1/10 This shouldn't even be a debate. Who could argue against this? Knowledge is the ultimate public good, & to restrict access to scientific papers to those at academic institutions w/subscriptions to journals is a crime.
2/10 Out-of-control, continually strengthening copyright & patent laws are an economic weapon wielded by the rich against the poor and by enormous, monopolistic firms against small firms. This is a major driver of inequality that receives scant attention. cepr.net/technology-pat…
3/10 The alleged justification for strong IP laws is that they incentivize & facilitate innovation. But as @DeanBaker13 points out in his indispensable (& free) book Rigged, in their current form, IP protections greatly impede innovation. See Ch. 5 deanbaker.net/books/rigged.h…
4/10 How much has medical progress been stifled by the patent-driven secrecy under which private research is cloaked? And by the gross distortions that drive companies to pursue expensive, patentable treatments & ignore cheap, often greatly superior treatments? (Rigged, Ch. 5)
5/10 Apart from the baleful economic & scientific effects of our IP laws, it's worth considering some more indirect effects these laws have on public health. Patent monopolies unquestionable cause corruption in the pharmaceutical industry. @DeanBaker13 on the opioid crisis:
6/10 Understandably, the rampant corruptions & recurrent scandals in the pharma industry have led to public distrust. Skepticism about Big Pharma claims is of course justified, but it has led some to reject anything connected to pharma, including vaccines. statnews.com/2019/02/26/ant…
7/10 The anti-vaccine movement's claims are of course absurd & tremendously harmful to public health, but their outright rejection of all scientific evidence largely stems from the never-ending flow of pharma-industry scandals, which are a predictable result of patent monopolies.
8/10 There's been much discussion of how to combat misinformation during the pandemic, but little talk of one of the root causes: patent-monopolies. Public financing of drug research could eliminate patent monopolies & allow drugs to be sold at generic, free-market prices.
9/10 Until we reform our rotten, corrupt, patent-monopoly-driven pharma industry, public skepticism of even impeccable medical research will remain, and such distrust will continue to be exploited by charlatans & mountebanks peddling noxious nonsense, w/grave public consequences.
10/10 Chart in tweet #8 is from chapter 5 of @DeanBaker13's book 'Rigged.' The book is freely available in digital form, & an awesome intro into some of the most pressing economic issues of our time. Definitely give Ch. 5 a read if nothing else. deanbaker.net/books/rigged.h…
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I beg to differ! If it is not a sequencing mistake—and it looks clean—one of these BA.3.2 has something completely novel in SARS-CoV-2 evolution: an FCS-adjacent deletion!
One of the two QT repeats appears to have been deleted. I've never seen anything like this before.
Work by @TheMenacheryLab looked at a similar, more extensive, deletion. They deleted both QT repeats plus the next AA (∆QTQTN). In Vero cells (monkey kidney cells), it produced extra-large plaques & outcompeted WT virus—similar to furin cleavage site (FCS)-deletion mutants. 2/12
But in human lung cancer (Calu3) cells, the ∆QTQTN-mutant replication was dramatically reduced (2.5 orders of magnitude), and in infected hamsters disease was much milder. 3/12
There's a new BA.3.2.2 from South Africa today. For the most part, there's been little substantial change in BA.3.2 over the past few months—mostly synonymous mutations & very little happening in spike.
But this new one has 3 spike mutations & looks quite interesting. 1/7
For those not following closely, here's a 🧵 I made about BA.3.2 (not yet designated at the time) that I made some months ago, when it first burst upon the scene. 2/7
Attenuation of the SARS-2 furin-cleavage site (FCS) continues apace. It's beginning to look as if some form of FCS-weakening mutation might well become fixed in the near future. Collectively, they are at ~12% globally—a totally unprecedented level—& rising quickly. 1/4
In South America, this may have already happened. Recent sequences are scarce, but they nearly all have some sort of FCS-weakening mutation, mostly S:S680P in XFG.3.4.1, but with several others (S680F, S680Y, R683Q, R683W) contributing as well. 2/4
The enigmatic anti-correlation between S:∆S31 & FCS ablaters—clear since summer 2024—is strong as ever. Here are the recent CovSpectrum stats for T22N & ∆S31 among all seqs & seqs w/FCS weakeners.
How exactly a 1-AA deletion in a distant region affects the FCS is unknown. 3/4
There's been some speculation about why, despite persistent immune activation, germinal center activity, & overall elevated Ab levels, LC patients here had very low anti-spike Ab titers. I want to highlight one interesting speculative hypothesis & offer another possibility. 1/10
The ever-fertile mind of @Nucleocapsoid proffers the possibility that exosomes could be responsible for viral spread in some tissue reservoirs. I don't know much about this topic and so don't have much to say at the moment, but I'm trying to l learn. 2/
I'll offer one other possibility: the deep lung environment (or some other tissue reservoir) favors either an extreme RBD-up or extreme RBD-down conformation.
Background: The receptor-binding domain (RBD) of the spike trimer can be up or down. It has to be up to bind ACE2... 3/
A fascinating new preprint w/one very unexpected finding suggests, I believe, that a large proportion of Long Covid may be due to chronic infection in a particular bodily niche, which could be crucial for finding effective LC treatments. It requires some explaining. 🧵 1/33
First, a brief summary of the relevant parts of the preprint. They examined 30 people (from NIH RECOVER cohort) for 6 months after they had Covid, taking detailed blood immunological markers at 3 time points. 20 had Long Covid (PASC), 10 did not (CONV). 2/ biorxiv.org/content/10.110…
The PASC group showed signs of persistent, pro-inflammatory immune activation over the 6-month time period that suggested ongoing mucosal immune responses, including elevated levels of mucosa-associated invariant T cells (MAIT). 3/
Wow, BA.3.2 hits its 4th continent with a new sequence from Western Australia.
Reminder: BA.3.2 is a saltation variant resulting from a ~3-year chronic infection. It is very different from and more immune-evasive than all other current variants. 1/4
It was collected July 15, & is most closely related to the recent S African seqs from May & June.
It has an NSP5 mutation known to be beneficial (ORF1a:K3353R) & 2 new NSP12 mutations, which is unusual. Its 9 synonymous mutations indicate it has been circulating somewhere. 2/4
Seems clear now that BA.3.2 is not going away anytime soon. Its overall impact so far has been negligible, but at first BA.2.86's was as well. Once it got S:L455S (becoming JN.1) the dam burst & it set off a new wave in the global North. The question now is.... 3/4