Two years ago, in September and October 2019, something invisible happened in the city of Wuhan, China. A virus that caused a pneumonia-like illness began spreading, at first among a few people. Within months it exploded into a global pandemic that by now has directly killed 4.8 million people and indirectly perhaps twice that or more.
The pandemic strain, a coronavirus, carried a feature known as a furin cleavage site, located on the spike protein. When cleaved by furin, a human enzyme, this site enhances the ability of the attacking virus to enter human lung cells and produce disease.
We live in a sea of viruses. Why did this particular one break out in this huge Chinese metropolis, and not elsewhere? Where did the virus acquire the furin cleavage site, since no other viruses in the sarbecovirus subgenus, to which its closest relatives belong, have this feature?
The origin of the virus is unknown. A credible investigation is needed and could help prevent the next pandemic. Much more could be done to get at the truth, but it is not being done.
Coming up empty-handed
One major hypothesis is that the pandemic began with zoonotic spillover, a leap from animals to people, perhaps from bats to an intermediate host. The vast majority of human viruses have zoonotic origins. Bats harbor a large variety of viruses, and huge populations of bats roost in southeast Asia. One of the genetic sequences that is closest to SARS-CoV-2, known as RaTG13, with 96.2 percent genetic similarity, was found in 2013 in a bat cave in Yunnan province in southwestern China. Another three bat species, found recently in caves in northern Laos, yielded viruses with up to 96.8 percent similarity to the pandemic strain. Wildlife farming was quite widespread in China before the pandemic. Live, slaughtered and frozen wildlife was sold at the Huanan seafood market in Wuhan and many other markets in China. In December 2019, the Huanan market was linked to human cases, though it appears to have been an amplifier of the spreading virus, not the original source.
If zoonotic spillover in China triggered the pandemic, one might expect to find the pandemic strain in some of these places. But so far, researchers have not.
Recently, a group of scientists led by Zhiqiang Wu published the preliminary results of a study in which they cast a very wide net looking for the pandemic virus — or a progenitor closely related to it — among bats in China. They examined 703 sampling sites in urban, rural and wild areas across China where bats are suspected or confirmed to carry sarbecoviruses. Swabs from 13,064 bats were examined. They found plenty of samples related to the first SARS virus from 2002-2004. But “we did not find any” viruses related to SARS-CoV-2 in the samples, they said, indicating the pandemic virus “might not actively circulate among bats in China.” Similarly, in the joint China-World Health Organization report issued in March, it was reported that, in “sampling and testing of 38,515 livestock and poultry samples and 41,696 wild animal samples from 31 provinces in China from 2018 to 2020, “no positive samples were found” for SARS-CoV-2 antibodies or nucleic acid tests.
It is possible the pandemic strain acquired the furin cleavage site in the wild by genetic recombination, in which viruses exchange bits of genetic material. In the past, it has taken years or decades to discover the natural host for a new human disease outbreak. A simple explanation may be that more time is needed to trace the origins of the pandemic strain.
The virus found in Laos had similarities to the pandemic strain but lacked the furin cleavage site. If the pandemic strain came from bats in Laos or elsewhere in Southeast Asia, why did the outbreak start in Wuhan alone, and not anywhere else? If the pandemic strain isn’t found in China’s natural environs, then where did it come from?
Is China seeking answers? The leadership covered up the human transmissibility of the virus for the first three weeks of January 2020. Then the government advanced a propaganda campaign claiming the virus originated outside China, perhaps in the United States at the biodefense facility at Fort Detrick, Md. China is governed by an authoritarian party-state. Would a researcher dare to contradict the propaganda now?
No problem, no investigation
If not a direct zoonotic spillover, the virus could have hitchhiked a ride to Wuhan on a laboratory worker collecting samples in caves. The Wuhan Institute of Virology (WIV), one of the world’s major research centers on bat coronaviruses, gathered samples in a five-year collaboration with the New York-based nonprofit EcoHealth Alliance with funding from the National Institutes of Health (NIH), among others. The work involved teams from the Wuhan lab making repeated expeditions to bat cave sites in Yunnan province, about 1,000 miles southwest of Wuhan, from which they collected 16,000 samples.
Peter Ben Embarek, who led the joint China-WHO mission, told a Danish television interviewer that it is likely “a lab employee infected in the field while collecting samples in a bat cave” may have been at fault. But he said Chinese officials told him there was “no need to waste time on that.” The director of the WIV’s high-security virus research lab, Yuan Zhiming, assured the joint WHO mission that in all the thousands of virus samples handled there, “No infection was ever reported.”
A serious investigation must include examination of laboratory logs, reports of experiments and accidents, and personnel health records. Mr. Yuan, however, insisted that “annual external audits were conducted routinely. No problems had been identified.” This is hard to believe, especially in light of a January 2018 cable in which U.S. officials who visited the WIV described “a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.”
A third route
Wuhan is a major biological research center. The president of the EcoHealth Alliance, zoologist and parasitologist Peter Daszak, worked closely with bat coronavirus expert Shi Zhengli of the WIV. Their research pursued how bat coronaviruses might emerge from nature and become a danger to humans. Over time, their experiments became increasingly proactive, genetically modifying viruses to see what caused greater infectivity and transmissibility from bats to humans.
Details of this research are described in grant proposals by EcoHealth Alliance to the NIH, recently made public by the Intercept after a Freedom of Information Act lawsuit. The grants were funded over several years. The researchers were using another bat coronavirus, known as WIV1, which is related to the virus that caused the SARS epidemic of 2002-2004. They genetically manipulated it by installing spike proteins from three other related viruses, thereby creating three novel coronaviruses. These three could not have triggered the pandemic if they somehow escaped from the lab or infected a researcher, but they show that “gain of function” experiments — making organisms more infective — were ongoing in Wuhan. The chimeric viruses were then tested on mice with respiratory cells genetically altered to resemble those in human lungs. The NIH decided the experiments did not fall under U.S. restrictions on gain-of-function research, a decision that has drawn criticism that NIH oversight was lax.
In 2018, Mr. Daszak sought federal funding for even riskier gain-of-function research. He made a startling proposal to the Defense Advanced Research Projects Agency (DARPA), titled “Project DEFUSE,” which was recently disclosed by the research group DRASTIC, probing the laboratory leak hypothesis. Mr. Daszak proposed to identify and “defuse” emerging dangers in bat coronaviruses. One lab experiment he suggested would engineer a furin cleavage site onto the backbone of a coronavirus. This would enhance the virus to better infect human cells in the same way as the pandemic strain did. The WIV was a partner in the proposal, along with a lab at the University of North Carolina and others.
DARPA rejected Mr. Daszak’s proposal, saying it included potential gain-of-function research. Did the WIV go ahead with any such research on its own? Could it have replicated Mr. Daszak’s proposal? The answer isn’t known, but the WIV had years of experience working with Mr. Daszak and others. The WIV has never disclosed the full extent of its research. In September 2019, it took offline major databases of its virus samples, and never brought them back.
Is this how the virus appeared in Wuhan? Was there a laboratory accident or leak of some kind at the WIV? China has denied it. Mr. Daszak did not respond to our questions. He has been a vigorous advocate of the zoonotic spillover hypothesis, and has criticized those who raise the possibility of a laboratory leak. He organized a letter by 27 scientists to the Lancet, a British medical journal, in February 2020, insisting that scientists “overwhelmingly conclude that this coronavirus originated in wildlife.”
Understanding the origins of this pandemic could help prevent the next one. But without a thorough investigation, these questions will not be answered. So far, such a probe does not exist. The initial efforts, such as the joint China-WHO mission and the U.S. intelligence community report, raised more questions than they answered. No investigation will succeed as long as China’s doors remain shut.
The silence is deafening.