ayjchan

In that April slack conversation, the lead author expressed strong, persistent concern about a lab cultured virus that had adapted and become pandemic-ready through that process. Lab culturing = lab manipulation.

Authors have taken their names off papers for much less.

Also, in the accompanying press release from Scripps, Kristian Andersen says:

“These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2.”

https://www.scripps.edu/news-and-events/press-room/2020/2020...

There's no hedging there and it's a press release, meaning it's targeted toward journalists and the public.

The lead author of Proximal Origin wrote this in slack on April 17, a month after the letter had been published in Nature Medicine:

"Okay, so about the current news. Is there any reason to believe that they might be onto something, or is it all smoke and mirrors? Eddie Holmes - any insights on the China side? The main things from my perspective:

1. Bioweapon and engineered totally off the table

2. If there is no engineering and no culturing, then it means that somebody magically found a pre-formed pandemic virus, put it in the lab, and then infected themselves. The prior on that vs somebody coming into contact with an animal source infected with the virus is as close to zero as you can get. Humans come into contact all the time with SARS-like CoVs, but the likelihood of somebody finding exactly that pandemic virus and infecting themselves is very very low (make no mistake - if they did find that pandemic virus. then they would get infected if they grew it in the lab - but the likelihood of them finding it in the first place is exceedingly small (or so one would hope - otherwise, good luck World avoiding future pandemic).

3. But here's the issue - I'm still not fully convinced that no culture was involved. If culture was involved, then the prior completely changes - because this could have happened with any random SARS-llke CoV of which there are very many. So are we absolutely certain that no culture could have been involved? What concerns me here are some of the comments by Shi in the SciAm article ("I had to check the lab" etc) and the fact that the furin site 1s being messed with in vitro. Yes, it loses it but that could be context dependent. Finally, the paper that was shared with us showing a very similar phenomenon (exactly 12bp insertion) in other CoVs has me concerned...

I really really want to go out there guns swinging saying "don't be such an idiot believing these dumb theories - the president is deflecting from the real problems" but I'm warned that we can't fully disprove culture {our argument was mostly based on the presence of the O-linked glycans - but they could likely play a different role... We also can't fully rule out engineering (for basic research) - yes, no obvious signs of engineering anywhere, but that furin site could still have been inserted via gibson assembly (and clearly creating the reverse genetic system isn't hard - the Germans managed to do exactly that for SARS-CoV-2 in less than a month)."

And:

"Shi didn't do any GOF work that I'm aware of - but GOF work isn't the concern here. She did A LOT of work that involved isolating and culturing SARS-like viruses from bats (in BSL-2) and that's my main concerning scenario (we cite several of those in the paper - if you have a look at those original publications, it's definitely concerning work, no question about it - and is the main reason I have been so concerned about the 'culture' scenario)."

I don't think much more needs to be said. The above messages are self-explanatory.

Re: weakening of their claim, not only did Worobey et al. have to remove these instances of unscientific language, but they also had to insert a new study limitations section and this clarification in their article:

“However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there.”

By the time the case definition requirement for a link to the market was removed (Jan 18, 2020), nearly 200 cases had been confirmed. This is not including the number of cases that were suspected/clinically diagnosed.

The 174 cases with onset in Dec 2019 considered by Worobey et al. include both confirmed cases and clinically diagnosed cases. Therefore, most, if not all, of these cases had been identified using the criteria that the patients had to either be linked to the market or, if unlinked to the market, have been identified at hospitals near the market or in the neighborhood of the market.

See: https://archive.ph/LVU6z

See also: https://twitter.com/gdemaneuf/status/1500593644428214272

This is stated most explicitly in the China-WHO joint report (page 42): https://www.who.int/docs/default-source/coronaviruse/who-con...

"In the first days of the epidemic in Wuhan, cases were identified on the basis of clinical features, including fever and acute respiratory symptoms, radiology and epidemiological features. An association with the Huanan market was identified among some of the earliest recognized cases and, for a short period until mid-January 2020, exposure to the Huanan market was included in the case definition. It rapidly became clear, however, that there were cases without a link to the Huanan market, and this element of the definition was dropped a few days after being introduced (Annex E3)."

Yes, there is much more evidence. My medium blog also cites the Chinese CDC in early 2020 and the China-WHO joint report, both of which corroborate the fact that case definitions used in Dec 2019 to mid-Jan 2020 required a link to the market or at least that the patient had to be admitted to a hospital near the market or live in the neighborhood of the market.

See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393104/ https://www.who.int/docs/default-source/coronaviruse/who-con... (pages 125 and 161)

Thanks for the feedback.

On the unlinked cases - if you read my medium post, it explains that even the cases with no connections to the market had been identified with ascertainment bias. Local investigators had searched hospitals and the neighborhood near the market for cases even if they had no link to the market.

On your 2nd point, I've clarified that it was not a rewording but a removal of both claims of dispositive and incontrovertible evidence from the preprint. This means that peer review flagged both of these strong assertions in the manuscript and the authors had to remove both of them.

Here is my evaluation of a recent Science Magazine publication, "The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic".

I'm still an early career scientist so I do not have a way to contact Bill Gates.

We cover this quite extensively in our book. I also have a manuscript that will soon be in peer review describing the relationship between SARS-CoV-2 and other known viruses. None of the publicly disclosed viruses could have plausibly been the progenitor of SARS-CoV-2.

However we now know that when news emerged of a novel SARSrCoV with a novel cleavage site causing an outbreak in Wuhan… scientists in Wuhan did not tell us that they were working with 9 of its closest relatives, linked to mysterious pneumonia cases, and that they had been collecting 1,000s of unpublished high-risk samples from animals & humans across 8 countries, with a clear roadmap for synthesizing consensus SARSrCoV genomes and inserting novel cleavage sites into novel SARSrCoVs. Their database meant to inform pandemic prediction & response remains inaccessible.

Hi, My perspective is that, if the pandemic started due to the virus hunting program which was a very international collaboration (US, China, several European, African, Asian, Middle Eastern countries), then it's not really a China-specific thing. It could just be that China is so much further along in their virus discovery and characterization pipeline (as the scientific literature points out) that unfortunately they were the first to leak one of these pandemic level viruses either found in the wild and sent to the lab or created in the lab during the process of characterization.

I don't think that a country should be singled out for punishment for having a lab accident (unless it can be demonstrated that they do not have proper biosafety protocols and accountability mechanisms in place; a case of reckless negligence). But I do think there should be new international agreements and penalties for suppressing information about an emerging outbreak, e.g., transmissibility of the virus, its genomic sequence, number of cases and geographic spread etc., and costing other countries time in preparing to respond to the outbreak.

Hi Jamal, Yes, there is quite a bit of evidence (photos and interviews of the scientists) showing that the virus hunters in Wuhan did not always wear appropriate protective equipment while hunting for potential pandemic viruses in remote areas. We describe this and provide citations in VIRAL (will be on page 127 in the paperback). In any case, even with full PPE, you can get bitten or exposed to animals and their pathogens. Accidents happen, especially in an uncontrolled environment, e.g., a cave swarming with millions of live bats that you're trying to catch and sample.

Hi,

Thank you for the support! :)

1. The deletion of published data is thankfully not something that commonly happens, but it is not against the rules of the NCBI database. Scientists who deposit their data into the database have the right to ask for that data to be taken down even if it has been published. That's why there is a concern that some scientists may have used this mechanism to delete original data with early Covid-19 sequences in it. Some scientists have called for NCBI to please allow them to search through deleted or suppressed data for these early Covid-19 sequences, but they have not been granted permission. Please see Vanity Fair's report on this: https://www.vanityfair.com/news/2022/03/the-virus-hunting-no...

2. I have seen an archived version of that job posting but, like you said, it didn't surprise me that they were looking for more coronavirologists - the Wuhan Institute of Virology does have one of the world's largest (if not the largest) bat coronavirus hunting programs. The website being revamped kind of goes into speculative territory - maybe it was just time to upgrade the site or maybe they did it to avoid negative attention. The more disturbing thing to me is that they did not share their pathogen database (taken offline in Sep 2019) despite a pandemic happening. The database was meant to help inform pandemic response, but when a real pandemic happened, the database could not be found anywhere. None of their collaborators, including in the US, have seemed to be able to provide a copy.

The vast majority of virologists are not working on gain-of-function research or with potential pandemic pathogens, but this type of research has some very influential backers who control significant sources of funding in virology and infectious diseases. This makes it very awkward and professionally risky for virologists to say that the top leaders in their field advocated for research that might have caused this pandemic and taken millions of lives globally.

National Science Advisory Board for Biosecurity (NSABB) has been reconvened this year to review US government policies on dual use research of concern (DURC) and research with enhanced potential pandemic pathogens (ePPP/P3CO). Their public meeting is available here: https://videocast.nih.gov/watch=44823 Please also see my thread on it: https://twitter.com/Ayjchan/status/1499035660627419139

There is another public engagement session next week. Details here: https://osp.od.nih.gov/event/virtual-stakeholder-engagement-...

Based on these sessions and the history of the NSABB, I'm not confident that they will recommend measures to make this type of research more transparent or even safer.

This is Alina Chan, one of the co-authors of Viral: The Search for the Origin of Covid-19.

I’m going to answer some of the questions that have come up in the comments.

1. Are Chan and Ridley selling a book?

Yes, the updated paperback comes out in the US next week: https://www.harpercollins.com/products/viral-matt-ridleyalin...

The updated epilogue now discusses three significant new developments since the publication of the hardback that are being hotly debated in the comments here. The first was the discovery of a virus in a bat in Laos that is slightly more similar to SARS-CoV-2 than the virus studied at the Wuhan Institute of Virology; but both are still not the progenitor of the pandemic. The second is detailed information about how prominent western virologists, who had privately thought the virus was likely manipulated in a laboratory, began to instead tell the public that no lab-based scenario was plausible. The third is a trio of conflicting studies about whether the Huanan seafood market was the site of a natural spillover of the virus from animals to people or just the site of a human superspreader event in December 2019.

As with the hardcover, half of our earnings from the book have gone/will go to charity.

2. Does the available evidence lean towards a market origin?

Some experts have asserted that there is dispositive evidence that the virus jumped from animals to people at the Wuhan Huanan market. However, their analysis failed to take into account the realities in the early days of the pandemic. Without access to the methodology and actual data collected by investigators in Wuhan, their interpretation unfortunately falls prey to ascertainment bias. Please see this thread for details: https://twitter.com/Ayjchan/status/1499794942012579843

At the moment, US intelligence, the WHO SAGO advisory group, and many top virologists and experts find both natural and lab origin hypotheses plausible and deserving of investigation. The evidence does not lean so strongly towards one hypothesis or the other that we can assume one as the default truth.

I personally think the available evidence points towards a lab origin but would not go as far as to say that there is dispositive evidence of it. Please see these 2 threads: https://twitter.com/Ayjchan/status/1524394197738049537 https://twitter.com/Ayjchan/status/1539745736807616513

3. Can scientists manipulate and genetically engineer naturally found viruses without leaving a trace? In other words, can the genome of the virus tell us its recent history?

We describe the seamless genetic engineering capabilities developed in the years leading up to the pandemic in VIRAL. Due to advanced technologies, it is no longer always possible to use the genome of a virus to distinguish between a natural pathogen vs one that has spent time in a laboratory. Even top coronavirologists, including Ralph Baric who collaborated with the Wuhan scientists, have said that the only way to know is to look at the Wuhan lab records. You can also read my twitter thread: https://twitter.com/Ayjchan/status/1493733086089121794

Even the presence of the furin cleavage site insertion that is unique to the pandemic virus and is indeed what makes it a highly infectious pandemic virus is not “dispositive evidence” of either a natural or lab origin. Please see our peer-reviewed analysis here: https://academic.oup.com/mbe/article/39/1/msab327/6426085

4. Why does the lab leak hypothesis encompass so many different scenarios by which research activities could lead to the emergence of the pandemic virus?

A natural spillover hypothesis also encompasses several different scenarios, e.g., bat direct transmission to people in natural habitats, bat to people in markets, bat to farmed animals or wildlife to people in nature, at farms or market, etc.

This doesn’t mean that a natural or lab origin are insinuations. It just means we are lacking so much key evidence that it’s not possible to pin down an exact mechanism by which the virus emerged in the Wuhan human population.

5. Does finding close relatives of the pandemic virus in bats, e.g., in Laos, mean that its origin is natural?

No, because viruses that escape from labs were also ultimately derived from nature and we know that scientists in Wuhan had been collecting viruses from across 8 countries (China and SE Asia) where the closest relatives to the pandemic virus have been found. Please see the graphic in this tweet: https://twitter.com/Ayjchan/status/1522117270612451335

6. Is there anything to do about finding the origin of Covid-19 now? Isn’t it a dead end? And is that why interest is waning?

There is plenty to do to investigate the origin of Covid-19 using sources and data that exist outside of China. Please see a recent peer-reviewed letter in PNAS: https://www.pnas.org/doi/10.1073/pnas.2202769119

And my thread on it: https://twitter.com/Ayjchan/status/1527381169729425410

It is very surprising to me that these feasible routes of inquiry have not been explored more than 2 years into the pandemic.

7. Have infected animals on sale at the Huanan market been found? Was there any evidence that SARS-like viruses were circulating in the Wuhan animal trading community before the emergence of Covid-19?

No. I recommend reading my medium post for more details: https://ayjchan.medium.com/a-response-to-the-origins-of-sars...

8. Regardless of the origin of Covid-19, shouldn’t the focus be on making sure there is more oversight and regulation of current and future pathogen research?

I agree and wish that we didn’t need to prove the origin of this pandemic to motivate scientific leaders to better regulate risky pathogen work. I have been dedicating efforts to this cause since last year and hope to be able to share some exciting news later this year.

Evolution experiments in the lab mimic natural evolution. The ratio of functional vs silent mutations has also been used to characterize the evolution of viruses under natural selection.

This is Alina Chan, one of the co-authors of Viral: The Search for the Origin of Covid-19.

In defense of a natural origin of Omicron, this study describes the remarkable evolution of SARS-CoV-2 during convalescent plasma treatment of an immunosuppressed patient for 3-4 months; the mutations also reduced sensitivity to neutralizing antibodies: https://www.nature.com/articles/s41586-021-03291-y

We know that there is a large immunocompromised population in Africa and that Covid-19 is rampant there. We also know that most hospitals, regardless of country, don't have the resources to track the evolution of SARS-CoV-2 in their immunocompromised patients. So it's not unexpected that a variant like Omicron could have evolved over an entire year in an immunocompromised individual before finally infecting others.

If there is any evidence that a lab in the region was serially passaging SARS-CoV-2 in neutralizing antibodies/patient serum, then I'd say there is something to go on for a potential lab origin. But at the moment, there is not even circumstantial evidence pointing to this happening in Africa. Maybe setting up a secure channel for whistleblowers with evidence of the above would be the most productive approach.

The above is not to say that I don't think there needs to be much more transparency and accountability from scientists working with pathogens. https://twitter.com/Ayjchan/status/1468582694007279616

Hi Scott,

This is Alina Chan, one of the authors of the book.

Thank you very much for your thorough review of our book :)

On the Laos connection, I made a thread on Twitter to lay out the latest findings about virus samples being sent directly from Laos to Wuhan over several years: https://twitter.com/Ayjchan/status/1476231824267485190?s=20

I hope this is a good update on that point.

Happy new year!