ice9 Profile picture
16 Sep, 37 tweets, 31 min read
@phl43 @YmeKindsome @antihero_kate You make several claims:

1) that more possible routes somehow weigh against a hypothesis about an event-- the opposite is true

2) that lack of certainty of details means 'confusion' and reduces credibility-- rather, excessive certainty does

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@phl43 @YmeKindsome @antihero_kate ...

3) that CCP suppression of early data is a mere 'narrative' and 'mostly nonsense' -- everyone remembers Li Wenliang

4) I am not advocating for the postdoc theory-- I already looked into this months ago and the publication record shows departure years earlier

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@phl43 @YmeKindsome @antihero_kate ...

5) "Research on the cross-species infection and pathogenicity of bat viruses" this is literally directly related to the southern Chinese bat CoV hACE2 survey grant I continue to link, which you continue to ignore



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@phl43 @YmeKindsome @antihero_kate ...

6) more stuff about a grad student I never mentioned and consider obviously uninvolved

7) nothing whatsoever in my argument is based on Chinese social media rumors or similar, but rather entirely on papers, manuscripts, and I suppose maps

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@phl43 @YmeKindsome @antihero_kate ...

8) if a researcher was infected, it would have likely been a mild case, but either way it is irrelevant whether or not the first infected individuals died

9) I agree: the distinction between infection by a stored undisclosed natural strain vs. recombinant is irrelevant

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@phl43 @YmeKindsome @antihero_kate ...

10) I have never seen the website you mention

11) I have said nothing about animal escape, which seems if anything less likely than an unnoticed accidental human infection given long contagious incubation period

12) again you claim diversity of arguments is a weakness

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@phl43 @YmeKindsome @antihero_kate ...

13) the pangolin theory was discredited by a team at the Broad Institute, some of whom now openly believe a lab accident was more likely



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@phl43 @YmeKindsome @antihero_kate ...

14) "Of course, this is just one possibility, but the actual story could be even more complicated" contingency for me but not for thee

15) more stuff about discredited pangolin theories; it's a bat CoV or close to one

16) artificial chimeras are mentioned in the grant

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@phl43 @YmeKindsome @antihero_kate ...

17) "scientists could have replaced the RBD of a bat coronavirus related to RaTG13-CoV... which might have given rise to SARS-CoV-2 either directly or after enough rounds of simulated evolution" they literally wrote about doing this

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@phl43 @YmeKindsome @antihero_kate ...

18) "Again, this is certainly possible, but lots of things are possible and most of them never happened" usually the ones declared in grant proposals do actually happen, otherwise it is called fraud

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@phl43 @YmeKindsome @antihero_kate ...

19) "If you want to blame China" something similar could have just as easily happened in another country-- the original H5N1 ferret gain-of-function study was done in the west, and the U.S. moratorium on gain-of-function work had expired. China merely discloses less.

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@phl43 @YmeKindsome @antihero_kate ...

20) "I don’t think it’s evidence the virus was bioengineered in a lab except in such a weak sense that it’s totally uninteresting"

it *is* interesting-- not because it shows malice (it does not), but because it matches an ongoing animal infection project and dN/dS data

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@phl43 @YmeKindsome @antihero_kate ...

21) "it raises the probability that SARS-CoV-2 was bioengineered at the WIV somewhat, but the fact that I’m a man also raises the probability that I’m a serial killer (since they are more often male)"

A better analogy: being the only known male within 1900 km

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@phl43 @YmeKindsome @antihero_kate ...

22) "bat coronaviruses are massively undersampled," I agree, but bat coronaviruses are carried by bats-- which hibernate or migrate in winter. Wuhan is not even within the northern or southern ranges of horseshoe bats, and SARS-CoV-2 solely resembles southern strains.

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@phl43 @YmeKindsome @antihero_kate ...

I will note again that the grant above specifically focused on southern Chinese bat CoVs, which are not native to the region of Wuhan itself.

23) you continue to assume all sampled strains are disclosed, which makes no sense given the scope of the survey project

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@phl43 @YmeKindsome @antihero_kate ...

24) "However, had they used RaTG13-CoV as a backbone and simulated natural selection to create SARS-CoV-2 in that way, there would be signs in the genome of the virus that it had recently been under strong selection" I agree, which is why the recombinant study fits best

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@phl43 @YmeKindsome @antihero_kate ...

25) "they almost certainly didn’t use RaTG13-CoV but another bat coronavirus nobody except them knows about. I guess it’s possible, but there is no reason to think it ever happened."

Again, except for a grant describing doing exactly this.

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@phl43 @YmeKindsome @antihero_kate ...

26) "If researchers at the WIV had been doing that kind of experiments, it’s surprising that no scientists elsewhere had heard about it through the grapevine"

grantome.com/grant/NIH/R01-…

This describes a large ongoing project with new samples and synthetic methods.

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@phl43 @YmeKindsome @antihero_kate ...

27) "Only someone who is already committed to the lab escape theory would have a reason to make this hypothesis, because otherwise this version of the theory is untenable"

I became most concerned about it when I saw these papers and then this grant, actually.

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@phl43 @YmeKindsome @antihero_kate ...

28) "But there was no reason to think this RBD should have been good at binding human ACE2 and, on the contrary, structural analyses would apparently have predicted it wasn’t optimal at doing so." The grant discusses direct in vitro assays to find RBDs that bind hACE2.

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@phl43 @YmeKindsome @antihero_kate ...

29) after this, you make more arguments centered on WIV dutifully uploading all of its sequences to public databases, which is ridiculous given they didn't even upload the ones from the infected miners years ago

independentsciencenews.org/commentaries/a…

see translated thesis here.

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@phl43 @YmeKindsome @antihero_kate ...

30) "The same thing can be said about the version of the lab escape theory according to which SARS-CoV-2 evolved naturally, but ended up in a lab where it was studied by scientists and from which it accidentally escaped" that does not need sequencing, only mishandling

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@phl43 @YmeKindsome @antihero_kate ...

31) "we can’t rule this possibility out (... viruses have escaped from labs before), but we also have no reason to think it actually happened." Except for being the only known source of extremely closely related viruses within 1900 km, and actively infecting animals

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@phl43 @YmeKindsome @antihero_kate ...

32) "We’d have to assume that scientists at the WIV had discovered... another, closely related virus that somehow infected someone at the lab or in the vicinity, circulated in humans"

That literally happened, ironically, but it is not required.

independentsciencenews.org/commentaries/a…

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@phl43 @YmeKindsome @antihero_kate ...

33) "she could be lying, but there is no evidence whatsoever that she is"

There are many ways to "not find" something, if finding it could mean complete personal and institutional destruction.

China has handed down death sentences for mere chemical accidents.

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@phl43 @YmeKindsome @antihero_kate ...

34) yes, there were known safety issues at WIV, but that isn't even the point-- SARS-CoV-2 is highly transmissible, including though aerosols, and there are many documented instances of workers in BSL3/4 labs in many countries being inadvertently infected by pathogens

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@phl43 @YmeKindsome @antihero_kate ...

35) "this passage is more naturally interpreted as saying that the work in question was important to prevent the emergence of another coronavirus that can transmit to humans"

this has always been the fig leaf for gain-of-function work



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@phl43 @YmeKindsome @antihero_kate ...

36) "the controversial experiment was performed at the University of North Carolina, not the WIV" in 2015, by people who left for China when the U.S. imposed a moratorium on gain-of-function research funding, including e.g. Zheng-Li Shi.

nature.com/articles/nm.39…

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@phl43 @YmeKindsome @antihero_kate WIV opened its nominally BSL4 lab in... 2015, interestingly enough. Just in time to absorb those researchers.

en.wikipedia.org/wiki/Wuhan_Ins…

It is one of the world's foremost research facilities on Chinese bat CoVs.

english.whiov.cas.cn/About_Us2016/H…
@phl43 @YmeKindsome @antihero_kate ...

37) you note the Wuhan Center for Disease Control and Prevention is located only a few hundred meters from the Huanan market-- this is very interesting, as it provides further reason for WIV staff to visit the area

38) I am not proposing a particular stochastic model

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@phl43 @YmeKindsome @antihero_kate ...

39) here is yours:

P(W|!L) = miniscule, bats uncommon, winter, far from known similar CoV sites, <1% PRC population

P(W|L) > 50%, main SARS-like CoV lab

P(L) = suspected in a few past events, subject of active GoF research, maybe 5%

P(!L) = 95%

Left is smaller.

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@phl43 @YmeKindsome @antihero_kate ...

Note I interpreted some of the events a bit differently. I say 'lab' if it starts from a lab anywhere in China. I say 'not lab' otherwise. I say 'Wuhan' if it starts in Wuhan, 'not Wuhan' if it were to hypothetically start in another city instead.

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@phl43 @YmeKindsome @antihero_kate ...

Given the wide range of different results obtained from this model, I would argue that it is rather useless in this form for drawing a conclusion in its own right-- serving more as a mere sanity check for a hypothesis.

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@phl43 @YmeKindsome @antihero_kate "shouldn’t fool ourselves into thinking that we’re going to prove or... refute that SARS-CoV-2 escaped from a lab with this kind of mathematical tricks."

Agreed.

"have the appearance of rigor, but they are really tools of persuasion"

Disagree, tool for double-checking.
@phl43 @YmeKindsome @antihero_kate Finally, you note nearly all natural bat CoVs are terrible at spreading in humans.

This is largely due to poor ACE2 affinity, absence of furin site, etc.

The obvious conclusion is that optimizing hACE2 binding as the grant describes makes it more likely to have been artificial.
@phl43 @YmeKindsome @antihero_kate I do not expect you to bother updating for new evidence or to even read any of this. I will be surprised if you do.

I wrote this to check for myself-- as to whether there is anything important that I might be missing, as you seemed very convinced above.
@phl43 @YmeKindsome @antihero_kate I conclude there is not, or at least not in this essay. You are simply missing key evidence-- the same evidence that caused me to reconsider my earlier view, which was previously more similar to yours.

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More from @__ice9

26 Sep
Depletion of surfactant from the lungs of rats followed by mechanical ventilation is sufficient to cause infiltration by neutrophils, tissue damage, and pneumocyte apoptosis.

COX-2 expression was reduced, and treatment with COX-2 inhibitors further worsened the resulting damage.
Histological samples resemble autopsies from fatal COVID-19, with extensive alveolar exudates, epithelial cell apoptosis, and neutrophil infiltration.

SARS-CoV-2 destroys secretory cells, reducing surfactant production and thereby promoting the above. Replace the surfactant.
COX-2 inhibitors further increased the damage. Most aren't used often anymore, as they were infamously associated with cardiovascular disease.

The reason is likely their mitochondrial toxicity, especially harmful under conditions of intense stress.

sciencedirect.com/science/articl…
Read 6 tweets
23 Sep
Interesting.

ncbi.nlm.nih.gov/pmc/articles/P…

Some references for the hypothesis that post-acute COVID-19 might be partly an endocrine disorder.

Note treatment for Addison's disease is often corticosteroids as well.
Read 9 tweets
22 Sep
About 60 percent of severe COVID-19 patients in the ICU exhibit clinical symptoms that look essentially indistinguishable from serotonin syndrome.
This fits evidence provided earlier showing elevated plasma serotonin levels in COVID-19.

Consistent with observed platelet activation (platelets store most peripheral serotonin) and damage to pulmonary endothelium (clears it from plasma)

Cyproheptadine and famotidine have been noted as effective in the treatment of serotonin syndrome.

aafp.org/afp/2010/0501/…

ncbi.nlm.nih.gov/pmc/articles/P…

Famotidine performs well in trials for COVID-19. I do not see any for cyproheptadine, but it shows up in protocols regardless.
Read 4 tweets
22 Sep
@vikramml @RealVladivostok Stephen Chen is a sensationalist.

60°C for one hour is usually enough for roughly a 5-log reduction in PFU terms in CoVs (see my post above).

Hence, starting with >100,000 viral particles could still allow infecting cells afterward.
@vikramml @RealVladivostok Gross appearance need not be altered during thermal inactivation, which involves thermal denaturation of key proteins.

90°C for 10 minutes reliably inactivates CoVs, including SARS-CoV-2.
@vikramml @RealVladivostok I am unsure why the article even bothered mentioning that the Spike protein wiggles. All proteins wiggle.

Spike count varies. The D614G mutation increased it by roughly a factor of 5, increasing infectivity. It is now carried by the majority of SARS-CoV-2 samples.
Read 5 tweets
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Cerebrospinal fluid of patients experiencing significant COVID-19 neurological symptoms contains high levels of inflammatory cytokines, often for weeks afterward.

Little evidence for any viral material in CNS tissue based on CSF samples at least.

Occasional vascular damage.
Overall, consistent with the view that post-acute COVID-19 neurological symptoms are likely mediated in large part by persistent inflammatory processes.
Evidence for both neutralizing and autoimmune origins:

medrxiv.org/content/10.110…
High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

biorxiv.org/content/10.110…
Immunologically distinct responses occur in the CNS of COVID-19 patients
Read 5 tweets
18 Sep
... RaTG13 and other bat CoVs from the same deadly Yunnan cave fitting the stated inclusion rule for use in the hACE2-optimized recombination grant, SARS-CoV-2 indeed binding human ACE2 hundreds of times better than SARS-CoV, winter in a city outside known ranges of such bats,
... fully synthetic recombination techniques and full genome data already available, prior use of non-SARS-CoV backbones and a clear justification for doing so again, a demonstrated history of refusing to disclose sequences and lying about both culture work and deadly pathogens,
... ground zero a human superspreader event at a market down the highway from the WIV CAS office and a few hundred meters from the Wuhan CDCP, *right around a biosafety conference with staff from the BSL3/4 lab* known to be infecting animals at the time.

Image
Read 17 tweets

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