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1. 2021-01-04 09:00 Andrew Rambaut
   Just sent to Bob and me (plus Christian Drosten, Trevor and Guy Hoelzer). ```Gentlemen, It appears that the mutations in the spike protein that causes PCR failure for that part of the Taqpath assay will befound to have induced a PCR selection bias, and thus contributed to the spread of the virus without increasedpathogenicity.Specifically, there will be more false negatives in tests of people with any variant with new variation in the primer target sequences, especially the 8 variants Andrew reported in the spike protein coding region. The reported PCRprobe failure in the S gene assures biased transmission of the virus since testing results in self-quarantine. This seems necessarily so given the diagnostic interpretive algorithm in use with Taqpath, the '2 or greater"algorithm, any single probe failure due to mistargeting will increase the probability of a failed PCR test overall given the sum baseline rate of failure of both of the other two probes.See p 104. https://www.fda.gov/media/136112/downloadIt should be straightforward and therefore I propose modeling and simulation to calculate the expected rate of test escape and selection due to mutations in any of the primer sites to distinguish pathogenic variants from those being selected by testing bias.I expect the results will show that test kits will have to be updated to keep up with RNA virus evolution. Free free to and please send any related material or draft analyses for friendly-fire review. I'm also of course interested in any variation associated with severe COVID19 or long-haul COVID19.I encourage working immunogenicity predictions into analyses interpretive of genetic variants as well. We can ofcourse expect evolution away from the vaccine type and from the more immunogenic types, which likely will cause more severe COVID19 as well asevolution away from human aa sequences due to increased risk of pathogenic priming due to autoreactive antibody production. Given these vectors, a path ofSARS-CoV-2 evolution might be mapped.Please reply-all for the favor of broad illumination.Also, should any of you care to discuss SARS-CoV-2 evolution on Unbreaking Science, contactSincerely,James Lyons-WeilerPS Re: origins: Check out HKU-3-3 - it appears to have SARS-CoV-2 -like functional motifs, but was published in2005/ Baric downloaded it in 2008. Both the original report and his people thought it was SARS. See second report here HKU-3-3 is a SARS-CoV-2 precusor, at least from the perspective of the spike protein.http://ipaknowledge.org/covid-19-and-sars-cov-2-research.phpAlso available herehttps://www.researchgate.net/publication/340769150_Motif_Pathogenicity_Typing_SARS-CoV-2_Coronavirus_May_Contain_a_Unique_Likely_Pathogenic_Protein_Motif_Signature_Also_Found_in_a_Natural_Isolate_from_2005```
2. 2021-01-04 09:08 Robert F. Garry open
   First Alina et al. The main problem is that this is antiscience. Stop don't do it? Really dangerous and ill informed.Crawling to caves is not the best way to trap bats. They need to fly out at dusk and feed. Mist nets near the entranceare a "safe" and effective way to catch the animals. [shared file(s): image.png]
3. 2021-01-04 09:14 Robert F. Garry open
   JL-W makes an interesting hypothesis. However, PCR failures are prob not enough to account for whatever increased transmission is being seen, but potentially a factor. Modeling would probably be a good thing to do.
4. 2021-01-04 10:13 Kristian G. Andersen open
   Ehm, James looks like an idiot to me, but maybe I'm missing something :wink: . I assume none of these new origin articles actually present anything new? Just the same all speculation circulated -give me some _specific_ data or _specific_ testable hypotheses, and I'm happy to consider... Without that - fuck off.
5. 2021-01-04 10:38 Robert F. Garry open
   I think James is mainly commenting about the need for new PCRs based on some pairs missing some of the variants - yes that's obvious - at some point the PCRs need to be updated and obviously there is a need to keep monitoring. Does missing one primer out of three account for increased transmissibility? - likely not at all, but pretty simple to disprove. I don't think James is in the Lab Origins camp. He thinks he's found a "motif" that might signalpathogenicity. That is indeed a goofball notion [pathogenicity of a virus is something no one really understands], buthe does write in his missive that "None of the other coronaviruses analyzed had the pathogenic motif, making itpotentially useful as a forensic fingerprint. The pathogenic motif was not found in any constructed or modified coronavirus associated with Dr. Shi; she is, in my scientific view, exonerated as far as available and trustworthy data can inform us."

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