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Have you ever wondered if people read Master’s (or even Ph.D) theses a decade out? Whether or not you have, I think you will be intrigued to learn the story of why an obscure Master’s thesis from 2012, translated from Chinese in 2020, is now an integral key for unravelling the puzzle of the global controversy about the mechanism and origins of Covid-19. The Master’s thesis by a doctor, Li Xu [1], “The Analysis of 6 Patients with Severe Pneumonia Caused by Unknown Viruses”, describes 6 patients he helped to treat after they entered a hospital in 2012, one after the other, suffering from an atypical pneumonia from cleaning up after bats in an abandoned copper mine in China. Given the keen interest in finding the origin of the 2002–2003 severe acute respiratory syndrome (SARS) outbreak, Li wrote: “This makes the research of the bats in the mine where the six miners worked and later suffered from severe pneumonia caused by unknown virus a significant research topic”. He and the other doctors treating the mine cleaners hypothesized that their diseases were caused by a SARS-like coronavirus from having been in close proximity to the bats in the mine.

Jonathan Latham and Allison Wilson, scientists at the Bioscience Resource Project in Ithaca, decided Li Xu’s master’s thesis was important enough to translate from Chinese.

The evidence it contains has led us to reconsider everything we thought we knew about the origins of the COVID-19 pandemic. It has also led us to theorise a plausible route by which an apparently isolated disease outbreak in a mine in 2012 led to a global pandemic in 2019. (Latham & Wilson 2020)

They dubbed it the Mojiang Miner’s theory, because the mineshaft is located in Mojiang, in Yunnan province, China, 1000 miles from Wuhan. One of the mine cleaners from 2012, they speculate, might even have been patient zero of the current pandemic! But except for a brief sketch in note 5, I put that aside for this post and turn to the article that first sparked my interest in the Mojiang mine from the Times of London July 4, 2020. Its subtitle is: ‘The world’s closest known relative to the Covid-19 virus was found in 2013 by Chinese scientists in an abandoned mine where it was linked to deaths caused by a coronavirus-type respiratory illness’. For a long time, it was one of the only articles on the mysteries that came to light with this Master’s thesis: now the mine mysteries are mentioned in every critical discussion of Covid-19 origins.

I will likely write updates to this post (following with (i), (ii), etc in the title), and possibly follow-up posts. I started it weeks ago, and as I learned more, I decided it was too much for one post. Please share corrections in the comments.

1. The Mojiang Mine

The Times authors set the scene in their picturesque opening:

In the monsoon season of August 2012 a small team of scientists travelled to southwest China to investigate a new and mysteriously lethal illness. After driving through terraced tea plantations, they reached their destination: an abandoned copper mine where — in white hazmat suits and respirator masks — they ventured into the darkness. Instantly, they were struck by the stench. Overhead, bats roosted. Underfoot, rats and shrews scurried through thick layers of their droppings. It was a breeding ground for mutated micro-organisms and pathogens deadly to human beings. There was a reason to take extra care. Weeks earlier, six men who had entered the mine had been struck down by an illness that caused an uncontrollable pneumonia. Three of them died.

Today [back in July 2020], as deaths from the Covid-19 pandemic exceed half a million and economies totter, the bats’ repellent lair has taken on global significance.

Evidence seen by The Sunday Times suggests that a virus found in its depths — part of a faecal sample that was frozen and sent to a Chinese laboratory for analysis and storage — is the closest known match to the virus that causes Covid-19. (London Times)

The lab to which the sample was sent was the Wuhan Institute of Virology (WIV), home of a world renown site for bat coronavirus research, led by Shi Zhengli, often called “batwoman” in recognition of her years of bat coronavirus research.

The pneumonia the miners were suffering from was deemed sufficiently serious and unusual to immediately call in an acclaimed virologist, Professor Zhong Nanshan, who had led China’s efforts against the first SARS, referred to now as SARS-CoV-1 to distinguish it from SARS-CoV-2, the virus that causes Covid-19.

The Wuhan Institute of Virology (WIV) …was called in to test the four survivors. These produced a remarkable finding: while none had tested positive for Sars, all four had antibodies against another, unknown Sars-like coronavirus. (London Times)

The detailed description of their symptoms and disease progression in the Master’s thesis exactly echoes what we now see in those with Covid-19: high fevers, coughs, difficulty in breathing, and many of the treatments tried are also in sync with those used today, including one found to be one of the most successful: steroids.

Shi Zhengli was in the midst of researching bat caves around 200 miles from the Mojiang mine when her team was alerted to the miners. Given their main research focus is SARS-related coronaviruses, especially from bats, this was clearly of great interest to them. So they immediately turned to investigate the Mojiang Mine.

Over the next year, the scientists took faecal samples from 276 bats. The samples were stored at minus 80C in a special solution and dispatched to the Wuhan institute, where molecular studies and analysis were conducted. (London Times)

One, from a horshoe bat was of special interest because it was considered a brand new strain of a SARS-related virus. In a February 2016 article that Shi co-authored, the bat sample was named RaBtCoV/4991. Oddly, the paper, titled “Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft,” makes no mention of the reason the whole study took place: no mention of the miners or the fact that three died from pneumonia contracted from bats in the mine where the sample was found (Mystery #1). But what really raised an alarm for me is the fact that Shi, when asked about the miners (in an interview in the March-April 2020 issue of Scientific American, hereafter SA 2020) averred the miners were killed by a fungus and not a virus (Mystery #2).

Shi describes the mine as “a flying factory for new viruses” due to finding that often “multiple viral strains had infected a single animal.” While claiming it was a fungus that killed the minors, “she says it would have been only a matter of time before they caught the coronaviruses if the mine had not been promptly shut” (SA 2020). [I was struck to hear she thought they’d be directly infected, since from day 1 there’s often been an assumption that an intermediate species was needed.]

2. December 30, 2019 and the current pandemic

All that was pre-SARS-CoV-2. Away at a conference, Shi receives a call on Dec 30, 2019 that there’s a new coronavirus running rampant in Wuhan. Shi recalls the WIV director saying: “Drop whatever you are doing and deal with it now.” Her first thought as she makes her way back to Wuhan is ‘If coronaviruses were the culprit, she remembers thinking, ‘Could they have come from our lab?’”(SA 2020)

Her musing that the new virus might have come from her lab is, in one sense, unsurprising, given Wuhan contains three labs specializing in the study of bat coronaviruses, hers being the only one at biosafety level 4.

Shi breathed a sigh of relief when the results came back: none of the sequences matched those of the viruses her team had sampled from bat caves. ‘That really took a load off my mind,’ she says. ‘I had not slept a wink for days.’ …The genomic sequence of the virus, eventually named SARS-CoV-2, was 96 percent identical to that of a coronavirus the researchers had identified in horseshoe bats in Yunnan. Their results appeared in a paper published online on February 3 2020 in Nature.”

They dubbed it batcoronavirus RaTG13. In this 2020 article, co-authored by Shi, they write:

RaTG13 is the closest relative of [SARS-CoV-2] … The close phylogenetic relationship to RaTG13 provides evidence that [SARS-CoV-2] may have originated in bats.…On the basis of these findings, we propose that the disease could be transmitted by airborne transmission, although we cannot rule out other possible routes of transmission. (Zhou, Yang,…Shi, Nature 2020 article)

But wait, let’s go back. Why a sigh of relief that SARS-CoV-2 is only 96% identical to one of the bat samples? What about the numerous specimens taken from the Mojiang miners? How close are they to SARS-CoV-2? Frustratingly, to this day we’re never told. (Mystery #3) Moreover, while RaTG13 is described as being found in a cave in Yunnan, there is no mention of BtCoV/4991. Nor is there a citation of the initial 2016 article describing BtCoV/4991, even though it was co-authored by Shi (Mystery #4).

It turns out that RaBtCoV/4991 is identical to RaTG13! However, it required independent groups to sleuth this out [2]. (Mystery #5).

In fact, researchers in India and Austria have compared the partial genome of the mine sample that was published in the 2016 paper and found it is a 100% match with the same sequence for RaTG13. The same partial sequence for the mine sample is a 98.7% match with the Covid-19 virus. (London Times)

Why would the 2020 paper describing the closest relative to SARS-CoV-2 fail to mention that it is one and the same as the virus unearthed from the mine where 3 people died, and had already been cited in the 2016 paper, both with Shi as co-author? It’s one thing to rename it, but to fail to note this goes against typical publishing norms.

My initial attitude to the whole business of the origins of Covid-19 is that we’d probably never find out and anyway, the most important thing was trying to find treatments, prophylactics and vaccines, to understand the mechanism of Covid-19 and especially to prevent future pandemics. But it became clear that those goals hinge on the information that mysteriously was being hidden by the research groups being funded (by the U.S.) precisely to provide surveillance and monitoring about pandemics. Without being able to pinpoint all the individuals involved, I will just allude to the WIV research group from the time of the Mojiang Miners. (See also note 3.)

So what did the WIV research group do with RaBtCoV/4991 in the ensuing years between finding it in 2013 (2016 article) and the revelation in the early pandemic (2020 article)? According to them, not much: it was said to have been stowed away in a freezer and only taken out after cases of Covid-19 appeared in Wuhan at the end of December 2019.

Other scientists find the initial indifference about a new strain of the coronavirus hard to understand. Nikolai Petrovsky, professor of medicine at Flinders University in Adelaide, South Australia, said it was “simply not credible” that the WIV would have failed to carry out any further analysis on RaBtCoV/4991, especially as it had been linked to the deaths of three miners.

‘If you really thought you had a novel virus that had caused an outbreak that killed humans then there is nothing you wouldn’t do — given that was their whole reason for being [there] — to get to the bottom of that, even if that meant exhausting the sample and then going back to get more,’ he said. (London Times)

So it seems the WIV research group failed at “their whole reason for being” there, since the sample simply sat in a freezer for 6 years. Maybe if they had investigated RaBtCoV/4991 in relation to the virus the miners died of they might have prevented the pandemic the world is now struggling under.

Perhaps it was to downplay the fact that they fell down on the job that they opted for a name switch (from RaBtCoV/4991 in 2016 to RaTG13 in 2020), and lack of citation of the 2016 paper. Nothing more sinister is suggested or needed for my argument to go through. There is apparently no way to study the sample of RaTG13 further, since it it is said to have disintegrated upon being sequenced. (I will just call it RaTG13 in what follows.) 8 other SARS-related bat coronaviruses from the mine remain unpublished, to my knowledge.

3. More Mysteries 

Not only is it incredible that no work had been done on RaTG13 in the ensuing years between its discovery and the SARS-CoV-2 outbreak, it turns out to be false! Alina Chan, who describes herself as a molecular biologist turned detective (into origins of SARS-CoV-2), “pointed to an online database showing that the WIV had been genetically sequencing the mine virus in 2017 and 2018, analyzing it in a way they had done in the past with other viruses in preparation for running experiments with them.” (Boston Magazine) (Mystery #6)

But now that we know RaTG13 was sequenced and experimented upon in 2017 and 2018, we are still struck with the mysteries as why they had claimed only to sequence it after the world is hit with the Covid-19 pandemic, and why her close collaborator, Peter Daszak, who for years has funneled money from NIH grants to support the WIV bat coronavirus research, was reporting that the sample was ignored in a freezer for 6 years.[3] Only after the earlier sequencing was revealed did Daszak admit he was wrong. Likewise, it took considerable pressure on Nature before the appearance of a December 2020 addendum to the 2020 article where they admit the earlier experimentation. All very mysterious given that such experimentation would have been expected, since their charge was to investigate specimens with pandemic spillover potential, and since RaTG13 was described by them as having such potential in 2016. So what kind of research were they engaged in?

Some of the experiments — “gain of function” experiments — aimed to create new, more virulent, or more infectious strains of diseases in an effort to predict and therefore defend against threats that might conceivably arise in nature. The term gain of function is itself a euphemism; the Obama White House more accurately described this work as ‘experiments that may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.’ The virologists who carried out these experiments have accomplished amazing feats of genetic transmutation, no question, and there have been very few publicized accidents over the years. But there have been some. (NY Magazine)

There was a moratorium on such research in the U.S. in 2014, but funding was restored in 2017.  Money from U.S. agencies are funneled through Daszak’s organization, the EcoHealth Alliance, to the WIV research team. [The latest award was cut in April 2020, then restored in August 2020.]

Those engaged in such research aver that it is necessary to provide disease surveillance systems to alert us if viruses with pandemic potential are making the jump to humans. Maybe so. But the 2016 paper hid the main details that might have been of use for this. The question isn’t whether this kind of gain of function research could theoretically be useful, but rather whether a specific research group, here, WIV-EcoHealth research, has shown itself to be committed to the transparent behavior necessary to warrant support. It has not.

4. Falsifying the hypothesis of trusted research

What we have is strong, independent pieces of evidence to falsify the group’s claim to good faith commitments to responsibly conduct such research, or even communicate honestly what is known. Were they reliable partners in pandemic research, in the face of the real pandemic we are suffering, they would have bent over backwards to supply explanations for the conflicting admissions, rather than add more obfuscation. Note that nothing more is required to ground my inference. It’s not a matter of showing a lab error or accidental leak. The evidence that falsifies their being good faith stewards to whom we may look to inform, surveil, and help prevent future pandemics is ample. The onus would be on the WIV-EcoHealth research group to come forward with explanations–something one would expect them to be keen to do in order to support the continued research into bat coronaviruses.

Here’s what we know about the value of the WIV-EcoHealth research when it comes to preventing and informing about actual pandemics. We find out that deaths which it turns out they knew from the start were due to a virus–“We suspected that the patients had been infected by an unknown virus” (2020 Addendum)–are not broadcast and in fact there’s a news blackout about the case. A published paper on bat viruses found (2016) does not mention the deaths. Then when a real honest-to-God pandemic from a SARS-like coronavirus comes to light in the city that does major research in the area, the virus is sequenced but given a new name with no mention of the earlier name, let alone the connection with the miners. No it’s worse, there is confusion or prevarication amongst the researchers as to when it has been sequenced, when it has crumbled, and deliberate attempts to conceal records, including taking the central WIV data base off line, preventing further checks. In each case there are denials that only later, after revelations by independent sleuths, result in about-faces. But having declared one thing, it doesn’t ameliorate the situation when the opposite is conceded only in the face of undeniable demonstrations of its falsity. We are still left with conflicting declarations and no explanation for the earlier, opposite stance.

These strange and unscientific actions have obscured the origins of the closest viral relatives of SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2.” (Latham and Wilson)

If it weren’t for the Master’s thesis, the admissions that have come forward might never have occurred.

A co-author of an expert guide to investigating outbreak origins, Dr. Filippa Lentzos, said,

We also need to take a hard look in the mirror. It is our own virologists, funders and publishers who are driving and endorsing the practice of actively hunting for viruses and the high-risk research of deliberately making viruses more dangerous to humans. We need to be more open about the heavily vested interests of some of the scientists given prominent platforms to make claims about the pandemic’s origins. [Chan and Ridley 2021]

The WIV research group has gained the knowledge of how to make a virus more transmissible.[4],[5] One of the existing patents, I read, are for methods that could result in turning a SARS-related coronavirus into SARS-CoV-2. That knowledge hasn’t helped the world control SARS-CoV-2. Good faith sharing of the earlier research would at least have shown the commitment to transparency and ethical research norms. When it comes to the question of the trust that is necessary to endorse future research, the known facts here are actually more troubling than previous cases of lab leaks that were openly admitted and followed by the adoption of improved methods and clear oversights. If this is how a research group behaves when there’s no association between the lab and the pandemic, how much worse can we expect in the case of an actual lab error?

Share your thoughts, links and corrections in the comments.

Mar 4, 2021: I’m adding a new note [6] on the W.H.O. investigation.

Notes

[1] His supervisor, Professor Qian Chuanyun, worked in the emergency department that treated the men. Other details were found in a PhD thesis by a student of the director of the Chinese Centre for Disease Control and Prevention. The full Master’s thesis can also be read in Latham and Wilson 2020 (No paywall).

[2] Details were filled in by independent sleuths throughout the world and “an anonymous Twitter user known as ‘The Seeker’ and a group going by the name of DRASTIC” (Ridley and Chan (2021)). One of the first articles to delineate a possible lab leak is Sirotkin, K. & Sirotkin, D. (2020) https://doi.org/10.1002/bies.202000091.

Rossana Segreto et al. (2020), who identified the identity of RaTG13 and 4991, write:

In late July 2020, Zhengli Shi, the leading CoV researcher from WIV, in an email interview asserted the renaming of the RaTG13 sample and unexpectedly declared that the full sequencing of RaTG13 has been carried out as far back as in 2018 and not after the SARS‐CoV‐2 outbreak, as stated in [her own joint article in February of 2020].

I make no claims about having identified who first found what, as this is not my research area, but if you have an item you think I should reference, I’ll be glad to look at it. Use the comments. Here’s one sent in a comment yesterday by one of the authors:

Rahalkar, M.C.; Bahulikar, R.A. Understanding the Origin of ‘BatCoVRaTG13’, a Virus Closest to SARS-CoV-2. Preprints 2020

[3] Daszak runs a non-government group called the EcoHealth Alliance which disburses funds for research into coronaviruses and other pathogens from U.S. agencies to labs throughout the world. A portion of these grants go to his outfit and he’s one of the most vocal supporters for their continuation. We might even call the research group the WIV-EcoHealth Alliance research group. Understandably many scientists find conflicts of interest in having Daszak leading enquiries into possible Covid lab leak. But he continues to be a key player. Link: https://gmwatch.org/en/news/latest-news/19538-scientists-outraged-by-peter-daszak-leading-enquiry-into-possible-covid-lab-leak.

The worst fears of conflicts of Interest came true upon reading the recent reports on Covid origins. See Mallapaty, S. et al. (2021).

“To find genuinely critical analysis of COVID-19 origin theories one has to go to Twitter, blog posts, and preprint servers. The malaise runs deep when even scientists start to complain that they don’t trust science.”(Latham and Wilson)

[4] Another important name at the cutting edge of gain of function work on bat coronaviruses is Ralph Baric (from UNC). He was perhaps the first to show how to transfer viruses from one species to another. “Not only that, but they’d figured out how to perform their assembly seamlessly, without any signs of human handiwork. Nobody would know if the virus had been fabricated in a laboratory or grown in nature. Baric called this the “no-see’m method.” (New York Magazine).

An eye-opening, excellent (< 10 min) video from leading coronavirologists who know directly of the gain of function experiments. English subtitles. Link: https://twitter.com/learnfromerror/status/1365124271786369025?s=20

[5] Latham and Wilson theorize that the initial virus evolved in the miners themselves during the months-long infection suffered by some of the miners, mimicking the process of serial passaging. This

is a standard virological technique for adapting viruses to new species, tissues, or cell types. It is normally done by deliberately infecting a new host species or a new host cell type with a high dose of virus. This initial viral infection would ordinarily die out because the host’s immune system vanquishes the ill-adapted virus. But, in passaging, before it does die out a sample is extracted and transferred to a new identical tissue, where viral infection restarts. Done iteratively, this technique … intensively selects for viruses adapted to the new host or cell type. ….We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.

(However, there’s no knowledge that the miners transmitted their virus to others around them)

Latham and Wilson’s theory shares analogies with the viral evolution seen in immunocompromised patients https://www.scientificamerican.com/article/covid-variants-may-arise-in-people-with-compromised-immune-systems/.

The same principle underlies the worry about extending the time lag between doses of vaccines. There’s a risk that subimmune individuals with enough antibodies to slow the virus, and perhaps remain asymptomatic, but not enough to wipe it out, could harbor viral variants. https://www.sciencemag.org/news/2021/01/could-too-much-time-between-doses-drive-coronavirus-outwit-vaccines

[6] This post does not continue into the recent investigation of Covid origins (organized, but not necessarily endorsed, by W.H.O.), but it’s clear that the facts discussed here are at the heart of the charges that the inquiry was biased and sorely inadequate. (Problems with alternative zoonotic and frozen food hypotheses add much fuel to the fire.) As the investigation was incapable of uncovering a lab accident or leak, it cannot rule out that hypothesis with any kind of severity. See my comment from March 4 for links to articles out today, and a letter from a group of scientists calling for a brand new, international investigation.

Acknowledgement: I thank Jean Miller for many useful comments, suggestions and corrections on earlier drafts of this post.

References

Arbuthnott, G., Calvert, J.,  & Sherwell, P. (2020). Revealed: Seven year coronavirus trail from mine deaths to a Wuhan lab. The London Times, UK, (July 4, 220 The Sunday Times Insight Investigation).

Baker, N. (2021) The Lab Leak Hypothesis, New York Magazine (January 4, 2021).

Chan, A. Tweetorials on Covid-19 origins: https://twitter.com/Ayjchan/status/1320344055230963712

Chan, A. & Ridley, M. (2021). The World Needs a Real Investigation Into the Origins of Covid-19. The Wall Street Journal  (January 15, 2021).

Ge, XY., Wang, N., Zhang, W. …Shi, Z-L. (2016). Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. Virol. Sin. 31, 31–40 (2016). Link: https://doi.org/10.1007/s12250-016-3713-9

Latham, J. & Wilson, A. (2020). A proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic. Independent Science News for Food and Agriculture website (July 15, 2020).

Mallapaty, S., Maxmen A.,  &  Callaway, E. (2021). “’Major stones unturned’: COVID origin search must continue after WHO report, say scientists”, Nature (February 10, 2021).

[Shi interview, SA] Qui, J. (2020) (June 1, 2020). How China’s ‘Bat Woman’ Hunted Down Viruses from SARS to the New Coronavirus. Scientific American.

Ridley, M. & Chan, A. (2021). Did the Covid-19 virus really escape from a Wuhan lab?. The Telegraph (UK) (February 6, 2021).

Segreto R. & Deigin, Y. (2020). The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin. Bioessays (November 17, 2020). Link: https://doi.org/10.1002/bies.202000240

Sirotkin, K. & Sirotkin, D. (2020). Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?

Xu, L. (2013). The Analysis of Six Patients With Severe Pneumonia Caused By Unknown Viruses (Master’s Thesis). School of Clinical Medicine, Kun Ming Medical University. Translation into English commissioned by Independent Science News, completed June 23, 2020. Link: https://assets.documentcloud.org/documents/6981198/Analysis-of-Six-Patients-With-Unknown-Viruses.pdf

Zhou, P., Yang, XL., Wang, XG. …Shi, Z.(2020).A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273. (February 3, 2020). Link: https://doi.org/10.1038/s41586-020-2012-7

Zhou, P., Yang, XL., Wang, XG. … Shi, Z.(2020) Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 588, E6 (2020). (December 3, 2020). Link: https://doi.org/10.1038/s41586-020-2951-z

Other relevant resources

A fascinating video including come of the key bat coronavirus researchers (short 9 min with English subtitles) https://www.youtube.com/watch?v=-kt9pVYgqkI