Viral: The Search for the Origin of Covid-19

‘The true laboratory is the mind, where behind illusions we uncover the laws of truth.’

SIR JAGADISH CHANDRA BOSE

The authors of this book, Alina Chan, a scientist in the United States, and Matt Ridley, a science writer in the United Kingdom, have found ourselves inexorably drawn into the mystery of how the Covid-19 pandemic began. Over the past year, we have each pursued surprising revelations and rumours swirling around the origin of the virus. These took us deep into details of bats and SARS viruses in southern China, sick pangolins confiscated from smugglers, and cutting-edge gain-of-function virus research carried out in laboratories in Wuhan and elsewhere. In particular, Alina’s life has been forever changed after plunging into the question of the origin of SARS-CoV-2, the causative agent of Covid-19, in May 2020. Her social media has since been transformed into an open forum where prominent scientists and internet sleuths spar, publicly, on the topic.

In April 2020 Matt wrote an essay for the Wall Street Journal about the virus’s origin, headlined ‘The Bats Behind the Pandemic’, focused on the puzzling similarity of part of the SARS-CoV-2 genome to that of a virus from a pangolin – a small ant eater – while most of the genome resembled that of a bat virus. (A genome is the full genetic sequence of a creature.) He then read the preprint of a paper by Alina and two colleagues, Shing Hei Zhan and Ben Deverman, which came to the stark conclusion: ‘Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV.’ Noticing that Dr Zhan was an expert on genomic analysis and the other two were specialists in viral vector engineering at the elite Broad Institute of MIT and Harvard, Matt judged that this preprint – a scientific paper yet to be peer-reviewed for publication – was probably a careful and reputable study. It had come to an electrifying conclusion: the virus causing the pandemic was evolving more slowly than one newly arrived in the human species from another animal normally would. This implied it was already well adapted to human beings from the moment it was first detected in Wuhan in December 2019.

On 21 May 2020, Matt wrote to Gary Rosen, an editor at the Wall Street Journal, proposing an article to revisit the origin question, centred on the new paper: ‘There is one new paper in particular that has really thrown the issue back into the melting pot,’ he wrote. ‘A team of scientists finds that unlike SARS, this virus showed very little rapid adaptation/evolution in the early weeks of the epidemic, implying it was already settled into its final form. This implies that the source was almost certainly not via pangolins and probably not the wet market. It was more likely brought to the market by a person not an animal. So we don’t know where it came from and that implies the source is still out there. Bad news.’

The newspaper commissioned him to write the article, so he contacted Dr Zhan and sent him a series of questions to try to understand the implications of the work for the origin of the virus. Clearly, one of the ways that a virus could have become ‘well adapted for humans’, in the words of the paper’s title, was by having spent time in human cells or in a so-called humanised animal in the laboratory. Humanised animals, usually mice, have had their genomes altered to include a key human gene, in this case the entry receptor for certain SARS-related coronaviruses. At the time, a laboratory accident or leak still did not seem likely to Matt. He wrote to Dr Zhan: ‘I’d like to focus on the issue of the lack of an apparent adaptive period of rapid genetic substitution, and its implication that the virus had been circulating in human beings for longer than expected. (I am not focusing on the lab-leak possibility, though I will probably mention it among other possibilities.)’

He received a lengthy, detailed and fascinating reply from Dr Zhan’s co-author, Alina. To Matt’s surprise, Alina did not pour cold water on his growing suspicions that a laboratory leak could not be ruled out. Indeed, she alerted him to a low-key announcement that week from the Chinese authorities that no animals in the Huanan seafood market in Wuhan had tested positive. This was consistent with the findings she and her colleagues reported in their paper that ‘the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources’. On 29 May 2020, the Wall Street Journal published Matt’s essay under the headline ‘So Where Did This Virus Come From?’ The article began: ‘New research has deepened, rather than dispelled, the mystery surrounding the origin of the coronavirus responsible for Covid-19. Bats, wildlife markets, possibly pangolins and perhaps laboratories may all have played some role, but the simple story of an animal in a market infected by a bat that then infected several human beings no longer looks credible.’

Over the next several months, increasingly intrigued by the failure to turn up evidence of a chain of infections in a market, a village or anywhere else, Matt came to rely more and more on Alina’s advice and insight as he pursued the story of the virus’s origin. Eventually, he proposed that they join forces to write this book. By the time they finished writing it, because of the pandemic, they still had not met in person.

The importance of finding the origin of Covid-19

How the Covid-19 pandemic started may be the keenest mystery of our lifetime. The saga will forever punctuate the history of humanity. It has led to the deaths of millions of people, sickened hundreds of millions and dramatically changed the lives of almost every person on the planet. The impact of this invisible virus can also be measured in weddings and gatherings cancelled, jobs lost and businesses bankrupted, schools closed and parents balancing childcare and work, clinical visits missed and treatments put on hold, and innumerable people living more isolated lives than before. If we do not find out how this pandemic began, we are ill-equipped to know when, where and how the next pandemic may start.

In 2019, with more than seven billion human beings crowding the planet, crushed into dense cities, travelling frequently and far, the world was akin to a forest of dry tinder poised for a pandemic to ignite. Yet infectious diseases were in rapid retreat. The great killers of the past were under better control. Smallpox was extinct, polio endangered, typhoid rare, plague suppressed, malaria retreating, tuberculosis at a lower level than for most past centuries. Even AIDS, which emerged in the 1980s, was killing fewer people every year thanks to new treatments and public health interventions.

With each passing year the scientific tools and resources available for tracking and controlling outbreaks became ever more ingenious. A new pathogen could be detected, isolated and analysed with unprecedented speed and precision. Its genome could be sequenced, its structure elaborated and its weaknesses probed as never before. From time to time a new scare would threaten: SARS, MERS, Ebola, Zika. However, many imagined that infectious and deadly pandemics would, in the near future, be consigned to history. Few envisaged that a pandemic of Covid-19 proportions was about to begin.

There were experts who warned that this complacency was unwise, that a global pandemic, caused by Virus X, might – perhaps would – occur again. Pandemic preparedness plans and vaccine development and distribution infrastructure had to be updated. Some governments heeded this advice, focusing on the threat of a new strain of influenza, that shape-shifting menace which defied vaccine designers all too easily. The Gates Foundation and the Wellcome Trust set to work on the Coalition for Epidemic Preparedness Innovations. Surveillance of pandemic threats, by sampling wildlife for viruses with the potential to jump species, was ramped up. The United States Agency for International Development’s Predict programme was established for this purpose. New antiviral drugs were tested. But none of this was enough to prevent a pandemic, as we now know.

When news broke on the penultimate day of 2019 that a pneumonia of unknown cause was sending people to hospital in Wuhan, a city of eleven million people on the Yangtze river in central China, the strongest bet was that it would soon be brought under control as SARS had been seventeen years before. It was, after all, more than a century since a respiratory disease had caused a global pandemic on the scale of millions of infections and deaths. Initial reports in January were confident that the novel coronavirus was being caught directly from animals and, like many such ‘zoonoses’ at first, would therefore not be so easily transmitted from person to person.

Yet in the first two weeks of January 2020, evidence mounted that the virus was spreading rapidly. By 20 January, the Chinese government was compelled to notify the world that the virus could indeed transmit between humans. Videos of overwhelmed hospitals in Wuhan began to leak online. Over the next months, scientists started to understand that pre-symptomatic individuals could transmit the virus to other people, and that the virus could spread via the air. Research and public health experts have described the SARS-CoV-2 virus as one of the trickiest pathogens to combat because of these unique characteristics that dramatically reduce the efficacy of standard public health interventions.

Identifying the source of the virus was not the most urgent priority at first, but in due course its importance would loom large, not for assigning blame, but for preventing future outbreaks. If some animal population is out there, carrying a virus exquisitely adept at infecting people, it must be found before it can trigger another pandemic. If some human practice had encouraged the spread – the farming of wildlife for food, say, or the disturbance of some natural habitat – this practice must cease. Or, if some research experiment or fieldwork project had gone awry, lessons must be learned, and laboratory practices reviewed. Searching for the origin of Covid-19 could not and cannot be some idle pastime for a few curious scientists and internet sleuths; it is a vital task for the safety of humankind and demands a rigorous, credible and evidence-based investigation by experts worldwide.

In the last year and a half, the official search for the origin of the virus has yielded no smoking gun. Tens of thousands of animals, both wild and domesticated, have reportedly been sampled across China. None has tested positive for the virus. The joint study convened by the World Health Organization (WHO) and the Chinese government resulted in more questions and fierce debates on when and how the virus emerged in Wuhan. A nagging question grew ever more urgent: why Wuhan? Out of all of the cities of the world, how did Wuhan become the original epicentre of the pandemic?

One of the most tantalising pieces of the puzzle was a medical thesis unearthed in May 2020 by an anonymous Twitter user called the Seeker, a former science teacher in India. It was around this once obscure thesis that numerous sleuths, journalists and scientists began to coalesce to trace the origin of Covid-19. The thesis carefully chronicled the story of miners in Yunnan province who had sickened with a mysterious pneumonia after working in a bat-infested mine in 2012. In the years afterwards, scientists from top laboratories, including the Wuhan Institute of Virology (WIV), home of China’s most high-security virus laboratory, had repeatedly made the long journey to visit the mine to find the virus that could have infected the miners. By their accounts, they did not succeed, but in 2013 the WIV team did collect a virus that would later prove to be the closest genetic match to SARS-CoV-2. Perhaps a clue to the origin of Covid-19 lies in that distant mine in south-west China . . .