The origins of the SARS-CoV-2 virus


Recently there has been an upsurge of interest into the origins of the SARS-CoV-2 virus, the one that causes covid-19, with speculation that it may not have originated by mutating spontaneously into a form that could transfer from animals to humans but that it may have been leaked from a research laboratory that does work on such viruses. Most proponents of the lab leak theory have suggested that the leak was accidental but a few have suggested a darker possibility of deliberate release.

I have been trying to make sense of the debate and found this article by Mara Hvistendahl to be helpful in sorting through the various claims. Hvistendahl had been in China when the avian flu virus broke out in 2013 and she had visited the lab of a prominent researcher and avian flu expert Chen Hualan who had been doing the so-called ‘gain of function’ research that is seen by some as an indicator that the covid-19 virus did not come about by accident.

That work involved tweaking pathogens in order to study how they might become more contagious, a type of study that is often lumped under the shorthand “gain of function.” Proponents of such experiments argued that a better understanding of how viruses are transmitted from one species to the next could help public health experts ward off natural outbreaks. Critics worried that instead of aiding in global health, her research could spark a pandemic.

(The broad label “gain of function” can apply to less risky research, but critics are concerned mainly with research that involves making pathogens more transmissible in a way that might pose a risk to humans.) Understanding that debate is key to grasping how and why the mainstream media has charted such an abrupt shift, from branding speculation about a lab leak a conspiracy theory to enthusiastically, and prematurely, embracing it.

She discussed Chen’s earlier work back in 2013 that had caused a stir.

Shortly before my trip, she and her colleagues had published a paper in Science detailing a massive gain-of-function experiment with guinea pigs. It had involved swapping gene segments from H5N1 with those from the H1N1 swine virus, then infecting guinea pigs with the hybrid viruses. Her team found that they could get the virus to leap from one animal to another by switching out a single gene. The guinea pigs stood in for humans.

Even as China was in the midst of an outbreak with a clearly natural origin, critics worried that risky research on pathogens could give rise to a worse one. But that was eight years ago, before the discourse on such research had geopolitical implications.

This gain of function research was controversial even then but the intense debate stayed within the scientific community. But no more. It is now a hot political topic.

UNTIL RECENTLY, the suggestion that a virus could leak from a lab had no correlation with one’s political beliefs. The first SARS virus leaked from labs several times — including at least twice from the National Institute of Virology in Beijing. A 1977 outbreak of H1N1 in the Soviet Union and China is believed to have been caused by Soviet scientists experimenting with a live virus in a lab. A number of leading American laboratories have had significant safety breaches as well, including at the CDC.

Before the pandemic, the scientific press regularly covered such risks. In a 2017 article on the opening of the Wuhan Institute of Virology, Nature raised concerns about biosafety. The notion of a lab leak was also floated by Science early in the Covid-19 pandemic in an article that also discussed a natural spillover.

BUT THE MOMENT of correction we’re now in is dangerous in its own way. There is still no direct evidence to support a lab leak, and many scientists with no stake in the outcome still say that a natural origin is more likely. Scientific consensus has not, in fact, shifted toward a lab origin. But some pundits with the risky combination of a lack of expertise and an agenda have argued that a lab leak caused the pandemic, case closed.

The most honest experts say simply that they don’t know. “We’re not taking an advocacy position on one scenario being more likely than another,” Bloom, the evolutionary biologist, said in a Q&A published by his institute. “As a scientist it’s important to clearly convey that there is scientific uncertainty — especially because this is a hot-button topic.”

In these days, it is becoming increasingly difficult to separate the scientific from the political on a wide range of issues.

Comments

  1. consciousness razor says

    Reasonable and measured, as usual. Don’t you know that you’re supposed to immediately land hard on one “side” or the other and defend it to the hilt?

    I’m not sure how some people might interpret what you said…. But I guess some think that the purity of science is somehow being tainted by “politics,” which is a bad thing. I think that’s just mistaken. No matter how this pandemic got started, this does raise totally legitimate political issues that shouldn’t have been confined to a small part of the scientific community in the first place. We should all have a say in this sort of thing, experts and non-experts alike, because the risks pertain to all of us.

    I think the value of gain of function research is pretty questionable, relative to the risks. We could start with that, and we can just decide that it’s not worth it. Simple as that. Some researchers may not like it (while others would), but that’s just too bad. Deference to experts really only applies to certain things and only to a limited extent even then, and I doubt arguments to that effect will be convincing to many ordinary folks. If that’s the only leg they have to stand on, I don’t think it will work out for them in the end. (I guess that’s also if politicians actually decide to do something … certainly a big “if,” but it may happen in at least some places.)

    Also, as I remember bringing up in another thread maybe a couple weeks ago, what some people are apparently considering with regard to “safety” or “security’ is very weirdly specific or narrowly-defined…. Some very basic questions: Why are these kinds of labs located in such densely populated urban areas? Who thought that was okay? There are no decent answers. It’s as if it never even occurred to those responsible to look at anything beyond the walls of the lab itself when evaluating safety. Then … why not? It’s been well understood for a very long time that outbreaks can spiral out of control very quickly in such circumstances. So just don’t do that sort of shit. How hard is that, for people who are supposed to know better?

  2. garnetstar says

    All of science is in danger of being politicized now. I’ll bet that the Wright brothers couldn’t get a plane off the ground without someone leaping on its political implications, and saying you shouldn’t believe your eyes.

    The thing is, we really don’t know anything more about the virus’ origins than we did a year ago. The likelihood of natural transmission vs. lab exposure is exactly the same as it was then: highly in favor of natural transmission.

    A human-engineered virus is still close to zero likelihood, pretty much ruled out by the genome analysis in Nature published back in March 2020. The only other thing that we’ve learned is that the WHO found COVID in about 100 of the swabs they took in the (now empty) Wuhan marketplace, mostly near the floor drains where the blood and guts of butchered animals were washed away. Therefore, that some animals in that market had COVID. A point in favor of natural transmission.

  3. garnetstar says

    cr@1, I understand that the argument for the placement of such labs is that they need a huge number of personnel to work there, and so to live in the vicinity. Also that the labs need a lot of infrastructure and transportation and modern computer and electrical, etc., facilities, so end up being built in larger-populated places.

    Don’t know if that is a good argument or not.

  4. bmiller says

    I can’t remember who posted it, but the Bulletin of Atomic Scientists, who are hardly a “right wing” group by any standard posted a very thorough look at the question. Their conclusion was less positive than yours’ garnetstar. The article seemed to be edging, carefully but still definitely edging towards, serious skepticism about the natural source theory. I am NOT a biologist so cannot claim any expertise, but the experts who wrote the article (popular press level essay, not scientific paper) had a more worrisome take on the question. And as far as politicizing the issue, they also pointed out that the United States was funding a good part of this research in China! So the whole Trumpian “China Virus” thing was very, very questionable no matter what the source.

  5. garnetstar says

    bmiller @4, I read that Bull. At. Scient. article, too, by Nicholas Wade. And the very thorough debunkings of it done by virologists. Basically, a case of a science journalist who didn’t bother to look into the research, and so posed a lot of questions as problems that were already solved.

    I don’t have the links to the debunking, but if you google the author’s name and debunking, the articles should pop up.

  6. says

    Can someone help me understand. I have read that the real issue is was this virus tweaked by scientists to be this virulent or was it naturally as virulent as it is.
    Because from my reading, I’ve read that nature is quite messy when they mutate a virus but when scientists do it it is quite clean and clear.

    IOW, a natural mutation would show up as having indications of intermediary adaptations that went nowhere but a scientifically designed collection of mutations would be more straightforward and would show up on analysis.

    And that every analysis so far has not been able to indicate that it was scientifically designed and instead these analysis have shown that it was sloppy and thus consistent with the way evolution would do it.

    Thus, this is a naturally occurring virus that we simply have not yet found the original animal. And whether it leaked from the lab is a bit irrelevant at that point.

    IOW, if it got into the lab for study from a wild find that they can no longer trace/prove then it may have or may not have leaked. And it may have or may not have leaked intentionally, which is a totally different issue. But so what. If it was natural, then it was destined to spread world wide at some point anyway.

    And it seemingly “chose” to spread world wide while Trump was president and thus could demonstrate even to the buffoons just how incompetent he was. (Admittedly not all of them) If not for this pandemic, he just might have been reelected.

    Thus, we need to thank this virus. Yes, millions will die due to this virus, but who here believes that Trump wasn’t heading for billions of deaths or more.

    Now part of me wants to insist this concluding paragraph is snark, but part of me feels this is a realistic assessment of the Trump presidency.

  7. Matt G says

    Some places to go for more detailed analysis:

    Larry Moran at his blog Sandwalk.

    Orac at Respectful Insolence. Some of his work appears at Science-Based Medicine (as David Gorski).

    Science Duuude at Medika. He talks a lot about the specific changes in sequence of the spike protein.

  8. jrkrideau says

    @ 4 bmiller

    The Bulletin of Atomic Scientists article was written by a journalist who seems to have decided that there was a lab leak. He presents no newer evidence than what we knew in Feb/March 2020.

    I do not think any scientists with a decent biological background are saying that a lab leak is impossible. They are just saying that it looks extremely unlikely for a number of reasons that I, as a non-biologist, am not qualified to evaluate.

    We have already seen two WHO delegations visit Wuhan, neither of which seem to think the “lab leak” scenario is likely. The Chinese could be suppressing evidence but the last delegation seems to have looked at a lot of materials and talked to a lot of people. The more information and people involved, the harder it is to maintain a lie.

    Matt G @ 7 suggests some excellent sources to check out.

    An excerpt from my post to another blog on Wade vs Orac:

    As to qualifications Wade is a journalist with (wiki) “a Bachelor of Arts degree in Natural Sciences from King’s College, Cambridge in 1964”.

    Gorski (Orac) is an MD & Ph.D with a university appointment, an active research program and a publication record in the “role of glutamate receptors in promoting the growth and metastasis of breast cancer”, whatever that means. It does suggest that his biological knowledge may be a bit more up-to-date and deeper than Mr Wade.

    It is interesting that the USA has been ramping up its hostility towards China just as this Wade article appears.

    @ 7 Matt G
    Thanks for the reference to Science Duude.

  9. Matt G says

    The virus’s Spike protein coding region acquired a 12-base insertion (out-of-frame, interestingly) which introduced the famous “polybasic cleavage site” you have probably heard about. This site allows Spike to be cut and the virus to more efficiently enter cells expressing the ACE2 receptor. The cleavage site is not optimal, and was out-of-frame as I mentioned, which suggests a natural origin. Of course it it could also have been engineered in this manner to make it *look* like it’s “natural,” but it’s impossible to tell. I don’t recall if that 12-base sequence has been identified in another virus.

  10. Matt G says

    My comment @9 wasn’t my final version; not sure how my edits got lost. The changes were fairly subtle so I won’t correct them.

  11. K.Swamy says

    Please have a look at this site. Short for Decentralized Radical Autonomous Search Team Investigating COVID-19 , it is an informal amalgam of experts and lay researchers from across the world who painstakingly pieced together various strands of data and information to understand how the 2019 SARS coronavirus (SARS-CoV-2) or the novel coronavirus , emerged and raced through the globe.
    https://drasticresearch.org/

    How Amateur Sleuths Broke the Wuhan Lab Story and Embarrassed the Media
    https://www.newsweek.com/exclusive-how-amateur-sleuths-broke-wuhan-lab-story-embarrassed-media-1596958

  12. KG says

    There is a whole range of distinct possibilities that are routinely mashed togather as the “lab leak theory” (better: “lab leak hypothesis”). The consensus of relevant experts (which doesn’t mean absolutely all of them agree) is that SARS-CoV-2 arose naturally, almost certainly in bats. It also seems very unlikely that it was deliberately leaked: there seems no conceivable rational motive for doing so, so it would have to be the act of a disturbed or psychopathic individual. But the fact that the pandemic started within a few kilometers of the Wuhan Institue of Virology (WIV), which is the primary centre for research on bat coronaviruses in China (only Hong Kong University comes anywhere close -- I did a Scopus search on “bat coronavirus China” which confirmed this) can’t be dismissed as irrelevant. Sure, it could be a coincidence, but it’s a material fact. The earliest known cases have no known link to the wet market, although that was likely a place where it spread. The outbreak could be the result of the WIV’s activities even without anyone knowing it. Researchers from WIV routinely visit bat caves in Yunnan (where a considerable proportion of the locals have antibodies to bat coronaviruses) to collect samples -- a process that involves handling the bats and their bodily fluids. They wear protective gear, but human error or faulty gear is always a possibility. A researcher could have been infected with SARS-CoV-2 -- possibly asymptomatically -- brought it back to Wuhan, and passed it on, without the virus ever entering the lab for study, and without anyone knowing about it at any stage. And then of course there’s the possibility that the virus did enter the lab for study, leaked accidentally, and this has been covered up. Yes, the more lab workers have been interviewed by outsiders, the more likely it is that any cover-up would have failed, but if a leak was known or suspected, we can imagine the pressure the staff would come under from the Chinese government to keep quiet (I wouldn’t trust any government to be open about such a disaster, but we know the Chinese government routinely lies on a huge scale).

    As was noted in Mara Hvistendahl’s article, leaks of dangerous pathogens from labs are by no means unknown. Here is a recent Guardian article on the need to review lab security. When I raised the issue of the pandemic starting near WIV in a thread on Pharyngula, a scornful response was that research on coronaviruses is carried out in lots of places that are not, as WIV is, level 4 biosecurity labs -- unlike ebola, for example. This was what prompted my Scopus search -- but also, I noted that the pandemic surely indicates that research on bat coronaviruses should only be carried out in the most secure facilities possible. Covid-19 has killed many, many more people than ebola.

  13. John Morales says

    KG:

    Covid-19 has killed many, many more people than ebola.

    Because of its mode of transmission, not because of lesser lethality or nastiness.
    Due to that, ebola never became pandemic.

    (BTW, if I had to choose, I’d choose Covid over Ebola, any day)

  14. KG says

    John Morales@13,
    Yes, of course. The people who have died from each are still equally dead.

  15. garnetstar says

    K.Swamy @11, I did read scientific literature on the studies that you mention, and the scientific consensus on those is also that they made a lot of unjustified or not-informed assumptions.

    I’m sorry I don’t have any links to that info, I just read it and didn’t mark it.

    Anyway, the whole thing seems to boil down to: 1) the virus was definitely not human-engineered, 2) natural transmission, including possibly the researchers catching it from gathering their research samples, is the most likely, 3) there were animals in the Wuhan market that definitely had COVID, and 4) accidental release from the lab is also possible, though less likely, and as yet there is no information or data that points to that.

  16. garnetstar says

    KG @16, sorry, once again, I read all that and didn’t mark it and forget where it was.

    It was mentioned in the interview with three of the WHO virologists who did the Phase I study in Wuhan, which is posted on Larry Moran’s site mentioned @7. They went on and on about how all the COVID they found was associated with the grates over the floor drains that the animals’ blood and guts were flushed down, but they couldn’t identify the specific animals because they’d all been disposed of long ago.

    Then, a lot of pieces and comments in Nature, published in the issue(s) right after the WHO report was published, whenever that was. I recall that that’s where scientists stated “There was definitely COVID in some animals in the market.”

    Sorry for being so vague!

  17. consciousness razor says

    garnetstar:

    It was mentioned in the interview with three of the WHO virologists who did the Phase I study in Wuhan, which is posted on Larry Moran’s site mentioned @7.

    One of those three is Peter Daszak, who is now recused from a current investigation/commission due to his conflicts of interest and for failing to declare his own ties to the WIV.

    (Also, he’s a zoologist, not a virologist. His wiki page also brands him as a “consultant and public expert on disease ecology,” but really his “job” is being the president of an NGO.)

    Newsweek article from last week:

    “The Wuhan Institute of Virology kept live bats in cages …. disproving denials from World Health Organization investigators who claimed the suggestion was a ‘conspiracy’.”

    Markson pointed towards one member of the World Health Organization team investigating the origin of the pandemic in Wuhan, Peter Daszak, and noted the zoologist said it was a conspiracy to suggest bats were held at the Wuhan Institute of Virology.

    “No BATS were sent to Wuhan lab for genetic analysis of viruses collected in the field. That’s now how this science works. We collect bat samples, send them to the lab. We RELEASE bats where we catch them!” Daszak tweeted in December of 2020.

    “This is a widely circulated conspiracy theory. This piece describes work I’m the lead on and labs I’ve collaborated with for 15 years. They DO NOT have live or dead bats in them. There is no evidence anywhere that this happened. It’s an error I hope will be corrected,” he tweeted again on December 10 of 2020.

    Markson told Carlson: “People like Peter Daszak insisted that it was a conspiracy theory – he used the term in a tweet from December 2020 – that it was a conspiracy theory to say that there were bats in the lab.

    “He’s an official WHO, World Health Organisation, investigator who went into Wuhan to supposedly investigate the origins of the virus earlier this year and it was completely false.

    “This new footage shows that there were bats being kept in the Wuhan Institute of Virology and it’s something Peter Daszak has had to admit, has had to correct just this month.”

    (Video and images at the link)

    It would be nice if we could have a source who’s more honest or more knowledgeable — preferably both.

  18. garnetstar says

    Well, there were the other two virologists on the WHO panel. One was Danish and one from the Netherlands. I don’t think they had conflicts of interest, or, none that have yet been disclosed.

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