In 1977, an outbreak of H1N1 influenza began in the Soviet Union. It spread rapidly through schools and military camps, particularly afflicting those under 25, before becoming a global pandemic which lasted two years, reaching the UK, and eventually the US.
In total, it is thought to have killed around 700,000 people around the globe.
But when virologists began to study the so-called ‘Russian flu’, they noticed something highly unusual about the virus’ genetic sequence. It looked almost identical to a strain which had last been seen in the 1950s.
“Viruses evolve very, very quickly,” says Joel Wertheim, an associate professor of medicine at the University of California San Diego, who has studied the Russian flu outbreak. “If you gave me a flu virus, I could, within a pretty narrow range, tell you what year it came from, and the strain which began circulating in 1977 looks exactly like one in 1950. Now, there’s no place in nature for influenza to hide out and not mutate, the only place where it doesn’t mutate is the freezer.”
To Wertheim and others, it was pretty obvious that the 1977 outbreak had not originated in the wild.
In 2004, the virologist Peter Palese wrote that a member of the Chinese Academy of Sciences had told him that the reintroduction of H1N1 was thought to be the result of vaccine challenge trials involving several thousand military recruits.
Although the origins of the pandemic are still unknown, the World Health Organisation (WHO) has rejected the idea that H1N1 was a product of a laboratory accident.
Still, lab accidents do happen. The virus which caused the original SARS outbreak in 2003, has since escaped from virology labs on six separate occasions, in Singapore, Taiwan and Beijing.
Over the past year, Wertheim’s work on the Russian flu has been the subject of renewed interest. While the initial scientific consensus was that the COVID-19 pandemic had a natural origin, speculation has grown over the past year regarding whether the Sars-CoV-2 virus could possibly have escaped from the Wuhan Institute of Virology, a lab which was studying nine of its closest viral relatives at the time.
These questions have been fuelled by China’s reluctance to fully cooperate with outside investigators, even those from the WHO, and share critical information. In an editorial for the journal Nature, members of the WHO team investigating the origin of the pandemic warned that time is running out to conduct tests that might help identify how COVID-19 began. Reports have also continued to emerge which detail odd behaviour from Wuhan scientists, both before, and in the earliest stages of the pandemic.
In September 2019, the Wuhan lab abruptly took a database of more than 22,000 pathogen samples offline. Then in early 2020, it first uploaded, and then subsequently deleted, 13 genome sequences from a US government database. These sequences were from some of the earliest cases of COVID-19 to have been detected in Wuhan.
“I think it’s suspicious,” says Alina Chan, a researcher at the Broad Institute of MIT and Harvard University, who has been one of the most vocal voices calling for the need to investigate the possibility of a lab leak. “They did not put it anywhere else, and refused to respond to comments. So if it had been taken down for an innocuous reason, why wouldn’t they respond to people who reached out and said, ‘What did you do with the data?’”
Chan’s own scientific detective work has provided increasing traction to the theory that COVID-19 might have had a non-natural origin.
It claimed that SARS-CoV-2 was unusually well placed to invade the human body when it first came to attention in December 2019.
Investigations of what had been taking place at the Wuhan lab over the past decade have only continued to stoke the fire.
There have been reports that scientists at the institute were conducting controversial and high-risk ‘gain-of-function’ experiments which attempt to modify a natural virus to make it more infectious or virulent, in order to give virologists a head-start on tackling dangerous pathogens of the future.
However, all of this is still nowhere near enough proof that the COVID-19 pandemic began with SARS-CoV-2 escaping from the Wuhan institute. To begin with, there is still no evidence that the virus ever passed through the lab, and not all scientists agree that early samples of the virus display particularly unusual characteristics.
“This virus was not exceptionally adapted to humans upon arrival,” says Wertheim.
“This was not some perfectly adapted strain, this was a virus that has got a lot better at infecting humans and transmitting between humans since it arrived. We know this because we’ve seen it adapt since early on, and the rise of further variants in the past year.”
For scientists to be really convinced that the pandemic was started by a lab leak, Wertheim says there would need to be concrete evidence that the Wuhan lab had been holding a virus which matched the genetic sequence of Sars-CoV-2 partially or in full, or epidemiological data connecting some of the earliest transmission clusters to the institute.
But proving the opposite theory – that Sars-CoV-2 spilled over from the wild – is just as hard. Both the Sars and Mers outbreaks, caused by similar coronaviruses, were traced back to intermediary animal hosts – palm civets in the case of SARS, and dromedary camels in the case of Mers – which were in close contact with humans, helping the virus cross the animal-human barrier. However, while tens of thousands of animals have been tested over the past eighteen months, the search for the intermediary host of SARS-CoV-2 has been an elusive one so far.
Again, evidence has emerged that China has hindered efforts on this front.
While data given to the WHO from the Chinese government suggested that only snakes, crocodiles and salamanders were being sold live in Wuhan’s wet markets, a new paper published last month revealed that in reality, 38 different species – from civet cats to raccoon dogs – were being sold between May 2017 and November 2019.
“Those animals were never disclosed to the WHO in their investigation,” says Wertheim. “So there was never the opportunity to test the most relevant animals.”
Chan believes that one of the reasons why crucial information has been withheld is because China is trying to push its own narrative of how the pandemic began.
“China has its own preferred origin scenarios,” she says.
“These involve either the virus emerging from frozen meat, or emerging in multiple countries at the same time. Neither one of these is either scientifically plausible I think, but it does move the blame outside of China.”
But while such political sensitivities have obscured the quest to solve the mystery of how COVID-19 began, scientists have made some progress when it comes to determining when exactly the pandemic started. Knowing this time frame is crucial to pinpointing where and how the virus emerged in humans, whether from animals or the Wuhan lab.
Last month, one scientist managed to reconstruct the 13 genome sequences which were deleted by the Wuhan lab early on in the pandemic, after discovering that the removed files were still stored in Google Cloud.
His analysis – which has not been released in a peer-reviewed journal – provided evidence to suggest that COVID-19 actually began in October or even earlier.
“I wouldn’t be surprised if we get more data which pushes it back a few months before that,” says Sergei Pond, a biology professor at Temple University in Pennsylvania who has also been studying some of the earliest Sars-CoV-2 genetic sequences.
“And that’s always true for every epidemic, because by the time we realise that something’s wrong, it’s been going on for several months.”
But there is a limit to how much such forensic analysis can tell us. If we are ever to truly understand the origins of COVID-19, some major new revelations would be required. Because China is unlikely to cooperate with the rest of the world anytime soon when it comes to vital data-sharing, some scientists have already accepted that it is likely to be a mystery that is never solved.
“My personal view is that we will not have a full consensus on the origin of it all,” says Pond. “You’re going to have people that continue to insist that it was a lab release, but you can’t prove that definitively without eyewitness testimony or documentation, and it’s hard to imagine that even existing, let alone getting into the public domain. So I think we just have to continue with the assumption that this is a spillover from the wild.”
However, Chan believes that if China is hiding some dark secrets about how COVID-19 began, they will ultimately come to light in years to come, once the immediate crisis has subsided, and it becomes safer for any potential whistle-blowers to talk.
“At the moment, anyone who knows any secret information will be too worried to speak,” she says.
“But when time passes, it becomes safer for people to come and say something about what actually happened.”