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Hibernation

Open Nickleaton opened this issue 4 years ago • 74 comments

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.

Nickleaton avatar May 04 '20 10:05 Nickleaton

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.

angoffinet avatar May 05 '20 08:05 angoffinet

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.

wisefish99 avatar May 06 '20 07:05 wisefish99

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.

angoffinet avatar May 06 '20 08:05 angoffinet

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 .

wisefish99 avatar May 06 '20 08:05 wisefish99

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.

angoffinet avatar May 06 '20 11:05 angoffinet

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 [email protected] 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 .

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Nickleaton avatar May 06 '20 12:05 Nickleaton

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.

wisefish99 avatar May 06 '20 13:05 wisefish99

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 [email protected] 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 .

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Nickleaton avatar May 06 '20 13:05 Nickleaton

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.

angoffinet avatar May 06 '20 13:05 angoffinet

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.

wisefish99 avatar May 06 '20 13:05 wisefish99

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 [email protected] 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

Nickleaton avatar May 06 '20 15:05 Nickleaton

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.

f-pound avatar May 08 '20 05:05 f-pound

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.

angoffinet avatar May 08 '20 05:05 angoffinet

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 avatar May 08 '20 12:05 f-pound

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

f-pound avatar May 08 '20 13:05 f-pound

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 [email protected] 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 avatar May 09 '20 06:05 angoffinet

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.

research-project-cov avatar May 09 '20 17:05 research-project-cov

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 [email protected] 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 [email protected] 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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Nickleaton avatar May 09 '20 17:05 Nickleaton

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. 2. 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.

angoffinet avatar May 09 '20 19:05 angoffinet

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

nemonominem avatar May 12 '20 00:05 nemonominem

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?).

angoffinet avatar May 12 '20 06:05 angoffinet

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.

nemonominem avatar May 12 '20 09:05 nemonominem

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 avatar May 12 '20 09:05 angoffinet

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

angoffinet avatar May 12 '20 09:05 angoffinet

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 [email protected] 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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Nickleaton avatar May 12 '20 10:05 Nickleaton

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.

angoffinet avatar May 12 '20 10:05 angoffinet

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 [email protected] 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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Nickleaton avatar May 12 '20 10:05 Nickleaton

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)

research-project-cov avatar May 13 '20 07:05 research-project-cov

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:

  • Did it make sense to collect the 1,500 viruses the way they did it ** prior to knowing about coviv19 **
  • ** Now that we know about covid19 **, would it make sense to go and collect another 1,500 viruses that very same way?

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.

nemonominem avatar May 13 '20 08:05 nemonominem

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 avatar May 13 '20 08:05 angoffinet