1. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2!
2 papers:
Humanā€“viral molecular mimicry
https://www.nature.com/articles/s41420-020-00321-y
Molecular Mimicry
https://link.springer.com/article/10.1007/s12026-020-09152-6 https://twitter.com/BillyBostickson/status/1316138150842966017
3. Springer Article https://twitter.com/BillyBostickson/status/1318825651374358529
4. Takeaway most significant quotes from Springer Article, burn this into your brain:
"Such a peptide commonality is unexpected and highly improbable from a mathematical point of view"
5. One image to explain it all!
7. A timely vindication for SĆørensen, Susrud & Dalgleish
Biovacc-19: A Candidate Vaccine for SARS-CoV-2 Developed from Analysis of its General Method of Action for Infectivity
https://www.cambridge.org/core/journals/qrb-discovery/article/biovacc19-a-candidate-vaccine-for-covid19-sarscov2-developed-from-analysis-of-its-general-method-of-action-for-infectivity/DBBC0FA6E3763B0067CAAD8F3363E527
Image: Nonhuman-like (NHL) sequences found in SARS-CoV-2 spike protein S1.
8. Visual Reference
Benchmarking evolutionary tinkering underlying humanā€“viral molecular mimicry shows multiple host pulmonaryā€“arterial peptides mimicked by SARS-CoV-2
https://www.nature.com/articles/s41420-020-00321-y
9. What kind of Mice?
Human Immune System Mice for Study of HIV-1 Infection of CNS
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00649/full
"Immunodeficient mice transplanted with human cell populations or tissues, also known as human immune system mice, have become important & versatile tools for in vivo study"
10. SARS-CoV-2, the autoimmune virus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598743/
confirmation of peptide findings + autoimmune factors
11. Useful Mouse Graphic from @RandFanshier https://dovepress.com/immunocompromised-and-immunocompetent-mouse-models-for-head-and-neck-s-peer-reviewed-fulltext-article-OTT)
showing different kinds of transgenic mouse experiments
@RandFanshier asks:
"was it given human umbilical cord stem cells as an embryo, or did it get human epithelial tissue implanted as a SCID mouse?
12. Did Experimental vaccine immuno-suppressed transgenic hAce2 Mice from WIV Lab ended up on the dinner plate for the "three squeaks" delicacy?
once when it is picked up!
once when it is dipped in sauce.!
once when it is eaten..!
https://twitter.com/sauwingso/status/1220045500570693632
13. Three Blind Mice
newly born mice (still hairless and barely able to open their eyes). It is typically served with some type of cold soy based sauce. The first squeak is when the mouse/rat is picked up with the chopsticks.
14. The second is when the mouse/rat is dipped into the sauce (temperature change causing the squeak). The third is when the mouse/rat is placed into your mouth (another temperature change).
Typically, they are very newborn and thus the bone structure is still fairly loose. Iā€™ve heard that these have been served wrapped in seaweed before, but that may be more rumored than anything else.
https://www.culinaryschools.org/blog/three-squeaks/
16. Baby Mice äø‰å±å„æ
Newborn mice (San Zhi Er) are eaten alive with chopsticks & served in a spicy sauce.
They are called ā€œ3 squeaks babiesā€ because they scream 3 times.
Chinese Baike Baidu scrubbed the page
https://baike.baidu.com/error.html?status=404&uri=/item/%E4%B8%89%E5%8F%AB%E8%8F%9C/3857789
Google Search shows it "item/äø‰å«čœ/3857789"
`19. Back to the Labs..and Mice (1)
Dr. Anony Mouse kindly provides some useful insights:
"Perhaps a glance at the ACE2 transgenic mouse paper would be nice:
https://ncbi.nlm.nih.gov/pmc/articles/PMC7241398/pdf/main.pdf
Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
20. Dr. Anony Mouse explains
Paper submitted for publication on March 12th
At the time of these experiments, a viral pandemic was raging in Wuhan during the 2 months from ā€œdiscoveryā€ of virus to this publication & all interactions with the outside world were completely closed off
21. Dr. Anony Mouse (3)
The HfH-ACE2 transgenic mouse was developed in this paper in 2016 from the Baric lab, which people have pointed to back in May, when questions started to arise about what was going on. https://ncbi.nlm.nih.gov/pmc/articles/PMC4801244/. SARS-like WIV1-CoV poised for human emergence
22. Dr. Anony Mouse (4)
Remember, no reference to the Mojang miners was made in this 2016 paper.
Looking at the Methods section of the 2020 transgenic ACE2 mouse paper, it states that this mouse was from ā€œRalph S Baric lab.ā€
23. Dr. Anony Mouse (5)
This mouse had to have been at the WIV prior to the pandemic, since everything in Wuhan was closed from January to March. Also, how did any research get done at the WIV at that time, during total lockdown?
24. Dr. Anony Mouse (6)
From the Methods section of the paper:

HFH4-hACE2 mice
25. Dr. Anony Mouse (7)
Those of us who do science for a living understand the sheer implausibility of performing these experiments, writing them up, and submitting for publication in a 7-8 week period from viral isolation to publication.
26. Dr. Anony Mouse (8)
Especially during a viral pandemic where the entire city was completely shut down and movement restricted.
Possible? Yes. Probable?
Iā€™ll leave that determination to the scientific community...
So what was really going on?
27. Dr. Anony Mouse (9)
What likely happened is that they took the ACE2 transgenic mouse from the Baric lab and gave it a human immune system. This could be done by crossing the ACE2 transgenic mice with a mouse model (rag-/rag-) without a functioning immune system.
28. Dr. Anony Mouse (10)
These animal crosses are all the rage in immunology.
By crossing various ā€œknock outā€ and ā€œknock inā€ mice, you get all sorts of interesting immune things to study.
Itā€™s big in cancer immunology right now.
29. WTF did they do to me?
30. A "mice little experiment" that our dear Dr. Anony Mouse would have done...
31. Dr. Anony Mouse explains (11)
What the researchers at WIV didnā€™t plan for, I guess, is that SARS-CoV Urbani MA15 mouse adapted viral strain they were using continued to mutate in the animal model during passage.....
32. Dr. Anony Mouse explains (12)
Even in the ACE2 transgenic experiments in the 2020 Cell paper, two mutations were found in S and nsp13 that led to brain tropism and death in a few of the mice, even with only one passage.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241398/
33. Dr. Mouse explains (13)
Serial passaging in the chimeric mice selected for an even better human adapted strain.
This became more & more important to the scientists, since the better human adapted the strain became, the more like a real human infection it became in the mice.
34. Dr. Mouse explains (14)
I am sure the ā€œdual useā€ potential of this sort of experiment did not escape the notice of the CCP, though it would have been true insanity to develop it in that direction.
35. Billy Talking Now
But then again, they did very similar experiments in a Peking military laboratory back in September, where they developed the infamous N501 mutation (6 passages in mice)
Similar to one currently plaguing GB
https://twitter.com/BillyBostickson/status/1339180437197877248
&
https://science.sciencemag.org/content/369/6511/1603
36. Back to Dr. Mouse

"Like Icarus flying too close to the sun, they could not stop themselves"

The researchers and the mice ;)
37. Dr. Mouse concludes (1)
It was only lethal in this very inbred, manipulated mouse strain. At least theoretically. Though a virus with human potential for transmission was being used (mouse adapted SARS Urbani) the possibilities were endless.
38. Dr. Mouse concludes (2)
The best laid plans of transgenic mice and men...
They could develop drugs to blunt the immune response. They could develop anti-virals.
They could design recombinant live attenuated coronavirus vaccines and rapidly test them in these mice.
39. Dr. Mouse concludes (3)

The end of coronavirus as a threat to humans was at hand, if the experiments could just be performed correctly.
40. Dr. Mouse concludes (4)
Itā€™s exactly what some of us would have done
They likely said screw the GOF ethics
The experiments were just too cool, the potential benefit to humanity too great, and the ego boost from the possible accolades too strong.
We scientists totally get it.
41. Billy Talking Now

But we all know what happened to Icarus, don't we?

There is old Baric looking on in horror as his dear Chinese Icarus plunges......... to our death!
42. Dr. Mouse concludes (5)
These are the experiments I think they were doing in Wuhan during the past 18-24 months when the darn thing escaped.
Who knows what happened?
I suspect a lab tech handling an infected mouse was infected despite all the precautions.
43. Dr. Mouse concludes (5)
Maybe animal waste wasnā€™t handled properly.
(Billy suspects they sold the lab mice)
A human adapted SARS strain, with wider tissue tropism, better ACE2 binding & better ability to shut off interferon production than SARS was produced, and it LEAKED..
44. A mice story, thanks to Dr. Anony Mouse.
45. Connections, connections - of mice and vaccines.
Of course this tragic mice story ties in well with DRASTIC research into "vaccines gone wrong" posted a while back on Twitter by @Rossana38510044 https://twitter.com/Rossana38510044/status/1312412241615097856
You can follow @BillyBostickson.
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