Ok, we need to set the record straight about how the DRASTIC schism happened. And no, it’s not because of the Radical R, although many of us did want to change it once we realized Billy originally used it for his RAGE University years ago:
Needless to say, most DRASTIC members want nothing to do with such radical anarchist messaging which we never signed up to endorse:
But what precipitated our decision to separate from Billy was the revelation that he appropriated the group email access and his subsequent refusal to comply with group’s majority vote to share it with the group’s appointee.
The original group email was created by @RdeMaistre, and he then shared its password with EdgeOfTheLeaf who was the website admin at the time. Later Rodolphe found himself locked out, and then learned it was Billy who changed not only the password but also the recovery email.
Billy then told Rodolphe a ridiculous story how EdgeOfTheLeaf deleted his Twitter account because of either getting cancer or fearing that he has compromised his anonymity. Surprisingly, Edge didn’t bother telling anyone else this or any other story before disappearing.
We found out about all this when @Rossana38510044 challenged Billy for his dictatorial behavior over access to journalists & filmmakers, but instead of agreeing to restore group access to email Billy insulted Rossana and then locked her and 3 more members out of the group.
That was on October 2, and a multi-day crisis ensued where several members tried to convince Billy to share group email access but to no avail. The group then held a formal vote to compel Billy to share email access with at least me but he still refused.
At that point we had no other choice but to create a new email and website, as Billy controlled both at the time. However, revealing his true terrorist nature, he threatened to engage in a slanderous smear campaign against me if we chose to make the new website and email public:
The group agreed that we do not negotiate with terrorists, and after we set up the new email and constructed the website, we made the announcement of distancing from Billy and his website.
Changing what DRASTIC stands for was proposed *after* the decision to split off from Billy, and was put to a vote in the original DRASTIC group, to which we were added back once Billy was removed.
As Andre and WhereIsHuangYanling left the group before that vote, 21 members remained, so 13 votes for and 1 abstention were enough to pass the proposal.
In closing, we never wanted to make this dirty laundry public, but with Billy’s misinformation campaign trying to portray the split as a result of disagreement on the name change we had to set the record straight. And no, rebranding was not my idea, although I fully support it.
Also, I am not trying to become “the leader of DRASTIC” or portray myself as some sort of “coordinator” — DRASTIC is and will remain decentralized and fully democratic. But I *will* always stand up to bullying, as that is something I simply cannot tolerate.
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Latest SARS2 preprint provides additional evidence that not only was the novel FCS a key factor in its pandemic potential, but the way the FCS was acquired — via a 4 aa insertion — was also important. Re: "why would a genetic engineer use an insertion to create an FCS?"
I've hypothesized previously that the answers to "why use an insertion" and "why use a leading proline" lie in MERS, whose S1/S2 loop is 4 AAs longer than that of SARS-like CoVs, and also has the leading proline, making it more exposed to proteases:
So the desire to try a MERS-like FCS can explain both. Moreover, in the 3D structure of the spike protein, the S1/S2 loop in SARS2 with the insertion has its cleavage point ~3x closer to the MERS one than if the FCS in SARS2 arose w/o insertion:
Increasing neuroinvasiveness could indeed have been the research goal of a genetic engineer opting to use a “suboptimal” or “non-canonical” furin cleavage site like the one found in SARS2. And Baric did say that MHV and FIPV inspired the FCS interest of DEFUSE. Thread below:
Somewhat counterintuitively, in a human coronavirus, OC43, when it has the less efficient (“suboptimal”) RRSR furin cleavage site instead of the canonical RRSRR one, it is more lethal and more *neurovirulent* when tested in a mouse model:
But in a mouse hepatitis virus (MHV, one inspiration in DEFUSE) it is actually the JHM strain with the more efficient FCS, RRARR (reminiscent of RRAR in SARS2), that is *more* neuroinvasive and more lethal than the A59 strain with a suboptimal RRAHR FCS:
Excellent analysis of SARS2 cryptic lineages from persistent human infections (those nightmare scenarios happen when the virus colonizes your gut and remains there for months or years). Some implications for Covid origins there that I’d like to address in the thread below.
First an aside on extrapolating insertions found in SARS2 circulating in humans to the likelihood of insertions occurring (and getting fixed) in a SARS2 progenitor circulating in an intermediate host — SARS2 has now been circulating for years in hundreds of millions of humans, while in the wild it could not have had even a sliver of such a reservoir of non-bat hosts (and we all agree the FCS insertion could not have arisen in bats because it is detrimental to their preferred enteric tropism).
Of course, “a long time” for passaging in a lab could be just a few months, especially if we’re talking about in vitro passaging. Moreover, many novel mutations would arise quickly when the virus is put into cells from a novel host and organ system (respiratory vs. enteric).
🧵 Covid Origins: Lab leak critics claim the coincidence of a novel coronavirus emerging near the Wuhan Institute of Virology is dwarfed by the “counter-coincidence” of it first being noticed at a wildlife market. But the market was actually one of the most likely places for a lab-leaked virus to get noticed.
Here’s a clip from my podcast with @robertwrighter and a deep dive in the thread below:
Basically, if we imagine the map of Wuhan as a “probability landscape”, where each location has an inherent probability that a roaming lab-leaked virus would get noticed if it got there, the Huanan seafood market would dominate that landscape like Mount Everest.
Now, let’s walk through the thought experiment: How would a lab-leaked virus get noticed in Wuhan in late 2019?
Some critics of the Covid lab leak hypothesis say the SARS2 furin cleavage site is unlikely to have been engineered because in previous cases of creating novel FCSes in coronaviruses virologists have never inserted an FCS but rather created them in place via point mutations. But!
A close collaborator of Zhengli Shi and the Wuhan Institute of Virology, Shibo Jiang, in 2013 published a paper creating a furin cleavage site in a non-CoV synthetic vector via a 12-nt insertion (note the CGG codon for the leading arginine):
In 2016-17, WIV has created a novel reverse genetics system ("backbone") for the WIV1 virus, and Shibo Jiang subsequently coauthored a paper with Lei-Ping Zeng, the author of that backbone. (Lanying Du, another key collaborator of both WIV and Shibo Jiang, was also on the paper. She was also the editor for the 2013 paper inserting the RIRR FCS):
🚀 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