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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Fantastic review on chronic SARS-CoV-2 infections by virological superstars Richard Neher & Alex Sigal in Nature Microbiology. I’ll do a short overview, outline a couple minor quibbles, & defend the honor of ORF9b w/some stats & 3 striking sequences from the past week.
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First, let me say that this is well-written, extremely readable, and accessible to non-experts, so you should go read the full paper yourself, if you can find a way to access it. (Just realized it’s paywalled, ugh.) 2/64nature.com/articles/s4157…
Neher & Sigal focus on the 2 most important aspects of SARS-CoV-2 persistence: its relationship to Long Covid (including increased risk of adverse health events) & its vital importance to the evolution of SARS-CoV-2 variants. I’ll focus on the evolutionary aspects.
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In SARS-2 evolution, amino acid (AA) mutations get the lion’s share of attention—& rightfully so, as noncoding & synonymous nucleotide muts—which cause no AA change‚ are mostly inconsequential. But there are many exceptions, including a possible new one I find intriguing. 1/30
I’ll discuss four categories of such “silent” mutations, two of which might be involved in the recent growth of one synonymous mutation.
Maybe the single most remarkable example of convergent evolution in SARS-CoV-2 involves noncoding mutations: the multitude of muts in major variants that have pulverized the nucleocapsid (N) Kozak sequence.
I wrote about this below & a few other 🧵s 3/
@SolidEvidence There was yet another paper this week describing someone chronically infected, with serious symptoms, but who repeatedly tested negative for everything with nasopharyngeal swabs. On bronchoalveolar lavage (BAL), they were Covid-positive. 1/ ijidonline.com/article/S1201-…
@SolidEvidence BAL is very rarely performed, yet there must be dozens of documented cases now where NP-swab PRC-negative patients who were very ill tested positive by BAL. This has to be way more common than we realize.
If we had a similar GI test, I imagine we'd find something similar. 2/
@SolidEvidence Importantly, the patient was treated and improved, likely clearing the virus for good. Many, maybe most, chronic infections could be treated and cleared. But they have to know they're infected for that to happen. 3/
Read full 🧵for explanation, but the short story is that the best apparent escape mutations all interact w/something else—like a nearby spike protomer or other important AA—making mutations there prohibitively costly.
In short, the virus has mutated itself into a corner. 2/6
It's very hard to effectively mutate out such a local fitness peak via stepwise mutation in circulation since multiple simultaneous muts might be required to reach a higher fitness peak. 3/6
It's an interesting thought. I think the evidence is strong that all new, divergent variants have derived from chronic infections. The first wave of such variants—Alpha, Beta, Gamma—IMO involved chronic infections lasting probably ~5-7 months. It's controversial to say.... 1/15
…that Delta originated in a chronic infection, but I think the evidence that it did is strong. One characteristic of chronic-infection branches is a high rate of non-synonymous nucleotide (nuc) substitutions (subs)—i.e. ones that result in an amino acid (AA) change. 2/15
For example, if 80% of nuc subs in coding regions cause an AA change, that’s a very high nonsynonymous rate. The branch leading to Delta has 17 AA changes—from just *15* nuc subs! That’s over 100%. How is this possible? 3/15