12.
Spillover
‘If it looks like a duck, and quacks like a duck, we have at least to consider the possibility that we have a small aquatic bird of the family Anatidae on our hands.’
DOUGLAS ADAMS
At the heart of this story lies a very simple fact. Somehow, an ancestral version of the SARS-CoV-2 virus came from a bat and ultimately infected people. That basic truth remains undeniable. Even if you think it was subject to genetic manipulation or some kind of human help along the way, this creature would still be fundamentally a product of evolution, a natural being, a wild organism. The majority of its genome is intact, original and natural, even if you put a question mark over a few small parts of it. It is one of many SARS-like viruses, and SARS-like viruses were invented by Mother Nature, not by people. So the theory that the pandemic began as a natural spillover was from the start, and remains to this day, highly plausible. It is the null hypothesis, the default assumption. It deserves its day in court. This chapter is the case for its defence.
The case begins something like this. Ladies and gentlemen of the jury, somewhere in a southern Chinese province, not necessarily in Mojiang County, there are horseshoe bats carrying viruses with genetic components reaching 98–99 per cent similarity to those in SARS-CoV-2. This must be true. The same has already been found for the 2003 SARS virus, and the scientists who discovered these bat coronaviruses concluded that recombination among these precursors resulted in the direct ancestor of the 2003 SARS virus. That we have not found these precursors for SARS-CoV-2 is hardly surprising. It is like searching for a needle in a haystack consisting of vast populations of bats ephemerally infected with viruses that are continuously recombining and evolving. The bat hunters described in this book have done a remarkable job in tracking down many sarbecoviruses in horseshoe bats, tying them to SARS, understanding how they are related to one another and how they evolve. Even a generation ago, little of this knowledge-building would have been possible. We would have been guessing where the virus came from, stumbling around in the scientific dark. It is the fact that we know so much and have at our fingertips so much greatly enhanced scientific capability this time around that enables us to be suspicious of gaps in knowledge and inaccessible evidence.
To blame those diligent virus hunters for the pandemic is like blaming a bystander or even a first responder for an accident. The main case against them is that they were present at the scene. But of course they were present at the scene! They were trying to help; they were trying to prevent a pandemic. They said it again and again. A pandemic caused by a novel SARS-like virus was always on the horizon. The very fact that they were there, sampling thousands of bats in caves all over southern China, is not proof they caused the pandemic, but it is part of the evidence that there was already a real threat of a natural pandemic. They warned repeatedly that bat viruses were ‘poised for emergence’, in the words of one of their papers. And emergence is what has happened. They are entitled to say, ‘I told you so.’
Next, remember SARS. It is a close cousin of SARS-CoV-2 and it emerged. It spilled over. We still do not quite understand how or where. Bats may have infected civets which infected people. Or they may have infected people who infected civets. But it is universally accepted that there was no helping hand from science – there was no SARS research lab in the middle of Guangdong; indeed, researchers had to traverse mountains and rivers in search of viruses carrying the ancestral building blocks of the 2003 SARS virus. And the pattern of early cases, with food handlers and chefs among the first to be infected, pointed to infection through the food chain. A significant portion of animal traders in Guangdong had antibodies against SARS virus despite not having been previously diagnosed, speaking to the frequent exposure of animal traders in the province to SARS-like viruses. If SARS virus could spill over naturally, so could SARS-CoV-2. SADS, the pig diarrhoea disease of 2016, is another example: a direct infection of pigs by bats.
Or take Ebola. As we were writing these words, Ebola broke out again in Guinea. Nobody was claiming that this is because bat virus-hunting scientists were doing risky experiments. It was because, as in 2014, a person has been exposed to bats in their natural environment. Ebola has emerged about two dozen times in the past forty-five years in central Africa. Each time it has been a natural spillover.
Or take MERS or Nipah or Hendra: new viruses that spilled over from bats within living memory. They needed no help from scientists in laboratories (Marburg virus is an exception). Why, in a world where this happens again and again, should we suddenly abandon this simplest of explanations for something more complicated and novel?
Then consider recombination. The SARS-CoV-2 virus appears to have the backbone of one virus but parts of the spike gene of another. Which is what we can expect of these coronaviruses. We knew before the pandemic that recombination was their thing, especially in and around the spike gene. The long search for the progenitor of SARS eventually concluded that all the parts of the SARS virus were present in R. sinicus bats in the Shitou cave, but not in one virus and not in one bat. It was a jigsaw of interchangeable parts, continuously switching in and out among closely related viruses.
Then there is the evidence of seroprevalence: around the bat-filled caves of Yunnan, a small percentage of people have antibodies to SARS. There is undoubtedly occasional natural spillover going on. If that’s true, why does the spillover of SARS-CoV-2 need to involve a scientist? True, it is a long way from Mojiang to Wuhan, but scientists were not the only ones making that journey. With bullet trains and freeways, rural people in China are on the move as never before. As the pandemic has shown us, a virus can and has travelled thousands of miles in an infected person. And a virus like SARS-CoV-2, which doesn’t manifest severe symptoms in the majority of its victims, is likely to have remained undetected until a superspreading event in a densely populated major transit hub such as Wuhan city.
Sure, nobody appears to have got infected along the way between southern China and Wuhan before the first cases were detected in Wuhan. But that is not impossible. Suppose again the index patient was an illegal wildlife smuggler heading to Wuhan as surreptitiously as possible, interacting with few people along the way, driving his truck at night and not yet very infectious. He might not give his virus to anybody along the way.
A sensible attorney is prepared to concede some things to the other side so as not to spoil the case by arguing implausible things. In this case we must concede that the frozen-product or cold-chain hypothesis is nonsense. It provides a fanciful possibility that the virus came from abroad, and it was unfortunately endorsed as more likely than a laboratory leak by the China-WHO team. In mitigation, as we saw, one of the team members, Dr Fabian Leendertz, said they agreed to include the frozen-food theory merely ‘to respect, a bit, the findings’ of Chinese scientists. It is just not possible to devise a version of that story that makes sense without seeing infections elsewhere, especially at the site where the frozen product was prepared for export. The ‘Popsicle Origins’ hypothesis just passes the buck, posing the question of how the virus got on the frozen food in the first place. Yes, frozen products might occasionally carry the virus from place to place during the pandemic, but there is no solid evidence that a person has ever caught SARS-CoV-2 from a frozen product and this hypothesis cannot explain the origin of the pandemic. Even the China-WHO team leader, Dr Peter Ben Embarek, conceded that ‘there were no widespread outbreaks of COVID-19 in food factories around the world’ back in 2019 and that imported goods were ‘not a possible route of introduction’.
Now comes the tricky part for the lawyer in court. We must explain away the peculiar behaviour of the Wuhan scientists, their apparent efforts to conceal the links between viruses in their collection and a mineshaft in Mojiang where three men met their deaths from a mysterious pneumonia. We must explain the refusal to divulge the sequences of the eight closely related SARS viruses from the mine more than a year after SARS-CoV-2 was first sequenced. Easy: the scientists were afraid of being blamed so they did what they could to prevent a narrative developing that would cast shade on them. In a secretive and autocratic system they were afraid to be open. Similarly, at the level of the local Wuhan government and even at the level of the Chinese government, censoring information and deflecting blame is to be expected – regardless of whether the virus emerged naturally or via a laboratory leak. This had already been demonstrated in the first SARS outbreak of 2003. You may not like the lack of transparency, and we don’t, but it is hardly proof of guilt. In some ways, they have been remarkably open. ‘Could they have come from our lab?’ was Dr Shi Zhengli’s first thought when she heard about the first novel coronavirus cases in Wuhan. Would she really have said that if she was trying to cover up a link to her lab?
The lawyer also calls expert witnesses to the stand. Prominent virologists have argued that SARS-CoV-2 is the seventh coronavirus known to infect humans – nothing unnatural about it. The virus is also known to infect a wide range of species and bind effectively to the ACE2 protein in different host species. It can thus be termed a ‘generalist’ virus, not one that is specifically optimised for human beings alone – although humans are near the top of its list. Furthermore, there is a simple reason to doubt that this virus was engineered in a laboratory. SARS-CoV-2’s genomic sequence does not match any known virus reported by any laboratory around the world. The closest virus genome, RaTG13, is only a 96 per cent match – too distant to be used as a template. There are also no reports of novel SARS-like viruses being serially passaged in human cell culture or in humanised animals. The mechanism by which the spike protein’s receptor-binding domain attaches to the human ACE2 receptor depends on certain amino acids in the sequence. A team of genetic engineers would surely have borrowed a known recipe. Yet, despite all the Chinese research theses being unearthed by sleuths, none have revealed any sequences that could point to a SARS-CoV-2 precursor being studied in a laboratory before the 2019 outbreak. Until actual evidence surfaces to show that a SARS-CoV-2 precursor was in the possession of scientists before the outbreak, the onus is on those who argue for laboratory origins to substantiate their speculations.
In addition, since the emergence of SARS-CoV-2, a growing number of its close relatives have been discovered in Southeast Asia and even Japan, within a broad range of Rhinolophus bat species, suggesting that these viruses are widespread. The most probable origin scenario is that SARS-CoV-2 evolved naturally, either in an animal host population (likely a species sharing a similar ACE2 with human beings) before spillover into humans, or in a remote human population before detection in Wuhan in late 2019. Consider that many of the early cases of Covid-19 were linked to a market in Wuhan so it remains possible that an animal at the market transmitted the virus into people. The belated publication in the middle of 2021 of a paper describing the sale in Wuhan markets of all sorts of live mammals must to some extent increase the possibility of an animal in the market serving as the intermediate host of SARS-CoV-2. Although no animals or animal samples from Wuhan markets or elsewhere in China have been found to be the original source of the virus, it is possible that wildlife vendors might have quickly hidden their infected animals upon hearing news of the outbreak. Remember that the Huanan seafood market was thoroughly disinfected in such a hurry that the animal source might have been missed or even destroyed in the process. It remains entirely possible that the animal source will be found as Chinese scientists continue to test more farms and animal populations.
Wuhan’s Huanan seafood market before its closure on 31 December 2019.
Imaginechina Limited/Alamy Stock Photo
Ladies and gentlemen of the jury, the attorney goes on, you will hear from the other side that the furin cleavage site is deeply suspicious and puts scientists right at the scene of the crime. But why? Lots of coronaviruses have such a feature naturally. True, none of the sarbecoviruses have one, but so what? It could easily emerge by recombination, mutation or a mixture of the two. That specific region of the spike is prone to mutation. Viruses related to SARS-CoV-2 have been revealed to have possible insertions where the SARS-CoV-2 furin cleavage site is located; these could be intermediates to a functional furin cleavage site. There is a real example of such a site appearing as if by magic in an experiment involving a bovine coronavirus: it was already there as a rare variant and selection in the laboratory brought it to the fore. Something similar may have happened in the case of SARS-CoV-2 but in nature rather than inside a lab.
Then there is the lack of direct evidence of a laboratory leak. Where is the infected laboratory worker, the index case? Where is the record of an accident? If there was a leak, why, in the months since the pandemic began, has no scientist come forward with a confession or an eyewitness account? The Chinese regime may be authoritarian, but it is not omnipotent. The lack of a whistleblower with genuine evidence of an escape of the virus into the community must count for something.
Do not forget that there is no evidence at all that the SARS-CoV-2 virus was the subject of experiments in any laboratory. The WIV had published scores of papers on the various viruses it had manipulated and tested in its laboratories. Never once in this flood of papers did it mention a virus that could be a precursor to SARS-CoV-2. If the jury is to believe that such work was nonetheless happening, it would have to conclude that the pandemic began during a relatively brief window in which experiments had taken place but nothing had been submitted for publication.
Finally, there is the motivation of those pursuing the laboratory-leak hypothesis. Many of them have been passionate opponents of experiments on viruses with pandemic potential – some even since before the gain-of-function moratorium of 2014. They are bound to think that this is what they have been warning against. Others are in the arms control business and have devoted their lives to warning against the dangers of bioweapons. This pandemic is a godsend to such people and their budgets, so they are bound to recruit it to their cause. Others are fervent opponents of genetic engineering and this episode fits their world view. Others still are critics of the Chinese Communist Party and will readily believe any theory that blames the Chinese state. Still others, especially in journalism, are motivated by sensationalism. They want this to be a big story and a human-made leak is a much bigger story than a bat that shat on a passer-by. Finally, there are some who simply succumb to the all too human tendency to think that where there is pain there must be blame. The intentional stance, philosophers call it: the tendency to infer intention into even random events. If we think half seriously (and we sometimes do) that even the weather is vindictive when it chooses to rain on the day of a wedding, how much easier is it to think that a pandemic must be human-made? These witnesses are not dispassionate and sceptical assessors of the evidence but ready believers in whatever version of a laboratory origin scenario best fits their prejudices. In the fine old human tradition of confirmation bias, to which anyone is susceptible, they will seek out the evidence that is compatible with their theory and ignore what does not fit.
In conclusion, ladies and gentlemen of the jury, says the attorney, there is no evidence of a laboratory leak, and the default assumption must remain that this pandemic began with a natural event, as so many other epidemics have done in the past.