Wednesday, February 02, 2022

The COVID-19 Virus Probably Leaked from Shi Zhengli's Lab in Wuhan: Should We Blame Francis Bacon?

                                     A Transmission Electron Micrograph of SARS-CoV-2 Viruses

It has killed almost six million people over the past two years, and it continues to kill more every day.  It has made hundreds of millions of people sick, some severely so.  It has disrupted the life of almost every person on the planet.  The evolution of the SARS-CoV-2 virus (SARS2) that has caused the COVID-19 pandemic has had--and will continue to have--a major effect on the evolutionary history of life on the Earth.  This evolutionary change will continue as the virus evolves, along with the coevolution of the human physiological and behavioral immune systems.   And yet, amazingly, we are still not sure exactly where, when, or how the SARS2 virus originated. 

There is growing evidence, however, that SARS2 emerged and was perhaps created in virologist Shi Zhengli's laboratory at the Wuhan Institute of Virology, with research funding from the U.S. government, and that the pandemic began in Wuhan when the virus accidently leaked out of her laboratory.  

I have changed my mind about this.  In the spring and summer of 2020, I suggested--in posts here and here--that the virus probably evolved naturally in bats before it passed into humans (perhaps through an intermediate animal).  But then beginning in May of last year--in posts here and here--I argued that there was plenty of evidence for the virus having evolved artificially in Shi's lab and then accidently leaking out of her lab into Wuhan, when some of her lab workers became infected.

If this is true, it should provoke lots of questions about who we should blame and how we might prevent this from happening again.  But the deepest question, I have suggested, is whether we should blame Francis Bacon and the modern scientific project that he initiated, because Shi's governmentally funded research looks like the sort of publicly sponsored scientific research carried out in Salomon's House in Bacon's New Atlantis.  Bacon promised that modern science and technology could master nature "for the relief of the human estate."  Shi and her colleagues have justified their research with the same promise.  They have promised that their research would allow us to predict and prepare for new infectious viruses, so that we could avoid future pandemics and produce new vaccines to give us immunity to dangerous viruses.  But now it seems likely that this research produced not a vaccine but a plague.  

Should we conclude from this that our support for modern science and technology has been a Faustian bargain with the Devil?  Or should we say that this is a good bargain--as long as we understand that regulating scientific research to avoid unnecessary risks is part of the bargain?

We now have a new book to help us think about these questions--Alina Chan and Matt Ridley's Viral: The Search for the Origin of Covid-19 (New York: HarperCollins, 2021).  In the debate between those who believe the Covid-19 pandemic began with a natural spillover of the SARS2 virus from animals (originally horseshoe bats in southern China) and those who believe it began with an accidental leak of that virus from a lab in Wuhan, Chan and Ridley concede that there is no demonstrative proof for either side.  But as of now, they argue, the greater weight of the evidence is on the side of the accidental lab leak theory.

To support that conclusion, they engage in what the medieval scholastic philosophers would have identified as "disputation."  They imagine opposing attorneys summarizing their arguments before a jury.  In chapters 12 and 13 of their book, Chan and Ridley present the attorney for the natural spillover theory followed by the attorney for the lab leak theory--with the first attorney making 12 arguments and the second making 10 arguments.  I will briefly state those arguments here.


(1)  What we know about the evolution of the 2003 SARS virus indicates that it almost certainly originated through a natural spillover from horseshoe bats to humans.  Shi Zhengli and her colleagues identified the bat coronaviruses that were the precursors of the SARS virus that infected human beings.  These same scientists have argued that the SARS2 virus probably originated in the same way--as a natural spillover from bat coronaviruses.  And although they have not yet found the direct ancestor of the SARS2 virus, they have found bat coronaviruses that are remarkably similar to SARS2.  That should be enough to convince us that the Covid-19 pandemic probably originated from a natural spillover.

(2)  The primary reason that some people believe that the SARS2 virus leaked out of Shi's lab in Wuhan is that the first people infected with the virus were in Wuhan; and the researchers in Shi's lab had been sampling and studying bat coronaviruses from southern China for many years.  But the proximity of the Wuhan lab to the first identified infections is only a coincidence.  We should assume that someone was infected with the virus somewhere in southern China and then the virus was passed to people in Wuhan.

(3)  This natural spillover of infectious viruses to humans from bats has occurred many times--not just with the SARS virus but also the Ebola, MERS, Nipah, and Hendra viruses.  We should assume that SARS2 fits into the same evolutionary pattern.

(4)  The SARS2 virus appears to be the product of recombination: combining parts from many different viruses.  That happens all the time with viruses--they evolve by switching genetic parts in and out of closely related viruses.  We can assume that SARS2 emerged naturally from that evolutionary process of viral recombination.

(5)  It is true that for many years Shi and her colleagues have been visiting bat caves in the southern province of Yunnan, and therefore there could have been a spillover from a bat to the scientists.  But a small proportion of people in Yunnan have antibodies to SARS, which indicates occasional natural spillovers.  We can easily imagine that someone became infected with SARS2 and then travelled north through China until the virus reached Wuhan.

(6)  In February of last year, a team of investigators from China and the World Health Organization held a press conference at which they proposed that the SARS2 virus could have been transmitted to Wuhan on some frozen food.  This has been ridiculed as the "Popsicle Theory."  And scientists have generally rejected it as implausible.  But a good lawyer defending the natural spillover theory could rightly concede this without weakening his case.

(7)  From the beginning of the Covid-19 pandemic, Shi and her colleagues have been remarkably secretive about their research, as if they were concealing evidence that might support the lab leak theory.  For example, on February 3, 2020, Nature published the first paper on the SARS2 virus by Shi and her colleagues, which reported that they had found in the Wuhan lab's collection a bat coronavirus called RaTG13 that was a 96.2 percent genome match to SARS2.  They did not report, however, that this RaTG13 strain had been collected in 2012 from patients who had become sick in Yunnan Province after visiting a mine cave to clean bat feces in order to mine copper.  Nor did they report that between 2012 and 2015, they had collected from the same cave eight other betacoronaviruses that were SARS-related, and that in 2018 they had obtained almost the full-length genome sequence of RaTG13.  They finally reported all of this on December 3, 2020, in an Addendum to their February Nature article.  Why did they keep all of this secret for almost a year?  Well, their defense lawyer might argue, they were afraid of being blamed for the pandemic, and so they hid any information that might be interpreted as suggesting a lab leak of the Covid virus.  But even if we can rightly criticize their lack of openness, this is no proof of their guilt.

(8)  The SARS2 genomic sequence does not match any known virus reported anywhere prior to the identification of SARS2 in January of 2020.  Even the RaTG13 virus genome is only a 96 percent match, which is still not close enough to be a direct precursor of SARS2.  Proving the lab leak theory would require evidence that scientists had a SARS2 precursor in their labs before the pandemic began.  Until such evidence appears, the lab leak theory is only an unsubstantiated speculation. 

(9)  Many of the early cases of Covid were linked to an animal market in Wuhan.  We now know that although there were no bats or pangolins in that market, other kinds of live mammals were sold there.  A transmission of the virus from these animals to humans is a serious possibility.  Although no animals have been found to have the SARS2 virus, it is possible that wildlife vendors quickly hid their infected animals when they heard about the outbreak.

(10)  One primary reason why the SARS2 virus so easily infects human beings is that it has a furin cleavage site.  Furin is an important protein in human cells, because it cleaves proteins in two so that they can change shape to better perform their functions.  Furin is attracted to the right place in each protein by special sequences of amino acids.  The furin cleavage site in SARS2 has a genetic recipe for four amino acids in a key spot of the spike gene of the virus, which attracts the furin protein to cut the spike protein in just the right way so that it forces the fusion of the virus to a human cell and allows the virus genome to enter the cell.  Other coronaviruses that infect humans attract furin, but they are not in the subgenus of SARS-like (sarbecovirus) viruses.  SARS2 is the only sarbecovirus with a furin cleavage site.  Virologists can experimentally insert furin cleavage sites in the spike genes of coronaviruses.  And so proponents of the lab leak theory have argued that the furin cleavage site in SARS2 must be the product of a lab experiment.  But the lawyer for the natural spillover theory could argue that the furin cleavage site could easily have emerged by recombination or mutation in this part of the spike gene.

(11)  Perhaps the best argument against the lab leak theory is that there is no direct evidence for it.  No one has identified an infected laboratory worker.  No one has reported a laboratory accident in Wuhan.  Even if the Chinese government has tried to suppress any evidence for a lab leak, it's hard to believe that this explains why there has been no whistleblower.

(12)  Finally, we should notice that the proponents of the lab leak theory are personally motivated to do this, because many of them are opponents of genetic engineering and of experiments with virus that might have some risks.  Moreover, there is a natural human resistance to believing that a global catastrophe like a pandemic can arise from random events in nature.  When we suffer from a plague, we want to blame someone; and in the tradition of the Frankenstein story, many of us want to blame the mad scientist.


Now let's hear the response from the attorney for Chan and Ridley.  This attorney would begin by making it clear that he is not trying to argue that the scientists in Wuhan intentionally created the pandemic.  They were not designing a bioweapon.  Their intention was good: they wanted to study potentially dangerous viruses so that they could predict pandemics and find ways to avoid them.  If there was a lab leak, it was accidental.  A scientist was accidentally infected with the SARS2 virus either through contact with bats in the wild or in the laboratory, and then this infection was transmitted to others in Wuhan.

(1)  The first point to make is that lab leaks do occur.  Alison Young, a journalist who has tracked lab leaks in the United States for the past 15 years, has written about this in USA Today ("Could an Accident Have Caused Covid-19?," March 22, 2021).  Around the world, in even the most secure labs, there have been accidental releases of SARS, anthrax, smallpox, foot-and-mouth, Marburg virus, and other pathogens.  Luckily, there has been no clearly identified case of a major pandemic caused by a lab leak.  There is only one possible case of a pandemic that began in a lab, although there is disagreement about it among the scientists who have studied it.  In 1977, an Influenza A (H1N1) strain of flu swept over the world, beginning in China.  This strain of flu was genetically identical to an H1NI flu that had been common in the 1950s but then disappeared.  One theory about this is that in some lab somewhere, this flu strain from the 1950s had been thawed out to develop new vaccines, and that the live attenuated virus used as a vaccine recovered its ability to cause the disease.  There's a dispute, however, as to whether this should count as a lab leak (see Chan and Ridley, 148-51).  In any case, as long as lab leaks occur, causing a pandemic is possible.

(2)  Consider also that although it has been over two years since the SARS2 virus was identified, there is still no direct evidence for its natural origin.  By contrast, in the case of the SARS epidemic in 2003, it was quickly determined that the first people who were infected were food handlers.  Scientists visited a live animal market in Shenzhen, Guandong, in southern China.  The SARS virus was isolated from five of the animals.  They also found that some of the animal handlers had antibodies to SARS.  The highest antibody prevalence was found in those who primarily traded civets.  No evidence like this has been found for SARS2.  None of the animals from the Huanan seafood market in Wuhan tested positive for SARS2.  Thousands of animals across China have been tested, and there is no sign of the SARS2 virus in any of them.

(3)  Unlike the SARS virus of 2003, which was seen to evolve during the early months of the outbreak to become better adapted for infecting humans, the SARS2 virus was well adapted for infecting humans from the start of the outbreak.  We have to wonder whether the SARS2 virus had developed its remarkable ability for infecting and transmitting among humans through evolving in a laboratory.

(4)  Why have the Chinese authorities and the scientists at the Wuhan Institute of Virology (WIV) refused to release the two kinds of data that could refute the lab leak theory?  The WHO investigators have not been permitted to see the hospital records of the early Covid-19 cases or the information about the locations and professions of the first people infected.  If this showed no connection to any laboratory in Wuhan, this would be evidence against the lab leak theory.  Another important kind of data is the WIV's database of fifteen thousand bat samples from southern China.  That database could be found online until it was taken offline in 2019 on September 12 between 2 a.m. and 3 a. m.  Why?  What's the point of building such a database over many years and then not allowing anyone to see it?

(5)  Another big question is: why Wuhan?  Is it just a coincidence that the SARS2 virus emerged first in the one city in the world with the largest collection of bat sarbecoviruses and the most active lab studying these viruses?  Isn't it odd that this city is over 620 miles from the region of China where SARS-like viruses are found naturally?

(6)  It was almost a full year after the beginning of the pandemic before the WIV revealed that it had a collection of SARS-like viruses collected in an abandoned copper mine in Mojiang with many bats, where workers had been sickened with a SARS-like illness in 2012.  This collection had nine viruses very genetically similar to the SARS2 virus.  Why the delay?

(7)  International journalists trying to visit that Mojiang mine have been blocked by police and by people guarding the entrance to the mine.  Why?  Shouldn't this create some suspicion that the SARS2 virus might have originated there, and that the WIV scientists taking samples from the bats there might have taken the virus back to their lab in Wuhan?

(8)   Some of the best evidence that laboratory scientists were probably responsible, even if unintentionally, for the pandemic is the record of their research.  Here's how Chan and Ridley describe that research:

"They did not just bring viruses from caves and mines in southern China to the laboratory for storage; they sequenced their genomes, made infectious clones of them, rescured live viruses from culture, passaged them through a range of laboratory-made cell lines of different animal species and cell types, synthesized and altered their genomes to insert specific sequences, hybridized genomes to combine parts of one virus's spike gene with backbones from another virus, and used these viruses to infect human respiratory tract cells and humanized mice genetically engineered to have human ACE2 in them.  This type of research carries a risk of, unintentionally, generating a more virulent or infectious version of a virus or selecting for bat viruses that are efficient at infecting human tissues and humanized animals" (287).

Moreover, we now know that Peter Daszak of the EcoHealth Alliance in collaboration with Shi Zhengli and others submitted a grant proposal in March of 2018 to the U.S. Defense Department's Defense Advanced Research Projects Agency (DARPA).  A leaked copy of this proposal was published a few months ago by The Intercept.  They proposed to insert cleavage sites into engineered SARS-like viruses: "We will analyze all SARSr-CoV S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential furin cleavage sites . . . we will introduce appropriate human-specific cleavage sites and evaluate growth potential in Vero [monkey kidney] cells and HAE [human airway epithelial] cultures."  The proposal was rejected.  One of the criticisms coming from a DARPA program manager was that the proposal "did not mention or assess potential risks of Gain of Function (GoF) research and DURC [Dual Use Research of Concern]."

Although this grant proposal was unsuccessful, we know that Daszak and Shi have had other sources of funding that they could have used.  We also know that scientists often write proposals to support research that they have already undertaken, and so it is likely that Daszak and Shi have been inserting furin cleavage sites into SARS-like viruses, which could have created the SARS2 virus.

(9)  Another argument for the lab leak theory is that many of the scientists who rejected the lab leak idea in the spring of 2020 had changed their minds by the spring of 2021 as the evidence for a lab leak piled up.  The critical turning point was a letter signed by eighteen scientists published in Science in the middle of May 2021, which said that the lab leak idea needed to be taken seriously.  For example, Bernard Roizman, a virologist at the University of Chicago, had rejected the lab leak theory in February of 2020.  But in May of 2021, he said: "I'm convinced that what happened is that the virus was brought to a lab, they started to work with it . . . and some sloppy individual brought it out . . . they can't admit they did something so stupid."

(10)  Moreover, we now know that the first reaction of many scientists early in February of 2020 was that the SARS2 virus must have been leaked from a lab, but that this should not be said in public for fear of promoting distrust of scientists.  Some Republican congressmen have recently forced the release of emails exchanged between scientists after a conference call on February 1, 2020, that show that these scientists were privately worrying about a lab leak even though they publicly denied this.  Ridley has written about this on his blog.

Jeremy Farrar organized the call on February 1 with Patrick Vallance, Francis Collins, Anthony Fauci, and a group of virologists.  In the emails after the call, many of the participants indicated that they thought a lab leak was the most likely source of the SARS2 virus.  But then a few days later, many of these people signed their names to public statements and articles rejecting the lab leak theory.  None of them has explained why they changed their minds, but their emails suggest that they thought publicly stating the truth would be too dangerous for science.


In those emails, Ron Fouchier warned that taking seriously the lab-leak theory would "do unnecessary harm to science in general and science in China in particular."  Similarly, Francis Collins warned about "doing great potential harm to science and international harmony."  Anthony Fauci said: "I would not do anything about this right now.  It is a shiny object that will go away in time."

If it were to become generally accepted that the Covid-19 pandemic was caused by a leak from the Wuhan lab, would that force us to reassess the whole Baconian project of modern science and technology?  In Bacon's New Atlantis, the scientific laboratories in Salomon's House are regulated by the scientists themselves, who decide what should be made public and what should be kept secret.  Can scientists be trusted to regulate themselves in deciding whether the likely benefits of their research outweigh the likely risks?  Or should ordinary citizens and politicians demand regulatory restrictions on what the scientists can do?

Even if we end up blaming Bacon's science for causing the Covid-19 pandemic, we must remember that Bacon's science also created the Covid-19 vaccines that have saved millions of lives.  Amazingly, the biotech firm Moderna completed the design of its experimental messenger-RNA (mRNA) vaccine to fight the SARS2 virus by January 13, 2020, only a few days after the sequencing of the SARS2 genome was made public!

We should also notice that Bacon's science seems to be close to developing a new universal coronavirus vaccine that could prevent future SARS-like coronavirus pandemics.  Ralph Baric and his colleagues have developed and tested such a vaccine in mice.  They started with mRNA--like the Moderna and Pfizer vaccines used today--but instead of including the mRNA code for only one virus, they created a hybrid or chimeric mRNA from multiple coronaviruses.  When presented to mice, this chimeric vaccine generates antibodies against multiple spike proteins, which viruses use to enter healthy cells.  This vaccine has the potential to be effective against every variant of the virus (David Martinez et al., "Chimeric Spike mRNA Vaccines Protect against Sarbecovirus Challenge in Mice," Science 373 [2021]: 991-998).

Even as we restrict Bacon's scientists to reduce the risks from accidental laboratory leaks that could cause another pandemic, we need to promote that research of Bacon's scientists that is likely to lead to new vaccines and therapies that protect us from dangerous pathogens. 

1 comment:

Kent Guida said...

I was just about to write and ask you for your current assessment of the Covid story. Then I opened the site, and voila. Great stuff. It's not Baconian science, it's the governance of Solomon's House. So far, the governors have managed to avoid all accountability. Will that last forever?