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Evidence SARS-CoV-2 Emerged From a Biological Laboratory in Wuhan, China
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Hibernation #31

Open Nickleaton opened 4 years ago

Nickleaton commented 4 years ago

His next claim is that it is very unlikely that there would be bats naturally living in the metropolitan distict of Wuhan, and in fact no bats were traded at the market at all.

Let us go one step further: there were no bats in Wuhan in December, because bats hibernate in the winter!

=========

I agree - unlikely to be traded. The hibernation applies to bats overflying, dropping infected faeces. Again very unlikely.

However if traded, its easier to catch a hibernating bat than an active one.

angoffinet commented 4 years ago

Bats could have been (probably were, unproven) held in cages at WHCDC, captured by Tian Jun-Hua, or at WIV. Unlikely they could escape, but could infect handlers.

wisefish99 commented 4 years ago

Bats seem to be only one the options for focus anyway. I think there could be more discussion of the likely intermediate host between the bat and the human, which is where scientific inquiry is focused on right now, as the genetic distance between the bat virus and human virus suggest some intermediate spillover event.

It took years for the civet cat to be identified as the intermediate host for SARS CoV-1. This time around, there's been a lot of focus on pangolins, but it's still way too early to say for sure.

It's been pointed out in various analyses that Malayan pangolins are (illegally) imported into Southern China for sale in wildlife markets there.

angoffinet commented 4 years ago

Together with a colleague in Paris, I am investigating the pangolin data. All I can say at this stage is that the pangolin as intermediate host is most probably wrong. Indeed, it looks like chinese authorities themselve have stopped promoting that hypothesis. Honestly, accidental leak from a lab of a virus that has been adapted (not necessarily engineered) to grow in human cells is more likely than any bat-intermediate mammal -human chain.

wisefish99 commented 4 years ago

So the first article that talked about pangolins was this one:

https://pubs.acs.org/doi/10.1021/acs.jproteome.0c00129

Key concluding statement:

Whereas the current evidence mainly points to the pangolin as the most likely intermediate host, it is possible for other animals to also serve as intermediate hosts for the following two reasons. First, coronaviruses are known to have multiple intermediate hosts. For example, SARS-CoV, of which the palm civet (Paguma larvata) is the most well-known intermediate host, is also reported to use a raccoon dog (Nyctereutes procyonoides) and a ferret badger (Melogale moschata) as intermediate hosts.(46) Second, the 91% sequence identity between the Manis coronavirus and 2019-nCoV is high enough to confirm an evolutionary relation between the two viruses but not high enough to consider them as the same viral species. To put this into perspective, the viral sequence from intermediate hosts of SARS-CoV and MERS-CoV are 99.8 and 99.9% identical to their human versions, respectively.(46,47) Therefore, even with the discovery of Manis coronavirus, further searching for other potential intermediate hosts should be continued.

But then, you are correct that more recent China-USA joint research has not agreed with this conclusion:

https://www.biorxiv.org/content/10.1101/2020.02.18.954628v1.full

Concluding quote:

In the last two decades, besides the 2019-nCoV, SARS and MERS caused serious outbreaks in humans, lead to thousands of deaths [3, 4, 13, 14]. Although all of three zoonotic coronaviruses were shown to be of bat origin, they seemed to use different intermediate hosts. For example, farmed palm civets were suggested to be an intermediate host for SARS to be spilled over to humans although the details on how to link bat and farmed palm civets are unclear [15, 16, 17]. Most recently, dromedary camels in Saudi Arabia were shown to harbor three different coronavirus species, including a dominant MERS-CoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015 [18]. Although this present study does not support pangolins would be an intermediate host for the emergence of the 2019-nCoV, our results do not prevent the possibility that other CoVs could be circulating in pangolins. Thus, large surveillance of coronaviruses in the pangolins could improve our understanding the spectrum of coronaviruses in the pangolins. Conservation of wildlife and limits of the exposures of humans to wildlife will be important to minimize the spillover risks coronaviruses from wild animals to humans.

In summary, this study suggested pangolins be a natural host of Betacoronavirus, with an unknown potential to infect humans. However, our data do not support the 2019-nCoV evolved directly from the pangolin-CoV.

Both studies still do strongly support the conclusion that there was SOME intermediary host between bat and human, and this is the current general consensus among the scientific community at large too.

https://www.bbc.com/news/science-environment-52529830

Considering SARS-CoV-1, just 17 years ago, was passed on via bat - intermediate mammal - human, I'm not sure why you consider accidental leak from a laboratory to be more plausible than such an event occurring again .

angoffinet commented 4 years ago

I would be glad to agree with you if we had serious evidence for the elusive intermediate host. To me, pangolins are now excluded, but there are other possibilities worth testing. We know that Cov2 infects mustelids (ferrets, badgers etc...) very easily and there were probably mustelids for sale in various market places, in Wuhan probably. There is also the so-called raccoon dog, susceptibility of which has perheps been tested but not published. So, yes, an intermediate host cannot be excluded and I know many of my colleagues still favor that hypothesis, like you do.

All I am saying is that a leak is also plausible and should be investigated. Yet, chinese authorities steadfastly refuse even the smallest comment along that line. They ignore that, to know what truly happened is in the interest of chinese people as well everyone else. So, whay are they so reluctant to discuss anything if they have nothing to hide?

We all agree that Sars1 passed from civets (and perhaps other hosts), but this was in South China (Guangdong, HK) where eating wild derived animals is more common than in Wuhan. Then why did the outbreak start just in Wuhan, the place where there are the two main teams working on bat coronaviruses (WIV and WHCDC)?

And finally, why should we be eager to believe what chinese officials tell us about the origin of the virus, when we know for sure that they lied a lot about the epidemic (dates, number of death, severity of symptoms, etc...).

We need to know the truth and should consider ALL possibilities, not just what chinese authorities tell us.

Nickleaton commented 4 years ago

You need to evaluate the probabilities of each event. Namely why did the virus home in on the wet market next to a virus lab a few months after they started their research? Or given that there are over 100,000 wet markets in China operating for decades it picked the wet market in Wuhan? Of all the gin joints in all the towns in all the world... https://www.youtube.com/watch?v=Qa8d-jwFwds

On Wed, 6 May 2020 at 12:53, Andre Goffinet notifications@github.com wrote:

I would be glad to agree with you if we had serious evidence for the elusive intermediate host. To me, pangolins are now excluded, but there are other possibilities worth testing. We know that Cov2 infects mustelids (ferrets, badgers etc...) very easily and there were probably mustelids for sale in various market places, in Wuhan probably. There is also the so-called raccoon dog, susceptibility of which has perheps been tested but not published. So, yes, an intermediate host cannot be excluded and I know many of my colleagues still favor that hypothesis, like you do.

All I am saying is that a leak is also plausible and should be investigated. Yet, chinese authorities steadfastly refuse even the smallest comment along that line. They ignore that, to know what truly happened is in the interest of chinese people as well everyone else. So, whay are they so reluctant to discuss anything if they have nothing to hide?

We all agree that Sars1 passed from civets (and perhaps other hosts), but this was in South China (Guangdong, HK) where eating wild derived animals is more common than in Wuhan. Then why did the outbreak start just in Wuhan, the place where there are the two main teams working on bat coronaviruses (WIV and WHCDC)?

And finally, why should we be eager to believe what chinese officials tell us about the origin of the virus, when we know for sure that they lied a lot about the epidemic (dates, number of death, severity of symptoms, etc...).

We need to know the truth and should consider ALL possibilities, not just what chinese authorities tell us.

— You are receiving this because you authored the thread. Reply to this email directly, view it on GitHub https://github.com/Project-Evidence/project-evidence.github.io/issues/31#issuecomment-624604774, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAF7NEHSULODQQDBSNE5HITRQFFS3ANCNFSM4MYUF6PQ .

-- Nick

wisefish99 commented 4 years ago

All I am saying is that a leak is also plausible and should be investigated. Yet, chinese authorities steadfastly refuse even the smallest comment along that line. They ignore that, to know what truly happened is in the interest of chinese people as well everyone else. So, whay are they so reluctant to discuss anything if they have nothing to hide?

I would say they have discussed it, by saying: "those allegations that it escaped from a laboratory are not true". The WIV said this, the relevant foreign spokespeople have said this. Now obviously you don't like that answer, but that doesn't mean they haven't discussed it. What would you have them do instead? If the theory is false, then from their perspective it's incredibly insulting for them to have to "prove the innocence" of their laboratory and its scientists and researchers. The burden of proof is on the accusers, not the accused.

And as you correctly point out, Beijing is indeed very interested in finding the origin of the virus. If they could confirm that it was released from the WIV or the CDC lab, even accidentally, you think the people working there would still have jobs? You think they would still be walking free? Of course not...they'd be in jail or worse...

We all agree that Sars1 passed from civets (and perhaps other hosts), but this was in South China (Guangdong, HK) where eating wild derived animals is more common than in Wuhan. Then why did the outbreak start just in Wuhan, the place where there are the two main teams working on bat coronaviruses (WIV and WHCDC)

I personally am inclined toward the theory that it DIDN'T start in Wuhan, but in Guangdong, but spread most virulently in Wuhan. I have been sharing and discussing a relevant study from a Cambridge research team in a different Issues thread. I realize I'm kind of "going against the flow" here, and it's obvious you guys have put a lot of time and effort in preparing the primary theory, but I hope there's still space for consideration of other origin theories.

I'm not a scientist by any means, but I am an American who has lived in China for nearly a decade and am fluent in Mandarin, so hope I can bring some additional context or variety of perspective to the discussion. I'd like to think I'm pretty objective, but that obviously is a subjective assessment...

https://github.com/Project-Evidence/project-evidence.github.io/issues/29#issuecomment-624538127

And finally, why should we be eager to believe what chinese officials tell us about the origin of the virus, when we know for sure that they lied a lot about the epidemic (dates, number of death, severity of symptoms, etc...).

I'm not sure which Chinese officials you're referring to here. There are many hierarchies of "Chinese officials" and China itself is not a hive mind..it's made up of individual people with their own motivations and plans. It's possible for some people to know things and conceal them from other people in China.

As for lying...well if you believe the CCP is truly evil, then you'll always believe the worst, and that everything that comes out of a Beijing official's mouth is a lie.

I don't have such a negative impression, nor do I think the assertion that "they lied a lot about the epidemic (dates, number of death, severity of symptoms)" is warranted. There were major problems in the early stages of the response, both intentional and accidental, but the blame seems more likely to fall on municipal and provincial leadership of Wuhan and Hubei, respectively. Obstructing the flow of information to the central government, stifling doctors, and failing to take aggressive preventative measures on a city level were unmistakably wrong. Note that quite a few of those responsible officials have been fired. The day after Beijing dispatched an inspection team to Wuhan led by Zhong Nanshan (Jan 20), the press conference was held, where human-to-human transmission was confirmed.

Starting from that date, we got very comprehensive daily data on a provincial, city, and district basis, of how many confirmed cases, suspected cases, deaths, and recovered cases there were. I have seen no convincing evidence of INTENTIONAL cover-up of number of deaths or severity of symptoms since that point. Assertions to the contrary have been conspiracy theories with no sound basis in reality, usually promoted by people who don't understand the scale and effectiveness of the epidemic prevention methods that were applied in China, starting from January 20.

Nickleaton commented 4 years ago

Wrong. The balance of probability is by a considerable margin that it came out of the lab.

= The day after Beijing dispatched an inspection team to Wuhan led by Zhong Nanshan (Jan 20), the press conference was held, where human-to-human transmission was confirmed.

Doesn't prove anything about the lab being the source

= I have seen no convincing evidence of INTENTIONAL cover-up of number of deaths

Plenty of evidence available from the number of cremations, to the mismatch between the numbers reported from China compare to elsewhere.

Why would China refuse access to inspectors to inspect the lab? Answer they have a lot to hide.

= Note that quite a few of those responsible officials have been fired.

And those responsible for the lab? Are they still alive?

On Wed, 6 May 2020 at 14:39, wisefish99 notifications@github.com wrote:

All I am saying is that a leak is also plausible and should be investigated. Yet, chinese authorities steadfastly refuse even the smallest comment along that line. They ignore that, to know what truly happened is in the interest of chinese people as well everyone else. So, whay are they so reluctant to discuss anything if they have nothing to hide?

I would say they have discussed it, by saying: "those allegations that it escaped from a laboratory are not true". The WIV said this, the relevant foreign spokespeople have said this. Now obviously you don't like that answer, but that doesn't mean they haven't discussed it. What would you have them do instead? If the theory is false, then from their perspective it's incredibly insulting for them to have to "prove the innocence" of their laboratory and its scientists and researchers. The burden of proof is on the accusers, not the accused.

And as you correctly point out, Beijing is indeed very interested in finding the origin of the virus. If they could confirm that it was released from the WIV or the CDC lab, even accidentally, you think the people working there would still have jobs? You think they would still be walking free? Of course not...they'd be in jail or worse...

We all agree that Sars1 passed from civets (and perhaps other hosts), but this was in South China (Guangdong, HK) where eating wild derived animals is more common than in Wuhan. Then why did the outbreak start just in Wuhan, the place where there are the two main teams working on bat coronaviruses (WIV and WHCDC)

I personally am inclined toward the theory that it DIDN'T start in Wuhan, but in Guangdong, but spread most virulently in Wuhan. I have been sharing and discussing a relevant study from a Cambridge research team in a different Issues thread. I realize I'm kind of "going against the flow" here, and it's obvious you guys have put a lot of time and effort in preparing the primary theory, but I hope there's still space for consideration of other origin theories.

I'm not a scientist by any means, but I am an American who has lived in China for nearly a decade and am fluent in Mandarin, so hope I can bring some additional context or variety of perspective to the discussion. I'd like to think I'm pretty objective, but that obviously is a subjective assessment...

29 (comment)

https://github.com/Project-Evidence/project-evidence.github.io/issues/29#issuecomment-624538127

And finally, why should we be eager to believe what chinese officials tell us about the origin of the virus, when we know for sure that they lied a lot about the epidemic (dates, number of death, severity of symptoms, etc...).

I'm not sure which Chinese officials you're referring to here. There are many hierarchies of "Chinese officials" and China itself is not a hive mind..it's made up of individual people with their own motivations and plans. It's possible for some people to know things and conceal them from other people in China.

As for lying...well if you believe the CCP is truly evil, then you'll always believe the worst, and that everything that comes out of a Beijing official's mouth is a lie.

I don't have such a negative impression, nor do I think the assertion that "they lied a lot about the epidemic (dates, number of death, severity of symptoms)" is warranted. There were major problems in the early stages of the response, both intentional and accidental, but the blame seems more likely to fall on municipal and provincial leadership of Wuhan and Hubei, respectively. Obstructing the flow of information to the central government, stifling doctors, and failing to take aggressive preventative measures on a city level were unmistakably wrong. Note that quite a few of those responsible officials have been fired. The day after Beijing dispatched an inspection team to Wuhan led by Zhong Nanshan (Jan 20), the press conference was held, where human-to-human transmission was confirmed.

Starting from that date, we got very comprehensive daily data on a provincial, city, and district basis, of how many confirmed cases, suspected cases, deaths, and recovered cases there were. I have seen no convincing evidence of INTENTIONAL cover-up of number of deaths or severity of symptoms since that point. Assertions to the contrary have been conspiracy theories with no sound basis in reality, usually promoted by people who don't understand the scale and effectiveness of the epidemic prevention methods that were applied in China, starting from January 20.

— You are receiving this because you authored the thread. Reply to this email directly, view it on GitHub https://github.com/Project-Evidence/project-evidence.github.io/issues/31#issuecomment-624655390, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAF7NEGHXNGLRDLATPLYJHLRQFSA7ANCNFSM4MYUF6PQ .

-- Nick

angoffinet commented 4 years ago

Let us avoid nastly feelings. All ideas are worth hearing and considering. I have been working with chinese colleagues, including going in their lab in Guangzhou, for more than 10 years, but was unable to learn the language, even tough I tried very hard. I met very nice people there, but lots of students around the labs that makes it difficult to work cleanly most of the time. Quite far from standards in USA and Europe. To work under P4, even P3 conditions is not easy and requires a lot of training. I personally belive that colleagues like Zhenli Shi are competent and smart. But I don't see how they can follow all those students in and out of labs. Accidents become almost unavoidable.

wisefish99 commented 4 years ago

Plenty of evidence available from the number of cremations, to the mismatch between the numbers reported from China compare to elsewhere.

Increase in cremations in March-April were from all the accumulated deaths from all causes after three months of no funeral services in Wuhan, starting in late January.

Numbers reported in China track closely with numbers in other countries that had effective and competent responses, and took aggressive preventative measures. Or maybe you believe New Zealand and South Korean governments are lying...?

Nickleaton, I want to keep the conversation going with people who are open-minded, and who want to derive a conclusion from facts, and not go looking for facts to support a conclusion they already have in mind.

When you take the latter approach, you are more inclined to treat bad evidence as good evidence and abandon objectivity and the scientific approach. If this is your choice for this exercise, I will exercise my right to not engage with you in the future.

Nickleaton commented 4 years ago

I'm going for the most probable explanation and its that the virus leaked.

Now read the other posts in this chain. I'll quote it so you understand exactly what the point is

The name of the poster matches a known researcher, albeit a neurobiologist, not a virologist.

He's saying that accidents are almost unavoidable. I believe that to be accurate. So the question is why Zhenli Shi and go were taking the risks? The risks have killed lots of people. They weren't competent or smart enough.

In particular, genetically engineering corona viruses to make them more SARs is completely idiotic when accidents are unavoidable.

N.

Let us avoid nastly feelings. All ideas are worth hearing and considering. I have been working with chinese colleagues, including going in their lab in Guangzhou, for more than 10 years, but was unable to learn the language, even tough I tried very hard. I met very nice people there, but lots of students around the labs that makes it difficult to work cleanly most of the time. Quite far from standards in USA and Europe. To work under P4, even P3 conditions is not easy and requires a lot of training. I personally belive that colleagues like Zhenli Shi are competent and smart. But I don't see how they can follow all those students in and out of labs. Accidents become almost unavoidable. The

On Wed, 6 May 2020 at 15:15, wisefish99 notifications@github.com wrote:

Plenty of evidence available from the number of cremations, to the mismatch between the numbers reported from China compare to elsewhere.

Increase in cremations in March-April were from all the accumulated deaths from all causes after three months of no funeral services in Wuhan, starting in late January.

Numbers reported in China track closely with numbers in other countries that had effective and competent responses, and took aggressive preventative measures. Or maybe you believe New Zealand and South Korean governments are lying...?

Nickleaton, I want to keep the conversation going with people who are open-minded, and who want to derive a conclusion from facts, and not go looking for facts to support a conclusion they already have in mind.

When you take the latter approach, you are more inclined to treat bad evidence as good evidence and abandon objectivity and the scientific approach. If this is your choice for this exercise, I will exercise my right to not engage with you in the future.

— You are receiving this because you authored the thread. Reply to this email directly, view it on GitHub https://github.com/Project-Evidence/project-evidence.github.io/issues/31#issuecomment-624666673, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAF7NEDHCBS2JK562MHFF7TRQFWG5ANCNFSM4MYUF6PQ .

-- Nick

f-pound commented 4 years ago

There has been quite a bit of discussion about the 12 nucleotide insertion at positions 681-684. The most closely related virus sample is from bat-RaTG13 but it does not contain that insertion.

"The alignment shows that 2019-nCoV contains a four amino acid insertion 681PRRA684 that is not found in any other sequences, including the closely related bat-SL-RaTG13 (Fig. 2B)."

https://www.biorxiv.org/content/10.1101/2020.02.10.942185v1.full "The four amino acid insertion feature appears unique among lineage B viruses, as all other species analyzed in the extended alignment, none contained the stretch of basic residues identified in 2019-nCoV S"

This insertion seems to be unique in C variants as well as some in the A variants. Those variants dominated by MERS.

"To our knowledge, the enlarged priming loop of 2019-nCov is unique among the viruses in Betacoronavirus lineage C. The presence of a distinct insert containing paired basic residues in the S1/S2 priming loop is common in many coronaviruses in Betacoronavirus lineage C (e.g. MERS-CoV), as well as in lineage A (e.g. mouse hepatitis virus, MHV) and lineage d, and is universally found in Gammacoronavirus S (e.g. IBV) (Shang et al., 2018). "

Because 2019-nCov contains uncanny resemblance to RatG13 (97%) but missing the insertion which is very much like what is seen in MERS; one hypothesis is that the jump happened when recombination happened between a carrier of RatG13 which was also infected with MERS. Perhaps this is the missing link? What is the probability of this occurring in nature versus an experiment in a lab where insertions like this are done on a regular basis in order to study enhanced function and inform vaccine development.

Evidence of experiments where viruses with out the insertion were used to test such an insertion: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911587/ To test whether H9 HA is able to accommodate such modification, we substituted the original H9 cleavage site of Israel810 with H5 and H7 HPAI cleavage sites (Fig. 7A). Three constructs were made to mimic the H5N1 HPAI polybasic cleavage site (PB), the 11-amino-acid insertion mimicking HPAI H7N3 isolated in British Columbia in 2004 (45) with a dibasic cleavage site (Insert+DB) or the same insertion with a tribasic cleavage site (Insert+TB) (Fig. 7A).

With the caveat: "Whether this mutation combination translates into a highly pathogenic virus remains to be tested. Such studies should only be carried out under highly prescribed biosafety conditions and with appropriate administrative oversight. At present, our work is important in the context of influenza pandemic planning."

While others suggest that this is natural: https://www.biorxiv.org/content/10.1101/2020.02.08.926006v3.full "By the way, some researchers previously supposed the SARS-CoV-2 was artificial due to four inserts in the S protein of SARS-CoV-2 from HIV sequence. However, the results of protein sequence alignment revealed that the similar sequence of the reported fourth insertion site (680-SPRR-683) in SARS-CoV-2 was commonly found in many beta-coronavirus. Therefore, we supposed that based on the current evidence, it is not scientific to consider the insertion sequence in SARS-CoV-2 S protein being artificial."

And lastly a warning by US CDC which instructs lab workers involved in Avian Flu researchers should NOT be around domestic or wild birds: https://web.archive.org/web/20130610161602/http://www.cdc.gov/flu/avianflu/h7n9/risk-assessment.htm "To prevent the potential spread of this virus to birds, personnel working in the BSL-3 laboratory with influenza A(H7N9) viruses must avoid contact with domestic or wild birds. All laboratorians working with influenza A(H7N9) viruses should comply with USDA policy of having no contact with any avian species or their housing when away from the workplace for at least five days after the last day of work on this virus in the laboratory. This includes home pets (e.g., canaries, parakeets, parrots) and poultry on farms and in backyards."

Lots to digest. But the points are as follows:

  1. There is a unique insertion in the 2019-nCov virus which has been seen in all mutations to date. This insertion makes 2019-nCov highly virulent because it allows for easy cleaving of the insertion site to allow for virus entry into host cells.
  2. The 12 nucleotide insertion is common in MERS type viruses but not in the family of 2019-nCov; even the closest neighbor RatG13 doesn't contain this insertion.
  3. Lab experiments have and still regularly occur specifically with insertion of poly basic furin cleavage sites in order to add function to existing corona viruses.
  4. Specific papers say that this type of research is very dangerous
  5. US CDC says that lab workers SHOULD not visit areas where vulnerable animal populations exist.
  6. Why didn't US CDC not say to quarantine for 5 days period; does this indicate that the virus is incapable of jumping species or that it was an extreme low risk? If an extreme low risk...then why is this the primary counter point to the virus originating in the lab?

Best Regards to everyone spending every waking moment trying to solve this very mysterious puzzle.

angoffinet commented 4 years ago

This is the so-called furin site. Furin is a proteolytic enzyme that can cleave and thereby poise the spike protein when the virus is excreted by infected cells. The poised virus is more prone to infect cells. Furing sites make flu viruses more virulent. Not sure this is shown with coronaviruses, although very likely. A furing site could probably be acquired during culture or passage of virus in animal and cell lines, and/or by recombination between different viruses, or by lab modification of the virus (GOF experiments). Everything is possible.

Thank you for the link to CDC warning about avian flu. My intuition is that a similar warning should apply to SARS-CoV-2. Alarmingly, the new virus is currently used in several places, especially in veterinary labs, to infect domestic animals. I was flabberghasted to read in Science that it has been done in Harbin, and suspect it might have aggravated the epidemic there. I am not frightened to hear that it is done in other places. For example in Belgium they infected hamsters and showed the virus can take.

f-pound commented 4 years ago

I'm pretty sure this was posted here but I can't remember so posting again just in case. This is some research done by Daoyu Zhang who questions the validity of the RatG13 and MP789 close matches to SARS-COV2/2019-nCov. HIs work is very convincing and in fact supports my prior intuition where I thought it was quite suspicious that the bat sample RatG13 collected in 2013 was only recently sequenced in 2020? It is the ONLY sample and interestingly is only significantly off a complete match of sars-cov2 by 12 nucleotides.

https://docs.google.com/document/d/1opowSQgcvpSb58piY1mvSf4AIGzpjssS/edit#

"The origin of SARS-CoV-2, the agent that causes the global pandemic known as COVID-19, is of both heated Academic debate and political debate. As this directly affect policy decision and global politics, this matter must be considered with uttermost scrutiny. The leading academic hypothesis of the origin was that of a natural recombination event between the Bat coronavirus RaTG13 and the pangolin coronavirus MP789, followed by adaptation in humans after zoonotic transfer. However, this theory hinges critically on the validity of both RaTG13 and MP789, which require both strains to be able to be independently sequenced, tested and validated for infectivity of it’s original host. Here we provide evidence that the validity of both strains are highly dubious and are incapable of sufficing the required conditions for both to be considered valid evidence for the hypothesis of a natural origin of SARS-CoV-2. "

"By using sequence analysis and computational-based analysis, the validity of both RaTG13 and MP789 as evidence for deducing the origin of SARS-CoV-2 were discredited on the basis of both the lack of independent verifiability and the lack of credibility of the sequences on a molecular basis. Unless such samples can be independently sequenced and verified by an institution, scientist or a group of scientists without connection to nor conflict of interest with the original publisher of the sequences, any study that uses such sequences as evidence to deduce the origin of SARS-CoV-2 should be discredited and rejected for use as basis for policy-making decisions. "

f-pound commented 4 years ago

Also this point shouldn't be missed....the RatG13 sample in the BLAST nucleotide search results below IS THE ONLY ONE. If bats were being researched en-masse why is there ONLY a single sample of this genome?

Select seq MN996532.1 Bat coronavirus RaTG13, complete genome 55132 55132 100% 0.0 100.00% MN996532.1 Select seq MT385429.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/CA-CZB-IX00079/2020, complete genome 48730 48730 100% 0.0 96.12% MT385429.1 Select seq MT385424.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/CA-CZB-IX00103/2020, complete genome 48730 48730 100% 0.0 96.12% MT385424.1 Select seq MT385421.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/CA-CZB-IX00015/2020, complete genome 48730 48730 100% 0.0 96.12% MT385421.1 Select seq MT385419.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/CA-CZB-IX00133/2020, complete genome 48730 48730 100% 0.0 96.12% MT385419.1 Select seq MT358675.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/WA-UW-3810/2020, complete genome 48730 48730 100% 0.0 96.12% MT358675.1 Select seq MT114417.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/HKG/HKU-907b/2020, complete genome 48730 48730 100% 0.0 96.12% MT114417.1

angoffinet commented 4 years ago

That analysis is extremely well done. It confirms what I found, namely that there seems to be only ONE pangolin sequence, of poor quality, that codes the same RBD as SARS-CoV2. Do you know if Daoyu Zhang has contacted Nature and/or tried to publish his analysis. It should be public. Maybe you can ask him to get in touch with me if he wants? Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le ven. 8 mai 2020 à 14:52, Frank Pound notifications@github.com a écrit :

I'm pretty sure this was posted here but I can't remember so posting again just in case. This is some research done by Daoyu Zhang who questions the validity of the RatG13 and MP789 close matches to SARS-COV2/2019-nCov. HIs work is very convincing and in fact supports my prior intuition where I thought it was quite suspicious that the bat sample RatG13 collected in 2013 was only recently sequenced in 2020? It is the ONLY sample and interestingly is only significantly off a complete match of sars-cov2 by 12 nucleotides.

https://docs.google.com/document/d/1opowSQgcvpSb58piY1mvSf4AIGzpjssS/edit#

"The origin of SARS-CoV-2, the agent that causes the global pandemic known as COVID-19, is of both heated Academic debate and political debate. As this directly affect policy decision and global politics, this matter must be considered with uttermost scrutiny. The leading academic hypothesis of the origin was that of a natural recombination event between the Bat coronavirus RaTG13 and the pangolin coronavirus MP789, followed by adaptation in humans after zoonotic transfer. However, this theory hinges critically on the validity of both RaTG13 and MP789, which require both strains to be able to be independently sequenced, tested and validated for infectivity of it’s original host. Here we provide evidence that the validity of both strains are highly dubious and are incapable of sufficing the required conditions for both to be considered valid evidence for the hypothesis of a natural origin of SARS-CoV-2. "

"By using sequence analysis and computational-based analysis, the validity of both RaTG13 and MP789 as evidence for deducing the origin of SARS-CoV-2 were discredited on the basis of both the lack of independent verifiability and the lack of credibility of the sequences on a molecular basis. Unless such samples can be independently sequenced and verified by an institution, scientist or a group of scientists without connection to nor conflict of interest with the original publisher of the sequences, any study that uses such sequences as evidence to deduce the origin of SARS-CoV-2 should be discredited and rejected for use as basis for policy-making decisions. "

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research-project-cov commented 4 years ago

this article suggests bats migrated 800km attracted by green light of Wuhan Yantze bridge; https://www.mdpi.com/1660-4601/17/5/1633 the same article confirmes no bats sold at the Wuhan market; it also says the dead panglolin with COV was cought in antismugling opetation at frontiere with malaysia; the analysed pangolin came from malaysia; I myself saw pangolins in Yunnan, China, some 20 years ago; never in Wuhan; Pangolins shells could have been brought to Wuhan for use in chinese traditional medecines. I do not see other way.

Nickleaton commented 4 years ago

Andre,

It's it far more likely as you said, that the virus, a novel natural variant, or genetically modified left the lab? After all you've said there very little chance of it being stopped?

What's going on with the GM view is the idea if its show not to be GM, they will then claim its not left the lab.

It may well have been one of the novel variants they collected in the wild, brought into an insecure lab, and it escaped.

On Sat, 9 May 2020 at 07:32, Andre Goffinet notifications@github.com wrote:

That analysis is extremely well done. It confirms what I found, namely that there seems to be only ONE pangolin sequence, of poor quality, that codes the same RBD as SARS-CoV2. Do you know if Daoyu Zhang has contacted Nature and/or tried to publish his analysis. It should be public. Maybe you can ask him to get in touch with me if he wants? Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le ven. 8 mai 2020 à 14:52, Frank Pound notifications@github.com a écrit :

I'm pretty sure this was posted here but I can't remember so posting again just in case. This is some research done by Daoyu Zhang who questions the validity of the RatG13 and MP789 close matches to SARS-COV2/2019-nCov. HIs work is very convincing and in fact supports my prior intuition where I thought it was quite suspicious that the bat sample RatG13 collected in 2013 was only recently sequenced in 2020? It is the ONLY sample and interestingly is only significantly off a complete match of sars-cov2 by 12 nucleotides.

https://docs.google.com/document/d/1opowSQgcvpSb58piY1mvSf4AIGzpjssS/edit#

"The origin of SARS-CoV-2, the agent that causes the global pandemic known as COVID-19, is of both heated Academic debate and political debate. As this directly affect policy decision and global politics, this matter must be considered with uttermost scrutiny. The leading academic hypothesis of the origin was that of a natural recombination event between the Bat coronavirus RaTG13 and the pangolin coronavirus MP789, followed by adaptation in humans after zoonotic transfer. However, this theory hinges critically on the validity of both RaTG13 and MP789, which require both strains to be able to be independently sequenced, tested and validated for infectivity of it’s original host. Here we provide evidence that the validity of both strains are highly dubious and are incapable of sufficing the required conditions for both to be considered valid evidence for the hypothesis of a natural origin of SARS-CoV-2. "

"By using sequence analysis and computational-based analysis, the validity of both RaTG13 and MP789 as evidence for deducing the origin of SARS-CoV-2 were discredited on the basis of both the lack of independent verifiability and the lack of credibility of the sequences on a molecular basis. Unless such samples can be independently sequenced and verified by an institution, scientist or a group of scientists without connection to nor conflict of interest with the original publisher of the sequences, any study that uses such sequences as evidence to deduce the origin of SARS-CoV-2 should be discredited and rejected for use as basis for policy-making decisions. "

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angoffinet commented 4 years ago

Impossible to prove, until we have sequences of different virus isolates. Apparently, the novel virus in Harbin is different than the strains used to infect domestic animals in the Harbin P4 lab (published in Global China, an official journal). So, there are different possibilities that could in principle be checked. 1.If the Harbin strain was imported from New York, then the sequence should resemble the NY virus more than the Wuhan strain.

  1. If it was a re-entry from Siberia, then it should resemble virus isolated from cases in Siberia. 3.If it was an accidental leak from P4, then the virus should resemble virus secreted by infested animals in the P4. Also, sick people should then be traced to contacts at the Vet Institute and its P4. In sum, all this is testable, and the only problem is that chinese officials steadfastly refuse any investigation. Even though that would be (in the end) in the interest of the chinese people as well as the rest of us.
nemonominem commented 4 years ago

angofinet, what do you make of this study? Is it scientifically sound?

https://medium.com/@yurideigin/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748

angoffinet commented 4 years ago

Thank you for your question. I read this some time ago and it is very well documented and accurate as far as I can tell (although the author has a somewhat strange personality - if you check on the web yourself). It shows that SARS-CoV-2 could have been modified from a bat coronavirus at the WIV in Wuhan. And then leaked by lax laboratory procedures. From what I read, the leak is highly plausible given that: 1) the virus is highly contagious; and 2) some procedures in laboratories in China are less stringent than in the west. Has the virus been modified to test how it adapts to human? This is technically doable as shown by the paper you refer here, and given that attempts at doing such GOF experiments have been made in different places in addition to WIV (e.g. Baric lab in the USA). Importantly, what everybody agrees on is that, even if it was a leak, there was nothing intentional, no bioweaponizing or anything like this. Just a small accident with huge consequences. Since the whole world is concerned, this is not an internal chinese affair, and it should be INVESTIGATED. Not to "punish", but to make sure it does not happen again. All GOF experiments should be dependent on authorization by an international body (modelled on atomic energy perhaps?).

nemonominem commented 4 years ago

Thanks. I fully agree with the 'accidental' conclusion. One should not underestimate the possibilities of Murphy's law combined with sloppy practices.

If China has plans (like any major power I would suspect) to weaponize viruses, it would likely still be a few years down the line and most likely in another lab. So there is no real need to go there.

angoffinet commented 4 years ago

There is also Hanton's razor "Never attribute to malice that which is adequately explained by stupidity" (or "incompetence") . I am still naive enough to believe that nobody is engineering viruses as weapons, at least not among countries who signed the bioweapon treaties. Terror states is another matter. But let us now focus on China allowing investigations in Wuhan to know what happened and take appropriate measures.

angoffinet commented 4 years ago

Sorry for the typo, it is Hanlon razor...

Nickleaton commented 4 years ago

Gilles,

I would agree. It's well know that weaponising biological weapons is most likely to kill your own side first.

What I suspect is that the researchers didn't appreciate the risks. They started off with something completely safe. That worked so they made a small step. Then another, then another towards more and more risky experiments. Since it was already 'safe' a small change can't be risky. If they had evaluated the complete experiment, rather than the changes, its likely they would not have done what they did.

It's the same thinking in any financial con. You don't go for the payoff, you have to layer it. Build up to the con, in small steps Each step, each increment, is reasonable. But the leap from start to finish would be immediate rejected if you approach it that way.

In effect they have conned themselves.

The accidental release also points at one thing. There's lots of people saying if it wasn't modified then its not an issue. That's irrelevant. It could be they collected a novel, and lethal, wild variant. If that was released, the effect is the same.

So what does the CCP do? Well they aren't stupid. They know that the mostly likely scenario is a leak from the lab. Occam's Razon applies. So that's a PR disaster, internally and externally to China. So prevent any outside inspections. They will turn up, demand samples, take samples, test samples. If the virus is discovered in the lab you have a public relations problem. Note. It doesn't prove the lab as the origin as a researcher could have got the virus externally and brought it in. But the PR works the other way. So no inspections. Of course that means people conclude it came from the lab, and its being hidden. You also need an alternative. The under cooked bat idea. Problem here is there is no evidence of bats being sold in Wuhan, its the wrong time of year because they are hibernating. Photos of researchers collecting bat shit without protective gear in order to investigate corona virus infections in humans just shows how bad their bio security was.

On Tue, 12 May 2020 at 10:43, Gilles Demaneuf notifications@github.com wrote:

Thanks. I fully agree with 'the accidental' conclusion. One should not underestimate the possibilities of Murphy's law combined with sloppy practices.

If China has plan (like any major power I would suspect) to weaponize viruses, it would likely still be a few years down the line and most likely in another lab. So there is no real need to go there.

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angoffinet commented 4 years ago

I agree fully with your view, one small step after the other, finally leading to catastrophe. The remedy to this is external feedback. Scientists in the West are getting feedbacks from government agencies, from grant agencies, from colleagues. In China, it is different. CAS is omnipotent and does not even know what feedback could mean.

Nickleaton commented 4 years ago

Well on your conclusion about the west. If we take Ferguson from Imperial college as an example. He was instrumental in the initial phases in the UK Lets look at his track record, and this excludes his predictions on Foot and Mouth

We treat his predictions as an investment of £1 trillion pounds

Year Event Prediction Reality Value 2002 BSE 50,000 177 3,540,000,000 2005 Bird Flu 200,000,000 282 4,991.40 2009 Swine Flu 65,000 457 35.09 2020 Covid-19 510,000 30615 2.11

[The formatting might be a bit off]

You would have been left with £2.11, not enough for a cup of coffee.

So his predictions were disastrously wrong. The feed back mechanism was not present at all. He predicted disaster after disaster. What's happened is that his politics have been feed into his prediction in to manipulate policy. Pretty much the same sorts of errors in China. It also shows a complete lack of feedback.

I've had a look at the code, its a disaster. No regression tests for starters. Quality assurance is completely missing. The idea of what they were trying to do was, I think correct, You do need a stochastic model because its the super spreaders [ie. Politicians, Doctors, travellers], that are the key to getting the virus under control. A simple diferential equation model is not sufficient to ask policy questions as to what works or doesn't. The implementation is so flawed however as to be useless.

Even a post infection model, can't even predict actual deaths for example for Sweden, where there is a policy difference.

On Tue, 12 May 2020 at 11:10, Andre Goffinet notifications@github.com wrote:

I agree fully with your view, one small step after the other, finally leading to catastrophe. The remedy to this is external feedback. Scientists in the West are getting feedbacks from government agencies, from grant agencies, from colleagues. In China, it is different. CAS is omnipotent and does not even know what feedback could mean.

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research-project-cov commented 4 years ago

angofinet, what do you make of this study? Is it scientifically sound?

https://medium.com/@yurideigin/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748

I can't comment on biology (I am not specialized), however, all what this report says on Yunnan and its geography, situation in Wuhan, knowledge of China and virus outbreak, is surprisingly very accurate, without mistakes.. it is a serious work. As an anecdote, this same Yuri Deigin made a paper years ago to expose Jeanne Calment 121 years old record (the daughter would have impersonated the mother for tax evasion)

nemonominem commented 4 years ago

angoffinet, may I ask your ideas on one point? I have been left wondering at the seemingless absurdity of going and collecting 1,500 coronavirus from Southern China bat caves with limited protections (P2 or less?).

Here are two questions for you:

I am asking this because I cannot stop thinking that based on available information at the time, which itself must have been based on at most 100 or so collected coronaviruses so far, maybe the impression in China was that there was no real danger - no real risk of contagion to human. Or at least no accident observed so far.. It's the usual black swan problem. There is no black swan until you see one, which over 1,000 swans becomes likely even if the individual probability is only around 0.1%.

I remember the batwoman saying that she was stupefied to find out so many coronaviruses in these caves. But I never read about her team taking increased protections faced with an increasing probability of a tail event (finding a black swan). So I just wonder whether it could be be one of these one step-at-a-time descent into a high risk zone with eyes-wide-shut.

angoffinet commented 4 years ago

I think exactly along the same lines. People have been in contact with bats in caves in all south east asian countries. They even use this as tourist attractions and my wife and I went to see that in Burma (Hpa-An) in ... januray 2020, even getting some bat excrements on our heads. They also collect bat guano in caves as fertilizer. In Yunnan, they make so called Poer tea, and leaves are fermented in caves where there are lots of bats. Some workers get occasionally infected from those bats, and I read some even died, but the disease never spread from human to human. Bat collectors know there are risks. There is for example Tian Jun-Hua and his crazy video:

https://www.youtube.com/watch?v=gYOetKA1o4U&fbclid=IwAR333npF8RTVol4QkNhsIkEAB5o5K59AnALD1JKGZSz1mpAJrGTdSHuKIM8

But they underestimated the risk. Also, they did not just collect corona and other viruses, but they put them in culture on various cell types, they modified them genetically , injected them to various animals, to investigate the mechanisms by which viruses can adapt to humans. So, yes, you are right. It is obvious to me that Zhengli Shi and her colleagues are decent scientists and aimed nothing wrong. But in RETROSPECT, we see that such behaviour was and is irresponsible. Things need to be investigated without hatred to learn what happened in order to regulate virus collecting and GOF experiments in the future, all over the world and not only in China. I placed my discussions on a blog: blogoncovid.blogspot.com

angoffinet commented 4 years ago

I read this and passed it around to some colleagues. We found no flaws and what is said seems correct. The virus RNA manipulations as indicated are doable and with modern technology, leave no "trace" of engineering.

Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le mer. 13 mai 2020 à 09:58, anonymous notifications@github.com a écrit :

angofinet, what do you make of this study? Is it scientifically sound?

https://medium.com/@yurideigin/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748

I can't comment on biology (I am not specialized), however, all what this report says on Yunnan and its geography, situation in Wuhan, knowledge of China and virus outbreak, is surprisingly very accurate, without mistakes.. it is a serious work. As an anecdote, this same Yuri Deigin made a paper years ago to expose Jeanne Calment 121 years old record (the daughter would have impersonated the mother for tax evasion)

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research-project-cov commented 4 years ago

what about this? it seems to me some are trying to dilute the deductions: more and more Yunnan bats;.. Or expert debate? "A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein" https://www.sciencedirect.com/science/article/pii/S096098222030662X#! and "HIV-1 did not contribute to the 2019-nCoV genome" https://www.tandfonline.com/doi/full/10.1080/22221751.2020.1727299?utm_source=CPB&utm_medium=cms&utm_campaign=JPA12926

angoffinet commented 4 years ago

Sadly, many journals are eager to publish on the coronavirus because it is fashionable and will increase their impact factor. In "normal" times, most of those papers would be rejected for lack of interest. I don't think those papers have much value (I am not saying they are incorrect). It may be best to ignore them.

research-project-cov commented 4 years ago

sorry to ask, but would it be possible that RatG13 does not exist, and that the sequence has been made-up using an old expedition in Pu'er city in Yunnan ? would it be a plausible explanation, or is it too improbable?

angoffinet commented 4 years ago

I do not know and honestly I am not eager to dig into it. We do not have access to full data and are not professional detectives. Based on data available on "project evidence" , plus analyzes by some colleagues, there is ample evidence for extensive GOF experiments in Wuhan and for a plausible leak. This is more than enough to request an investigation and call for an international moratorium on GOF experiments. Whether common sense will be heard is a political matter that unfortunately reaches beyond what we can do.

angoffinet commented 4 years ago

I just read this about RatG13 , which is deeply troubling. I am not familiar enough with virus sequences to appreciate arguments critically.

https://nerdhaspower.weebly.com/ratg13-is-fake.html Would anyone at Project-Evidence look carefully and feedback on this important question?

Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le sam. 16 mai 2020 à 01:03, anonymous notifications@github.com a écrit :

sorry to ask, but would it be possible that RatG13 does not exist, and that the sequence has been made-up using an old expedition in Pu'er city in Yunnan ? would it be a plausible explanation, or is it too improbable?

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nemonominem commented 4 years ago

angoffinet, you may appreciate that paper written by Yuan Zhiming, the Wuhan Institute of Virology’s Communist Party chief. On the 20th April 2020 he hit back at those promoting theories that the virus had escaped from the Wuhan P4 facility. “There is absolutely no way that the virus originated from our institute,” Yuan said in an interview with the state-run China Global Television Network.

In September 2019 Yuan Zhiming published a detailed paper in the Journal of Biosafety and Biosecurity that listed many operational and financial issues with Chinese labs. Here are a few chosen quotes:

"[...] due to different investment sources, affiliations, and management systems, the implementation of these laboratories faces difficulties converging objectives and cooperation workflows. This scenario puts laboratory biosafety at risk since the implementation efficiency and timely operations are relatively compromised."

"[...] several high-level BSLs have insufficient operational funds for routine yet vital processes. Due to the limited resources, some BSL-3 laboratories run on extremely minimal operational costs or in some cases none at all."

"Currently, most laboratories lack specialized biosafety managers and engineers. In such facilities, some of the skilled staff is composed by part-time researchers. This makes it difficult to identify and mitigate potential safety hazards in facility and equipment operation early enough"

https://www.sciencedirect.com/science/article/pii/S2588933819300391

angoffinet commented 4 years ago

Thank you. Even if indirect, this is very interesting evidence that a leak is plausible and worth investigating.

research-project-cov commented 4 years ago

I come back regarding RatG13; Peter Daszak recently told The Sunday Times that RaBtCoV/4991 (found in Pu'er mine , Yunnan, 2013), had been renamed RaTG13. another track could be: could the transmission to human and transfer to Wuhan have dated from that 2013 virus sample campaign, and the virus mutated in 6 years to become SARS COV 2?

https://www.independent.co.uk/news/health/coronavirus-wuhan-institute-virology-bats-research-sars-a9601951.html

angoffinet commented 4 years ago

From what is discussed on twitter, especially by Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le dim. 5 juil. 2020 à 10:38, anonymous notifications@github.com a écrit :

I come back regarding RatG13; Peter Daszak recently told The Sunday Times that RaBtCoV/4991 (found in Pu'er mine , Yunnan, 2013), had been renamed RaTG13. another track could be: could the transmission to human and transfer to Wuhan have dated from that 2013 virus sample campaign, and the virus mutated in 6 years to become SARS COV 2?

https://www.independent.co.uk/news/health/coronavirus-wuhan-institute-virology-bats-research-sars-a9601951.html

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angoffinet commented 4 years ago

From what is discussed on twitter by some who went quite deep in this, it seems indeed that they are one and the same virus. 4991 would be a partial RT-seq, about RdRp in particular. RATG would be the whole viral genome, assembled with reads in 2017 and 2018, final assembly prior to Nature paper (Pen Zhou first author) early this year. RATG13 is a computer construct and the virus was never available as such and has apparently not been constructed yet. All this is extremely strange and puzzling. Daszak is heavily involved in the cover up. He has a conflict of interest,like authors of the Andersen et al Nat med paper. Nothing that they say or write about SARS2-related items can be believed, at least not without checking other independent sources. If you wish, I can try and fish some more information. It is a bit difficult because dispersed in so many messages. Take care Andre Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le dim. 5 juil. 2020 à 10:38, anonymous notifications@github.com a écrit :

I come back regarding RatG13; Peter Daszak recently told The Sunday Times that RaBtCoV/4991 (found in Pu'er mine , Yunnan, 2013), had been renamed RaTG13. another track could be: could the transmission to human and transfer to Wuhan have dated from that 2013 virus sample campaign, and the virus mutated in 6 years to become SARS COV 2?

https://www.independent.co.uk/news/health/coronavirus-wuhan-institute-virology-bats-research-sars-a9601951.html

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angoffinet commented 4 years ago

Did you see this one? https://www.thetimes.co.uk/article/seven-year-covid-trail-revealed-l5vxt7jqp

Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le dim. 5 juil. 2020 à 10:38, anonymous notifications@github.com a écrit :

I come back regarding RatG13; Peter Daszak recently told The Sunday Times that RaBtCoV/4991 (found in Pu'er mine , Yunnan, 2013), had been renamed RaTG13. another track could be: could the transmission to human and transfer to Wuhan have dated from that 2013 virus sample campaign, and the virus mutated in 6 years to become SARS COV 2?

https://www.independent.co.uk/news/health/coronavirus-wuhan-institute-virology-bats-research-sars-a9601951.html

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research-project-cov commented 4 years ago

If you wish, I can try and fish some more information. It is a bit difficult because dispersed in so many messages. > .

many thanks; I think it is worth to get more information; I believe this is key to understand; it could explain also why professor Shi found so quikly that RatG13 is close to SARS-COV-2? I think serious reporters are also on the subject , as RatG13 / 4991 stories starts to appear in the press

angoffinet commented 4 years ago

Some informations here, but you probably already know this publication: https://medium.com/@yurideigin/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748

The rest is dispersed in twitter and you can look using keywords such as

RATG13

With a few others, we would like to draft all this together, but it is difficult, a lot of work, and we know the conclusion will be always the same, namely that we need an official investigation about the origin of SARS2 in Wuhan. Thus, sometimes, I feel like loosing my time. All the best Andre Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le dim. 5 juil. 2020 à 17:10, anonymous notifications@github.com a écrit :

If you wish, I can try and fish some more information. It is a bit difficult because dispersed in so many messages. > .

many thanks; I think it is worth to get more information; I believe this is key to understand; it could explain also why professor Shi found so quikly that RatG13 is close to SARS-COV-2? I think serious reporters are also on the subject , as RatG13 / 4991 stories starts to appear in the press

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nemonominem commented 4 years ago

Andre,

I believe that we should also follow a probabilistic approach. We can start bracketing some probabilities and do some (Bayesian) updates of these as we refine them. The good thing is that the approach actually shows that under a wide range of very conservative probabilities, the zoonotic hypothesis has very low likelihood.

I did a quick sketch, and to get to a 50% zoonotic/non-zoonotic balance one would have to suppose biosafety levels that simply do not exist in this world.

It would be interesting to see what ranges experts give to each underlying probability, but I am fairly confident that the result does not change. One advantage also is that it shows the unacceptable risk that is generally currently being taken in China with all these P3/P4 being built.

Here is my quick sketch. Please let me know what you think (I did not use a Bayes formulation, the approach below is simpler and easier to read):

===== The key question that we are all interested in is: 'Has the Wuhan virus outbreak anything to do with coronavirus research activities in Wuhan (be it accident at collection, transport or during lab handling or lab activities involving a coronavirus)?'

If it has nothing to do with these activities, then is is a pure random zoonotic event, if it has to do with such activities then China has a huge responsibility.

It is actually not difficult to bracket some probabilities:

Natural transmission to human of a coronavirus can be expected to happen in China roughly every 10 year. The Chinese are well aware of this risk, that is indeed the basic reason why they have been working so hard to study these viruses. Now the outbreak started in Wuhan and crucially nowhere else. Wuhan has 1% of China's population, so based on population proportion the chance of such a zoonotic outbreak to happen precisely in Wuhan (against somewhere else in China) is 1%.

However there is a big problem with that: Wuhan has no natural reservoir of bat population. None at all. So maybe it is due to bats being transported to markets, right? But then why only Wuhan? The bats from the same populations would have been transported to other cities too. Not only that but it is now proven that many of the early infection cases had nothing to do with any market, and that the market itself was not selling any bat.

So let's be very generous and say that this logical impossibility only halves the probability of a zoonotic event in Wuhan (against happening somewhere else in China). That gives us the probability of a zoonotic event exclusively in Wuhan at 0.5% in 10 years.

First there is the probability of an accident during collection of the viruses in South China caves. It has been widely reported that such collection was uphazard, with people being shat on or bitten by bats for instance. Over 10 years they collected at least 1,500 viruses for further study in Wuhan. Even if you put the risk of contagion per virus at a very low 0.01% (1/10,000 - quite generous!) , over 1,500 viruses you get a 15% chance of an accident over 10 years.

Secondly there is the probability of accident during transport to Wuhan where these viruses were near exclusively being studied. We know nothing about these transport conditions. So very generously I shall put that probability at 0% when it certainly is not null.

Last there is the probability of a leak in the lab of a collected virus, and the probability of a leak of a virus created through Gain of Function (GOF) experiments (which are very dangerous because they naturally select for the most contagious viruses). A lot of nonsense has be written here. People tend to mix everything up.

For instance some say that such event cannot happen because Covid 19 is not a synthetic virus. This is just wrong - we are talking of natural viruses collected in South China caves or naturally selected though GOF. These viruses are not synthetic.

Some say that the P4 lab cannot leak because it is P4. Again wrong. 3 or 4 labs were studying coronaviruses in Wuhan, most often at low P2 level, including the P4 lab itself!

Some say that Shi Zhengli clearly stated that covid-19 was not matched by any coronaviruses in the P4 gene bank, proving that it cannot come from Wuhan. Again wrong. The CDC P2 lab in Wuhan holds 450 coronaviruses for instance and they never told us if covid-19 matches any of theirs. Also many new viruses were coming into Wuhan all the time and we can be pretty sure that the latest batches were not yet sequenced (actually one of the main projects involving Wuhan and Singapore was the mass-sequencing of coronaviruses to be able to deal with the sheer quantity of viruses). And that's before considering that she may just be lying and that facts are better than words.

Actually the best insight into the real risk of lab leakage is provided by nobody else than Yuan Zhiming - the most senior CCP member of the Wuhan P4 lab (and a top scientist there) - who in Sep 2019 published an article in the Journal of Biosecurity and Biosafety that highlighted big structural issues in Chinese labs (including lack of funding, lack of training, lack of standard operating procedures, see https://www.sciencedirect.com/science/article/pii/S2588933819300391?dgcid=rss_sd_all).

This is not conspiracy theory. Accidents can and do happen. For instance there were at least 6 SARS lab leakages in the world since 2003, including 4 in China. See https://www.vox.com/future-perfect/2019/3/20/18260669/deadly-pathogens-escape-lab-smallpox-bird-flu

Add to that the problem highlighted by Yuan Zhiming and we are talking about a real risk. Based on similar risks in the world, the number of labs in Wuhan, precedent accidents in Beijing, the massive number of coronaviruses being handled, the fact that coronaviruses were often studied only at P2, it is quite generous to put the probability of a coronavirus lab accident in Wuhan at 1 over 10 years.

No let's sum the probabilities of collection, transport and lab: 15% + 0% + 100% = 115%, so 1.15 event every 10 years, which I will generously reduce to 1 over 10 years.

Zoonotic event in Wuhan and nowhere else: 0.5% over 10 years Non-zoonotic event in Wuhan (and nowhere else - which is easy as Wuhan has at least 90% of coronaviruses stocks and studies in China): 100% over 10 years.

So if you repeat the experiment 200 times you get 1 zoonotic events and 200 non-zoonotic ones. Hence if you observe one event in Wuhan (and nowhere else), the probability of it being non-accidental is 200/201 = 99.5% Yes basically certainty!

Now you can play as much as you want with the probabilities, but you will not find even a remotely convincing set of probabilities that brings that result to 50% (while the Chinese are insisting that it is near 0%).

Just to get to 50% you would have to suppose biosafety levels that exist nowhere in the world, across the full chain (collection, transport and lab) when everything, including the Chinese themselves, is quite frankly telling us that this is not the case.

research-project-cov commented 4 years ago

many thanks for this probability evaluation I myself has been a student in a chinese science institute in early 90ies (not wuhan!); I was reported governance problems at WIV: jealousy for a part (2018 appointment of 37 years old Wang Yanyi as director, for instance); willful misconduct could also be considered. it would be also interesting to have the hazop report of the P2, P3 and P4 (french Merieux, RTV should have the P4's) and evaluate the risk of multiplication of these labs (whereas risks are analysed per lab not considering others).

last, china tries to claim the origin of SARS COV2 comes from outside china (zoonotic or not); what would be this probability?

nemonominem commented 4 years ago

Well, we can always try to bracket the probability of even the wildest theory, so let's give it a go. First we need to clarify the hypothesis here, which is not very easy as the Chinese narrative changed quite a lot. I believe that it can be summarized as 'Covid19 originated in Fort Derek and was brought to Wuhan by US participants during the Wuhan military games'. OK, let's go with that.

Let's look at the story origin and the supposed source and chain of contamination.

2) Other alternative: malevolent contamination. Sorry but that is pure conspiracy theory, and it makes no sense whatsoever given the US lack of preparation.

So putting things together:

Which gives 1/160 of 1 event in 10 year chance of an accidental accident in a given US lab handling coronaviruses at BSL 3 (Fort Derek), with an accidental contamination chain from that lab accident to the Wuhan known cases, going through the Wuhan games, and no known case anywhere else.

Basically it does not even register against the reasonable 1 event in 10 year chance of a coronavirus lab accident in Wuhan.

By the way it does not matter what the source outbreak probabilities are in this argument. Let's be generous and say that the probabilities are the same in a Chinese or a US lab (let's call it p). At the end of the day there were at least two labs handling coronaviruses in Wuhan, and they don't need a weird exclusively directed chain as the Fort Derek hypothesis. So we are comparing 2 x p for the Wuhan leak hypothesis against 1 x p x 1/20 x 1/2. There is a ratio of 80 between the two! Let's be very generous and say that the lack of a known chain linking the Wuhan games to the Wuhan outbreak does not deserve a 1/2 (you can trust that the chinese would have likely found that chain if it existed though!) and you still have a 40 ratio.

At 40 the stats give you 97.5% chance of a Chinese lab leak against 2.5% chance of a Fort Derek leak given what was observed (outbreak in Wuhan and nowhere else). An that is starting with a generous equivalence of risk at source which does not make much sense.

angoffinet commented 4 years ago

I also heard about personal and politics being involved in WIV, with young director being the wife of a prominent immunologist in Wuhan, etc... But I do not think there has been any intentional michief, just some sloppy pratice, Hanlon's razor kind of.

Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le dim. 5 juil. 2020 à 23:46, anonymous notifications@github.com a écrit :

many thanks for this probability evaluation I myself has been a student in a chinese science institute in early 90ies (not wuhan!); I was reported governance problems at WIV: jealousy for a part (2018 appointment of 37 years old Wang Yanyi as director, for instance); willful misconduct could also be considered. it would be also interesting to have the hazop report of the P2, P3 and P4 (french Merieux, RTV should have the P4's) and evaluate the risk of multiplication of these labs (whereas risks are analysed per lab not considering others).

last, china tries to claim the origin of SARS COV2 comes from outside china (zoonotic or not); what would be this probability?

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angoffinet commented 4 years ago

Claiming it originated outside China is pretty pathetic. They blamed USA and military games, sounding quite ridiculous to say the least. A few weeks ago, they hinted that the origin may be in Italy, where bats (pipistrella) have been hosted in cities to fight mosquitoes (which is true, but no coronavirus in those bats as far as we know). The chinese narrative is incredible all along and reads more like panic-driven than anything plausible. Not sure that bayesian analysis can help much when dealing with low odds like this. But it is worth trying, and an elegant and useful case study.

Andre GOFFINET, MD, PhD Prof. em. Institute of Neuroscience University of Louvain, Belgium +32 (0) 473 899818

Le lun. 6 juil. 2020 à 03:35, Gilles Demaneuf notifications@github.com a écrit :

Well, we can always try to bracket the probability of even the wildest theory, so let's give it a go. Firs t we need to clarify the hypothesis here, which is not very easy as the Chinese narative changed quite a lot. I believe that it can be summarized as 'Covid19 was brought to Wuhan by US participants during the Wuhan military games'. OK, let's go with that.

Let's look at the story origin and the supposed source and chain of contamination.

-

First there is a big problem with the chain: China has never even hinted to a known link between a Wuhan infection and someone attending the Games. No that's surprising. You would suspect that by now they would have been able to find a chain of contamination going back there. But no. None. It's a black hole - there is no known chain. That in itself knocks the theory back by a few orders. (The opposite would be true: if the early chains of infections were pointing to the Wuhan game then the probability would be high that the hypothesis is valid).

Then there are the contradictions in the story. We were told that some athletes were treated for covid like symptoms in an hospital in China, when the same hospital later clarified they were treated for malaria. Then we were given the name of a US athlete (which was first floated by a US based conspiracy theorist). Again all hot air - that athlete did not have covid. Does not make it very realistic.

Then we can look at the supposed source. There there are two alternatives: accidental contamination in the US of a/some participant(s) and malevolent contamination.

  1. Accidental contamination. The problem is that there are no Souther Chinese bat populations in the US as you can imagine. So it would have to be accidental contamination at a lab. Great. But wait a second, between the probability of an accidental contamination in a US lab and the probability of an accidental contamination in a Wuhan lab, which one do you think is the highest given the security infrastructure and the number of covid projects worked on? I would say the probability of a covid lab accident in the US (if not the whole rest of the world) is at most 1/4th the probability of the same lab accident in Wuhan. But that's not all. Because we are talking about a US covid 19 accident with no known cases in the US and only knows cases in Wuhan. So you could look at something like the total population of the major cities around US lab against the Wuhan population and also multiply that ratio with something like 1/10 for the chance that a lab employee (or someone close to an asymptomatic lab employee) went to Wuhan as part of the US delegation. At the end of the day you will get something like 1/4 x 1/2 x 1/10 = 1/80. Other alternative: malevolent contamination. Sorry but that is pure conspiracy theory, and it makes no sense whatsoever given the US lack of preparation.

So putting things together:

  • source: x1/80 * 1 event every 10 years
  • chain: maybe x1/2 (due to its weakness - no known)
  • story fuzziness: I will be generous and not reduce the probabilities
  • so x1

Wich gives 1/160 of 1 event in 10 year chance of an accidental accident in a US lab, with an accidental contamination chain from that lab accident to the Wuhan known cases, going through the Wuhan games.

Basically it does not even register against the reasonable 1 event in 10 year chance of a coronavirus lab accident in Wuhan.

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nemonominem commented 4 years ago

I agree that it is odd. But to be fair if one believes in Bayesian analysis then one should still give it a go. The beauty about this anyway is whatever range you give to each probability, there is no way that the US virus hypothesis even registers against the lab accident or the zoonotic event. If someone tells me that they still believe in it, then I just ask them to give me their probability estimates that are consistent with their conclusion. They can't - as simple as that.

The same goes with the zoonotic hypothesis. The fact that the outbreak started in Wuhan, and only in Wuhan, knocks that one back about 2 orders against the lab accident.

Both the 4 previous SARS lab release in Chinese lab and the very honest warning (should I call it red-flag waving?) from Yuan Zhiming show that lab accident probabilities are at least (to be very generous) as likely in Wuhan than in the rest of the world. If you consider the number of viruses, projects, labs involved in Wuhan then that risk becomes insolently high.

This is my second conclusion Andre: not only probabilities show us that most likely covid-19 was a lab accident, but the probability of another lab accident of the same sort over the next 10 years is just as high, if not higher as more P3 and P4 are being built.

We need to get this message out, backed by a probability analysis. This is endangering us all.