So was COVID-19 made in a lab in Wuhan by 'mad' scientists?

Donald Trump is concerned, the conspiracy theorists say it's true — but here, we offer the science

The conspiracy theory that COVID-19 resulted from a virus produced and then mistakenly — or deliberately — released by a secretive biosecurity lab in Wuhan seems to have successfully infiltrated the brain cells of many, including those at the helm of the White House.

Mad scientist

It has even replicated a little like the virus itself, infecting its hosts with ideas retrofitted to known facts, yet ideas leaving them floundering from reality in a mass of half truths.

But the theory's rapid spread does explain the sudden immune response — the rush of commentaries published by virologists around the world who have come to recognise a pressing political need to make their scepticism public.

Why the virus is novel

An article in Nature Medicine, published as news emerged of an US investigation into the conspiracy claims, serves as one of just many examples.

Co-authored by Professor Edward Holmes, an evolutionary biologist at the University of Sydney, it starts by pointing out that SARS-CoV-2, the virus now responsible for more than 190,000 deaths, has two distinctive features.

The first is its so-called ‘receptor binding domain’ (RBD), the part of its protein spike which holds onto the wall of the host cell it is preparing to invade.

The vulnerability of humans seems to come partly from the make-up of this RBD, which has proved to be extremely effective at binding to the receptor ACE-2, the main entry point used by a variety of coronaviruses for entry into the cells of the lungs, arteries, heart, kidney and intestines.

The second feature of SAR-CoV-2 is its ‘polybasic cleavage site’. Made up of amino acids, this site attracts the human enzyme furin to cut and activate the spike protein necessary to unlock the host cell.

It is the exploitation of furin, found in so many tissue types, which could explain why the virus is so infectious, compared to other coronaviruses, such as MERS-CoV and SARS-CoV-1.

And it could also explain, given furin is expressed in significant concentrations in the lungs, why the virus proliferates from the lower respiratory tract to wreak its harms.

According to Professor Holmes, the challenge for scientists planning to engineer the virus in the lab is that these features are not obvious.

Intelligent design vs natural selection

Professor Holmes says the computer simulations used to predict the interactions between SARS-CoV-2 and ACE2 receptors would have suggested the binding would not work so well — or in his words, would not be “ideal”.

As a result, no genetic engineer making their own virus would have thought the approach was worth pursuing.

The reasons the RBD of SARS-CoV-2 turned out to be so effective in its job is simply that it evolved through natural selection, he says.

It was the success or failure, the do-or-die approach of nature, which resulted in its clever solution that would have been beyond the capacity of genetic engineers relying on intelligent design.

“Nature usually is better at doing things than we can figure out with a computer,” said letter co-author Dr Robert Garry, an assistant professor of microbiology and immunology at Tulane University School of Medicine in New Orleans, US.

“That's pretty good evidence that this virus did evolve to bind to human ACE2 on its own. Nobody helped it. If somebody had designed it, they would have used a different solution.”

No borrowed backbone

There is another, similar, argument against the Chinese lab theory.

Scientists are, generally, as savvy — or possibly as lazy — as the rest of us. They tend to build on current know-how. Asked to design a new car engine, the efficient approach is to adapt what already exists.

So, when the decision is made to create a new disease entity, surely scientists would opt to use the backbone of an existing virus — say, one of the several reverse-genetic systems available for betacoronaviruses — rather than spending months or years building a new system from scratch.

Yet this did not happen, according to Professor Holmes.

When the genome of SARS-CoV-2 was sequenced and released by the Chinese in January this year, he says, there was no evidence of human tinkering, no evidence that someone had taken a backbone from another virus to make it.

This is where the alternative explanations for what happened come in. Their attraction is that they are more basic and, at least for their proponents, more plausible or "parsimonious" as Professor Holmes would put it.

SARS-CoV-2 was the result of natural selection in an animal host before zoonotic transfer, or the result of natural selection in humans following zoonotic transfer.

Like many other coronaviruses, SARS-CoV-2 has close similarities to bat viruses.

Professor Holmes says this is unsurprising, given that bats are an important reservoir for a diverse range of coronaviruses.

But he stresses the exact role bats have played in the COVID-19 pandemic has yet to be established.

Yes, there is a bat virus named RaTG13 which, he says, is the closest known relative of SARS-CoV-2 — about 96% similar at the nucleotide sequence level.

And this virus, as the conspiracy theorists are keen to point out, was kept at the P4 Wuhan Institute of Virology.

But, Professor Holmes says, the genetic divergence between the two is equivalent to at least 20 years of evolutionary change.

“[And a] key issue is whether these [bat] viruses … contain the key RBD mutations and the same furin-like cleavage site insertion as found in SARS-CoV-2,” he wrote in a paper published in Cell last week.

The RaTG13 virus shares just one of the six critical amino acid residues making up the SARS-CoV-2 receptor binding domains.

Wider sampling of other bat viruses is still needed, he says, and the results may change views and reveal viruses even closer to SARS-CoV-2.

A pangolin. Source: iStock.

Source: iStock.


Scaly anteaters

But in the meantime, given the gaps in knowledge, there is that other animal suspect which may help explain the virus’s zoonotic origins.

The Malayan pangolin has been illegally imported into southern China and makes appearances at the wet markets.

It turns out that betacoronavirus obtained from the animal has not one but all six of those key mutations believed to shape binding to the ACE2 receptor.

The problem is that the polybasic cleavage sites are missing.

This is why some scientists have argued that the progenitor of SARS-CoV-2 may have infected humans and from there, through the process of (undetected) human-to-human transmission, acquired its distinctive features for cutting open the host cell.

Professor Holmes says: “While our past experience with coronaviruses suggests that evolution in animal hosts … is needed to explain the emergence of SARS-CoV-2 in humans, it cannot be excluded that the virus acquired some of its key mutations during a period of ‘cryptic’ spread in humans prior to its first detection in December 2019.”

It is possible that the virus emerged earlier in human populations than many envisaged — and perhaps not even in Wuhan, he argues.

It might not have been picked up sooner because asymptomatic infections, mild respiratory symptoms and sporadic cases of pneumonia were “not visible to the standard systems used for surveillance and pathogen identification”.

“During this period of cryptic transmission, the virus could have gradually acquired the key mutations, perhaps including the RBD and furin cleavage site insertions, that enabled it to adapt fully to humans.”

Lab-based cultivation?

What about nurtured, rather than natural, selection — what about the idea of growing and selecting versions of the virus in cell culture or maybe in animal models?

Maybe there was a security breach at the Wuhan lab and the resulting virus escaped.

In 2004, for instance, Chinese public health officials had to deal with an outbreak of SARS from a research lab in Beijing after two researchers — a 26-year-old female postgraduate student and a 31-year-old male postdoctoral student — were infected with SARS-CoV-1 in two separate incidents.

Around 200 staff were placed in quarantine as a result.

Professor Holmes says it is possible that SARS-CoV-2 acquired RBD mutations during adaptation to passage in cell culture. That basic research has been going on with bat SARS-CoV-like viruses from some years in biosafety level two labs around the world.

And new polybasic cleavage sites have also been produced in the lab, albeit after prolonged passage of low pathogencity avian influenza virus in vitro or in vivo.

However, it would be remarkable, or maybe better to say statistically unlikely, that a human process of forced selection in the lab managed to produce a virus with almost identical RBD features found in the viruses from Malayan pangolins.

Professor Holmes also stresses that the generation of SARS-CoV-2 in cell culture or animal passage would require securing a progenitor virus with a very high genetic similarity.

The argument here is that such a virus, at least within the wider scientific community, has not been described.

But it’s the generation of the virus’s defence against the human immune system — known as the glycan shield — that makes the petri dish/lab argument implausible.

Professor Nigel McMillan, director of infectious disease and immunology at Griffith University, on the Gold Coast, says: “In order to force their selection in a lab, you would need an active immune system. 

"No such lab-based system exists that can do this — you would need a live animal host."

Again, he says it’s possible, in theory, to generate the polybasic cleavage sites and the particular RBD mutations — and then put a virus with those properties into animals and hope something comes out the other end.

“But it would be very time-consuming, laborious, to create a virus suited to avoid the test animal's immune system and not that of humans, and so the likelihood of success would be very low.

“This, along with other genetic evidence, suggests on the balance of probabilities that SARS-CoV-2 is unlikely to be man-made,” he concludes.

Shaving with Occam's razor

Maybe none of these arguments will ever be persuasive to a conspiracy theorist, in part because as Professor Holmes makes clear, there are still factual gaps yet to be filled.

And in part because science only deals with statements that can, as a matter of principle, be proved false; as Karl Popper observed, by necessity they remain contingent no matter how good the evidence. 

But it is also because the arguments are grounded in what conspiracy theorists struggle with most of all — the idea that, faced with a choice of conflicting explanations, the simplest is most likely to be the best of them.

The current, still limited explanations for the origins of SARS-CoV-2 do have consequences, but the consequences are not condemnation of China and its ‘evil scientists’ for releasing a virus into the world that has caused such global harm.

They are a little more mundane, a little less explosive.

“Critically, the surveillance of animal coronaviruses should include animals other than bats, as the role of intermediate hosts is likely of major importance, providing a more direct pathway for the virus to emerge in humans,” Professor Holmes and Professor Yong-Zhen Khang, from China’s Fudan University, wrote in their Cell paper.

“Given the enormous diversity of viruses in wildlife and their ongoing evolution, arguably the simplest and most cost-effective way to reduce the risk of future outbreaks is to limit our exposure to animal pathogens as much as possible.”

They conclude: “While our intimate relationship with the animal world means we cannot build impregnable barriers, stronger action against the illegal wildlife trade and removing all mammalian (and perhaps avian) wildlife from wet markets will provide an important buffer.”


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Current Australian coronavirus statistics - 24 April

Total: 6667 confirmed cases, including 76 deaths:

  • 104 in ACT
  • 2982 in NSW
  • 27 in NT
  • 1026 in Queensland
  • 438 in SA
  • 207 in Tasmania
  • 1337 in Victoria
  • 546 in WA

Source: Department of Health, Coronavirus health alert