The Daily Telegraph - Saturday - The Telegraph Magazine
Where did Covid-19 really come from?
Matt Ridley and Alina Chan go in search of answers
Fingers have been pointed at bats, pangolins and a shuttered wet market, but the world still doesn’t know where the virus that has so far killed more than two million people originated. Could the Wuhan Institute of Virology, the site of groundbreaking, sometimes controversial research into coronaviruses, hold the answer?
The world knows by now the story of the coronavirus: this disease that has ripped around the world, killing two million people and counting, leaving a swathe of devastation in its wake. We are all but certain it came from China. Yet surprisingly, even now, nobody knows how the pandemic began.
We were told early on that it started in a Wuhan wet market, possibly via smuggled pangolins, which infected people. Those pangolins had probably caught SARS-COV-2 from horseshoe bats, which are the animals that naturally carry Sars-like viruses. This was the story initially – and many thundering articles were subsequently written on the risk posed by such wet markets, the destructive trade in illegal wildlife, and why this should be the moment to end it.
But what if the virus that causes Covid-19 jumped from animals into people in a different setting – inside a laboratory? Specifically one where bat viruses were being studied?
There have been rumours along these lines, right from the start. At first they seemed little more than the conspiracy theories of crackpots spending too much time on the internet – including borderline racism directed at China. But, as the months have worn on, that original theory – of the wet market and pangolins – has become more questionable. Scientists probing into the origins of SARS-COV-2 have uncovered anomaly after anomaly.
As a science writer who has written about viruses on and off for 35 years, and a post-doctoral researcher at a top institute, we initially had little doubt that this would prove to be a natural phenomenon. Mother Nature is a better genetic engineer than human beings will ever be, and the opportunities for viruses to infect human beings are legion, especially where the live-wildlife trade flourishes.
Yet now we are not so sure. Evidence for a natural spillover has not emerged. Nor has evidence for a laboratory accident. But details of the research done by a laboratory in Wuhan on closely related viruses, and of the secrecy surrounding it, have grown increasingly hard to dismiss.
Last month, the US State Department, under the Trump administration, released an explosive statement saying that it had ‘reason to believe that several researchers inside the Wuhan Institute of Virology became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both Covid-19 and common seasonal illnesses’. The institute is China’s foremost research centre for such diseases and holds a database of more than 20,000 pathogen samples from wild animals across the country, mostly bats and rodents. ‘For more than a year, the Chinese Communist
Party (CCP) has systematically prevented a transparent and thorough investigation of the Covid-19 pandemic’s origin, choosing instead to devote enormous resources to deceit and disinformation,’ it added. A team of World Health Organization investigators is currently in Wuhan, but on terms set by China’s government.
Crucially, the statement did not rule out the possibility that the virus may have escaped from the institute. ‘The virus could have emerged naturally from human contact with infected animals, spreading in a pattern consistent with a natural epidemic. Alternatively, a laboratory accident could resemble a natural outbreak if the initial exposure included only a few individuals and was compounded by asymptomatic infection,’ noted the statement, adding that Chinese researchers have studied animal coronaviruses in conditions that ‘increased the risk for accidental and potentially unwitting exposure’.
So where did Covid-19 come from?
In April 2012, six men who had been clearing bat droppings in a disused copper mine in Mojiang county, in Yunnan, a province in south-west China, fell ill and were hospitalised in Kunming, Yunnan’s capital. Three of the men would die. In June, Dr Zhong Nanshan, the famous physician who in 2003 figured out how to treat patients suffering from the first SARS virus – SARS-COV-1 – was consulted. He inferred that a similar virus might be responsible, and advised identifying the bat species in the mine, and testing the patients for SARS.
Doctors eventually deduced that Dr Zhong had been correct – behind the miners’ illness was a Sars-like coronavirus found in horseshoe bats. Tests were run, some by the Wuhan Institute of Virology (WIV), a thousand miles to the north-east.
This is where the virologist Dr Shi Zhengli works. For years she had conducted field expeditions to sample bats in caves elsewhere in Yunnan for viruses, as part of a long-term project to track down the sources of Sars-like viruses and measure the threat they posed. These expeditions brought the viruses back to Wuhan to be genetically sequenced and in some cases used in animal-infection experiments.
After the Mojiang miners fell ill, Dr Shi sent at least seven expeditions to the site to catch and sample bats. They brought back nine Sars-like coronaviruses. Other top Chinese labs also went to sample viruses from the Mojiang mine.
On 30 December 2019, Dr Shi was at a conference in Shanghai when she heard of an outbreak of infectious pneumonia in her home city of Wuhan. She rushed back on an overnight train. Later, she told Scientific American magazine that one of her early thoughts was, ‘Could [the coronaviruses suspected to be the culprit] have come from our lab?’
FOR SOME, IT WAS JUST TOO COINCIDENTAL THAT THE OUTBREAK BEGAN SO CLOSE TO THE WIV
She concluded not. This new disease had appeared in a seafood market selling exotic wildlife in Wuhan: of 41 cases of people with the disease, 27 had visited the market. Within a month of the Chinese Center for Disease Control and Prevention (CDC) announcing the origins of the virus being animals at the market, four different Chinese research groups reported that they had found a similar virus in smuggled pangolins confiscated in 2019 in Guangdong, a southern province, which was also where the 2003 SARS outbreak had started.
The source of the virus therefore seemed clear: pangolins, trafficked into Wuhan, were the culprits that had conveyed the newly named SARS-COV-2 from bats into humans. By all accounts, this was a rerun of the SARS epidemic, whose origins were traced back to animals called palm civets in markets, and ultimately to horseshoe bats. This was the story told to the world, and one that was, initially, almost universally accepted.
In February, however, a short article was released by two Wuhan scientists, Botao Xiao and Lei Xiao, pointing out that Wuhan laboratories had mounted expeditions across China to collect and study bat viruses. It made the bold statement that ‘in addition to origins of natural recombination and intermediate host, the killer coronavirus probably originated from a laboratory in Wuhan’. The paper was later withdrawn and some concluded it was an empty guess.
Nevertheless, when sequencing Wuhan’s novel coronavirus – determining the order of the genetic letters that make up its genome – Dr Shi found that it closely resembled a short sequence from a bat virus her lab had collected in the Mojiang mine back in 2013. In publishing this finding in Nature magazine in February 2020, however, Dr Shi made no reference to Mojiang or the miners, and gave the bat virus a different name – RATG13 – from the one used previously. Nor did she mention that her laboratory had sequenced and studied RATG13 as early as 2017.
This lack of transparency meant that it was left to a group of diligent online sleuths, including scientists in Innsbruck in Austria and Pune in India, a Russian-canadian biotech entrepreneur, an anonymous Twitter user known as ‘The Seeker’ and a group going by the name of DRASTIC, to fill the gaps. They found the original identity of RATG13, connected it to the Mojiang mine, located the site of the mine and unearthed a thesis from Kunming Medical University that revealed what had happened to the Mojiang miners.
These revelations were eventually confirmed by Dr Shi in November 2020, in an addendum to the earlier Nature paper. This also revealed that eight other Sars-like viruses had been collected from bats in the mine. Yet it gave no names or genetic data for these eight viruses. Moreover, WIV’S virus database had been taken offline – which Dr Shi told the BBC was for security reasons. As more tantalising details emerged, journalists from the BBC and Associated Press attempted to visit the Mojiang mine, but were tailed by police and stopped by impromptu roadblocks.
For some, it was just too coincidental that the outbreak of SARS-COV-2 had begun so close to the WIV, the foremost laboratory for studying such viruses in the world, which had collected large numbers of coronaviruses from a thousand miles away.
The lack of transparency surrounding the bat-virus projects is one reason that the public scientific consensus has been slowly shifting on the origin of the virus. Early in 2020, many scientists confidently ruled out the suggestion that it might have escaped from a lab. ‘We stand together to condemn conspiracy theories suggesting that Covid-19 does not have a natural origin,’ announced 27 prominent scientists in The Lancet on 19 February. ‘Our analyses clearly show that SARSCOV-2 is not a laboratory construct or a purposefully manipulated virus,’ proclaimed experts in Nature Medicine on 17 March.
Today, however, a growing number of experts (see box) agreed when we put it to them that a lab leak remains a plausible scientific hypothesis to be investigated, regardless of how likely or unlikely.
Another reason for this shift is that the market no longer looks like the site where the pandemic began. In May last year, the director of the Chinese CDC announced that none of the animal samples collected from the Wuhan wet market had tested positive for Covid-19. It was, he declared, ‘more like a victim. The novel coronavirus had existed long before.’
The statement followed months of speculation that the Wuhan wet market was not the site of the spillover from animal to human population. Independent analyses had already shown that some of the earliest patients had no links to the market. Nor did virus sequences from surfaces at the market point to cross-species spillover: they implied that the market cases were human-tohuman transmissions.
Moreover, the pangolin evidence now looks weak as well. As
one of us (Chan) discovered, all four studies of the pangolin virus most like SARS-COV-2 relied on the same data set from a single batch of pangolins intercepted in Guangdong in March 2019. There is no evidence of widespread infection among pangolins, let alone in Wuhan. As Dr Angela Rasmussen, of the Georgetown Center for Global Health Science and Security, put it, ‘The pangolin samples are a mess, and likely not relevant.’
A further surprise was in store. Chan and her colleague Dr Shing Hei Zhan scrutinised the evolutions of SARS-COV-1 (the cause of the 2003 SARS epidemic) and SARS-COV-2 (the cause of the current pandemic) in the early months of their respective outbreaks and found that while the former mutated rapidly in early human cases, as the virus adapted to its new host, the latter did not. This implies that the virus causing Covid-19 was already well adapted to infecting human beings, a point that was also suggested by the World Health Organization in its global study on the origins of Covid-19, published in November.
There are three possible explanations for this. The first is that the virus had circulated, undetected, in people for months. The second is that the virus was already highly adept at human-to-human transmission, even while it was still in bats or other animals. The third is that it had become adapted in human cells, or humanised animals, in a laboratory.
That such viruses circulated in humans in Wuhan seems unlikely. Dr Shi and her colleagues at the WIV have been sampling people, as well as bats, in rural Yunnan in the areas where Sars-like viruses are found in bats. By a stroke of good luck they used the population of their home city, Wuhan, as a comparison in one 2015 study: of hundreds of people tested in Wuhan, none had antibodies against Sars-like viruses.
Yet there is little doubt that the pandemic began in Wuhan. All the early cases were in the city and the majority of the first recorded cases in other countries were among people who had travelled from Wuhan. Persistent attempts by the Chinese government and scientists to play up possible origins in frozen-food imports and pre-wuhan cases in Europe have been unpersuasive so far.
There is still no sign of an original animal source of SARS-COV-2 in Wuhan, or the rest of Hubei province. Horseshoe bats that live in the area have been extensively sampled for viruses for years without SARS-COV-2-LIKE viruses showing up. Therefore, the strongest connection between such viruses in Yunnan and the human outbreak in Wuhan is the WIV, and the fact that it had collected Sarslike viruses from the Mojiang mine.
But this is circumstantial, not direct evidence. Although SARS leaked from a Beijing laboratory twice in 2004, infecting 11 people, there have been no public reports of an accident at the WIV. Moreover, RATG13 is not SARS-COV-2: there are significant differences between the viruses. This is why full transparency about all the viruses held in the WIV would be helpful, including all of the Sars-like viruses collected in the Mojiang mine.
We know from published work that Dr Shi and her colleagues were not only analysing the genomes of viruses, they were also manipulating them. This includes the creation of ‘chimera’ or hybrid viruses with genes taken from two different viruses. It also includes the testing of these viruses in ‘humanised’ mice, endowed with a certain human gene.
The practice of building chimera coronaviruses, sometimes leaving no trace of manipulation, is not new. Such experiments have been conducted in select laboratories such as the WIV for years, for the purpose of understanding how novel viruses could spill over into humans. The ultimate goal is to create a universal vaccine for all Sars-like viruses.
The scientists might find it unbearable if they instead caused a pandemic. But they did not find it unthinkable. In a 2015 article co-authored by Dr Shi these words appear: ‘Scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue… The potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens.’
Some time in 2019 in Wuhan a virus appeared that was already adept at infecting human beings and that was related to bat viruses from a long way away. Whether it arrived in the lungs of a traveller from a rural village in Yunnan, or through something that went wrong in a laboratory, we do not yet know. But tracking down its origins becomes more vital with every day that passes.
Matt Ridley’s book on the origin of the pandemic, Viral, will be published in 2021. Alina Chan is a postdoc at the Broad Institute of MIT and Harvard