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More from @ydeigin

Yuri Deigin

@ydeigin

Jul 13

🚀 More amazing partial reprogramming news! This time from @davidasinclair — he mentioned some unpublished animal results for:

- *reversing* Alzheimer’s symptoms
- hearing loss
- ALS
- glaucoma (anticipating clinical trials in 2025!)
- rejuvenating skin, kidneys and liver

Great to hear that the FDA is ok with Tet-inducible (via rtTA3) partial reprogramming gene therapies, and that Life Bio is so close to the clinic. They presented encouraging results in monkeys in an eye stroke model (NIAON); I didn’t know they also tried a glaucoma monkey model.

PS: while Life Bio seems closest to human clinical trials among partial reprogramming companies, others aren’t far behind:

- Turn Bio with their skin therapy
- we at YouthBio with our Alzheimer’s therapy

Read 6 tweets

Yuri Deigin

@ydeigin

May 8

🧵 I wrote a new Medium article about how Ralph Baric's January 2024 testimony provides new insights into the origins of COVID-19. Check out the article here:

yurideigin.medium.com/why-ralph-bari…

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Highlights:

- Ralph Baric confirmed that DEFUSE proposed inserting novel furin cleavage sites into live viruses, inspired by feline coronaviruses
- SARS-CoV-2’s furin cleavage sites is identical to the one found in several lethal feline coronavirus strains
- Ralph Baric strongly believes WIV had unpublished viruses and viral reverse genetics systems
- Most plausible Covid origin is the result of research on identifying new SARS-like viruses and developing broad vaccines against them

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Quick Summary:

Ralph Baric’s January 2024 testimony provided crucial insights into the DEFUSE grant proposal, a collaborative project involving EcoHealth and the Wuhan Institute of Virology (WIV), and the research interests of WIV prior to the Covid outbreak. The pre-Covid landscape of coronavirology research saw intense US-China collaboration aimed at creating broad-spectrum vaccines for SARS- and MERS-like viruses. Key players like Baric, along with researchers Lanying Du, Yusen Zhou, Fang Li, and Shibo Jiang, focused on overcoming challenges such as antibody-dependent enhancement (ADE). By 2018–2019, as collaboration between Baric and his counterparts shifted, WIV became central in SARS-like virus research.

Drawing on Baric’s testimony, I argue that the emergence of SARS-CoV-2 in Wuhan wasn’t coincidental but a likely result of research at WIV. In particular, I outline how WIV researchers, after a post-2018 shift in focus, concentrated on identifying SARS-like viruses with spike proteins 10–25% different from SARS1, capable of evading SARS1-based antibodies, and potentially causing ADE. They were plausibly inspired by Baric’s ideas on furin cleavage sites and his work with Fang Li on SARS and MERS spike cleavage, leading them to engineer furin cleavage sites into novel SARS-like strains. Baric’s testimony suggests that feline coronaviruses inspired this suggestion, and the identical furin cleavage sites in lethal feline coronavirus strains and SARS-CoV-2 strongly indicate that the WIV could have inserted such a site into a SARS-CoV-2 precursor to extend their research from MERS to novel SARS-like coronaviruses. This suggests the emergence of SARS-CoV-2 was not a coincidence but a potential result of this focused research.

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Yuri Deigin

@ydeigin

May 2

I was curious to hear Peter Dazsak mention at the @COVIDSelect hearing that prior to the Covid outbreak, he actually met with Dr. (Yi-Gang) Tong who was working on a SARS-like CoV found in pangolin samples. In his Feb 2020 paper, Dr. Tong mentions that they isolated this virus long before the outbreak and routinely cultured it at BSL2. More info in the thread below.

PS: Daszak erroneously claiming in 2020
that WIV didn’t have live bats goes to show that he could well be unaware of what other research relevant to Covid origins WIV was engaged in.

While Dr. Tong's lab is in Beijing, he did collaborate with WIV and EcoHealth previously, e.g. in 2018 on a SADS-CoV paper titled "Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin":

pubmed.ncbi.nlm.nih.gov/29618817/

But I am more intrigued about the collaboration between Yi-Gang Tong and Yusen Zhou, the author of the Feb 2020 Covid vaccine patent who died a few months later under mysterious circumstances. They both hail from the same "State Key Laboratory of Pathogen and Biosecurity" at the Beijing Institute of Microbiology and Epidemiology. Here is their joint 2016 paper:

ijbs.com/v12p1104.htm

Read 10 tweets

Yuri Deigin

@ydeigin

Apr 22

4 years after my first Medium article on Covid origins, I wrote another one. In it, I make the case that SARS-CoV-2 is precisely the virus WIV was hunting for in 2019.

Below is a thread on the key points:yurideigin.medium.com/sars-cov-2-is-…

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In 2018, WIV started looking for SARS-like viruses that were 10–25% different from SARS1 in their spike but could still enter human cells, and escape SARS1-based antibodies. SARS2 fits those criteria like a glove.

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Moreover, as I will show below, precisely because SARS2 or its BANAL-like progenitor could evade SARS1-based vaccines and antibodies, such strains would have been prioritized and likely turned into full-genome synthetic backbones.

Read 97 tweets

Yuri Deigin

@ydeigin

Apr 11

In our debate on Covid origins, Peter @tgof137 kept insisting that the DEFUSE proposal was only interested in viruses that are only within a 95% similarity to (i.e. at most 5% different from) SARS1. I thought I fully explained that Peter was mistaken and the judges have agreed with me (see the clip below) but Peter keeps repeating that claim (e.g. in the Astral Codex writeup).

Now, with the FOIA of the DEFUSE drafts we now have clear evidence that even strains with up to a 25% difference from SARS1 were of interest.

🚨 Moreover, the 2019 EcoHealth grant renewal letter for their joint grant with WIV actually said that they would PRIORITIZE strains that had between 10% and 25% difference from SARS1 in their spike gene.

Details in the thread below.

This is the relevant excerpt from the DEFUSE FOIA:

🚨 But this is an even more important piece of evidence as this is the 2019 EcoHealth NIH grant renewal application for their joint grant with WIV that has been ongoing since 2014. In it we see that by 2019 their interest has shifted to focusing on novel SARS-like strains that are 10-25% different from SARS1 in their spike.

It is also noteworthy that they are talking of anticipating finding another 100-200 novel CoVs by sampling 5000 bats.

ecohealthalliance.org/wp-content/upl…

Read 4 tweets

Yuri Deigin

@ydeigin

Dec 13, 2023

Skeptics of epigenetic rejuvenation via partial reprogramming often point to low efficiency of full reprogramming in support of their skepticism.

Indeed, under standard conditions in vitro, only a small proportion of cells forced to express Yamanaka factors end up finishing the journey to pluripotency. This has led skeptics to further suggest that the rejuvenation we observe in reprogrammed cells is a manifestation of selection of apriori healthier cells by the reprogramming process rather than bona fide rejuvenation.

However, several observations mentioned in the attached video argue against this. First observation is that essentially 100% of starting cells can be reprogrammed to iPSC by Yamanaka factors if their H3K36 repression is transiently ablated in the early stages of reprogramming. And secondly, the earliest stages of reprogramming actually open up chromatin in all cells, even in the ones that don’t end up transitioning to pluripotency.

I think this has implications for both safety and efficacy of epigenetic rejuvenation by partial reprogramming, as its goal is actually to avoid a change in cell identity while at the same time giving cells a quick epigenetic jolt in the hopes of resuscitating them back to a healthier state. If we now observe that essentially all cells expressing Yamanaka factors get that jolt in the first days of partial reprogramming, that’s quite encouraging.

So the video below has excerpts from interviews with Konrad Hochedlinger and Ken Zaret from this year’s Cold Spring Harbor’s Cell State Conversions Meeting, as well as from Ken Zaret’s excellent CSHL keynote there. I’ll post links to the original videos in tweets below.

Bonus: Juan Carlos Izpisua Belmonte asks two very insightful questions:

(Dr. Belmonte is one of the pioneers of partial reprogramming as he led the group at Salk that published the seminal Ocampo et al. 2016 paper. He is now at Altos Labs)