Covid-19 emerged from the wildlife trade. For example, investigators have not determined that the earliest known cases had exposure to intermediate host animals before falling ill. No antibody evidence shows that animal traders in Wuhan are regularly exposed to SARS-like viruses, as would be expected in such situations.
  • With today’s technology, scientists can detect how respiratory viruses — including SARS, MERS and the flu — circulate in animals while making repeated attempts to jump across species. Thankfully, these variants usually fail to transmit well after crossing over to a new species and tend to die off after a small number of infections. In contrast, virologists and other scientists agree that SARS‑CoV‑2 required little to no adaptation to spread rapidly in humans and other animals. The virus appears to have succeeded in causing a pandemic upon its only detected jump into humans.

The pandemic could have been caused by any of hundreds of virus species, at any of tens of thousands of wildlife markets, in any of thousands of cities, and in any year. But it was a SARS-like coronavirus with a unique furin cleavage site that emerged in Wuhan, less than two years after scientists, sometimes working under inadequate biosafety conditions, proposed collecting and creating viruses of that same design.

While several natural spillover scenarios remain plausible, and we still don’t know enough about the full extent of virus research conducted at the Wuhan institute by Dr. Shi’s team and other researchers, a laboratory accident is the most parsimonious explanation of how the pandemic began.

Given what we now know, investigators should follow their strongest leads and subpoena all exchanges between the Wuhan scientists and their international partners, including unpublished research proposals, manuscripts, data and commercial orders. In particular, exchanges from 2018 and 2019 — the critical two years before the emergence of Covid-19 — are very likely to be illuminating (and require no cooperation from the Chinese government to acquire), yet they remain beyond the public’s view more than four years after the pandemic began.

Whether the pandemic started on a lab bench or in a market stall, it is undeniable that U.S. federal funding helped to build an unprecedented collection of SARS-like viruses at the Wuhan institute, as well as contributing to research that enhanced them. Advocates and funders of the institute’s research, including Dr. Fauci, should cooperate with the investigation to help identify and close the loopholes that allowed such dangerous work to occur. The world must not continue to bear the intolerable risks of research with the potential to cause pandemics.

A successful investigation of the pandemic’s root cause would have the power to break a decades-long scientific impasse on pathogen research safety, determining how governments will spend billions of dollars to prevent future pandemics. A credible investigation would also deter future acts of negligence and deceit by demonstrating that it is indeed possible to be held accountable for causing a viral pandemic. Last but not least, people of all nations need to see their leaders — and especially, their scientists — heading the charge to find out what caused this world-shaking event. Restoring public trust in science and government leadership requires it.

A thorough investigation by the U.S. government could unearth more evidence while spurring whistleblowers to find their courage and seek their moment of opportunity. It would also show the world that U.S. leaders and scientists are not afraid of what the truth behind the pandemic may be.

More on how the pandemic may have started

Where Did the Coronavirus Come From? What We Already Know Is Troubling.

Even if the coronavirus did not emerge from a lab, the groundwork for a potential disaster had been laid for years, and learning its lessons is essential to preventing others.

By Zeynep Tufekci

Why Does Bad Science on Covid’s Origin Get Hyped?

If the raccoon dog was a smoking gun, it fired blanks.

By David Wallace-Wells

A Plea for Making Virus Research Safer

A way forward for lab safety.

By Jesse Bloom

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Alina Chan (@ayjchan) is a molecular biologist at the Broad Institute of M.I.T. and Harvard, and a co-author of “Viral: The Search for the Origin of Covid-19.” She was a member of the Pathogens Project, which the Bulletin of the Atomic Scientists organized to generate new thinking on responsible, high-risk pathogen research.