• Science: A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging. Or: why are naked mole-rats the longest living rodents, and not by a small margin? Seems important.
• FT: The quest to make young blood into a drug. Vampiric.
• NIH director embarasses himself on X. I am all for promoting healthy lifestyles, but one can do so without posting dubious charts from suspicious sources.
• All Derek Sivers’s e-books are free until October 18, prints are $4 each. All are highly recommended, particularly Useful Not True.
• The Drifter looks like a cool game for those who liked old-school point & click adventures. It’s in my Steam pile (yes, that’s how I’ll call it… ᔥRobin Rendle).

• Aidan Walker: now is not the time to ban phones. The Gen Z case against Jonathan Haidt, with whom I generally agree. Walker makes some good, if muddled points. In any debate about children, school and phones it is important to distinguish the extent of a ban (during class — absolutely, at recess — we can discuss the pros and cons), which kind of phones are to be banned (smartphones versus others, and nowdays they all come on a spectrum), and maturity of a child (there are some 12-year-olds who are mature enough to babysit and some who cannot be left alone by themselves, and in the same family!) So it is an issue with some subtetly and since both social media and public policy ale places where subtetly goes to die I do not expect these questions to be answered any time soon.
• Ted Gioia introduces Jared Henderson: The Honest Broker Launches an Interview Series with Our First Guest Cory Doctorow. Henderson being the host of the interview, posted on Gioia’s Substack page. Doctorow’s book Enshittification has just been published and even though I suspect it is one of those that could have been a blog post it is indeed on the pile. Doctorow’s closing recommendation, Letters from an Imaginary Country, will also end up there when it comes out.
• Casey Handmer: Career Development Guide for Job Seekers. Advice for academics and government employees who want to switch to industry, from the perspective of an engineer. Fortunately biotech is more forgiving or else I would never have made the transition but I imagine things are even more competitive now than four years ago so all this is helpful. More boradly, academia and industry have so many “false friends” — conventions and processes that have the same name but are different and in some cases diametrically opposed — and the interview stage is just the tip of the iceberg.
• Scott Sumner: Fat tails. It is more about slippery slopes than fat tails, but Sumner has never been one to write a good headline.

Don’t go to Maine, it sucks.

📺 The Night Of (2016) we somehow missed when it first came out nine years ago (!?) but it was well worth revisiting. These kind of competent dramas with a deeper message than just whodunnit have become rare — was Mare of Easttown the last one? — particularly ones that feel like they were set in an actual place and not a softly-focused, sterilized backdrop of Netflixland.

The complete package is high enough quality to compensate for a few annoying stereotypes. Cutting to a street scene full of Southeast Asian pedestrians milling about? Queue vaguely ethnic music with a techno beat. Our innocent protagonist is sent to a penitentiary like a lamb for slaughter? Queue the wise black inmate to provide advice and protection… but is he himself in fact a wolf?

That whole prison story was a needless diversion, a sped-up Walter White to Heisenberg transformation which detracted from (to me) the more important message about the criminal justice system and all human systems in general. It says that competence in a profession is indistinguishable from obsession, is driven by annoyance not love, and is powerless against the greatest force of human civilization — institutional inertia. Application to medicine comes immediately to mind, a case of missed diagnosis standing in for wrongfully charging someone with murder. Now that would be a show to watch.

• José Luis Ricón: Systems Biology: understanding beyond genes. With an eye towards aging, but broadly applicable to much of medicine. As ever, there is a relevant xkcd comic on the topic (ᔥDerek Lowe).
• L. M. Sacasas: The One Best Way Is a Trap. “So, once again I invite us to ask a simple question: Is there, in fact, “one best way” in every realm of experience? And even if there were, at what cost would we discover it? And what would we gain? Might it be that in the course of pursuing the “one best way,” we would lose our way in a more profound sense?”
• Anthony DiGiorgio on X: Imagine we mandated everyone have car insurance that covers new tires, oil changes, and wiper fluid. I think you can guess where this is going, and he is not wrong. The cost of health care is skyrocketing because we are always finding new ways to spend money, and isn’t America a society of maximizers?
• Kyla Scanlon: Who’s Getting Rich Off Your Attention? Robert Reich responds, on Bluesky.
• Bonus: Tyler Cowen doubles down on min-maxing the society in his brief comment on Sora 2. “Still, from my distance it seems quite possible that the “slop” side of the equation is a simple way to fund AI “world-modeling” (and other) skills in a manner that is cross-subsidized by the consumers of the slop.” That way may be simple, but also quite diabolical.

🍿 One Battle After Another (2025) was, I imagine, the best movie I will have seen this year. I went into the theater not knowing anything about it except that it is a PTA movie starring DiCaprio, and for the first few minutes I had to orient myself on whether it was set in the present day or the 1970s — initially because of the subject matter, but mostly because of the (beautiful, unforgettable) cinematography that resulted in more than one iconic scene. Should I remind you that I see the late 1960s/early 70s as the pinnacle of American movie-making? This is as firm a recommendation as you will get from me to go see a movie.

🍿 Weapons (2025) brought me back hope that Americans still know how to make movies. It is a simple story well told, which trusts the audience to make the appropriate inferences — important for a competent horror — and has an overarching point to make on the bias towards normalcy. Will re-watch!

There isn’t one, because we still don’t know how acetaminophen works.

Aspirin has been in use for thousands of years and what it does to the body was a mystery for 90% of that time. But no more: ibuprofen, diclofenac and other NSAIDs all use the same mechanism, inhibition of two enzymes that promote inflammation, cause platelets to be sticky, but also destroy your stomach lining. We tried to get cute and selectively inhibit only one of those enzymes because the other caused gastritis, but that didn’t go well. That part of the aspirin family tree was cut short. There is, however, a whole separate branch that builds on aspirin’s effect on platelets. The more we know the more we don’t know, and at the edges of our knowledge lie new drugs.

The acetaminophen family tree is a stump. On one hand this isn’t a surprise: we have only known about it for 150 or so years. But then pure aspirin was synthesized around the same time — it was just willow bark extract ⊕ Acetaminophen was derived from coal tar so it is, in fact, coal tar extract. Somewhat off-putting for something to be taken by mouth, though coal tar can do wonders for dandruff. before the late 19th century — and look at how much we have learned since then. The best we have come up with is that acetaminophen works sort of the same way as aspirin, but only in “the central nervous system”. Vagueness covering for ignorance, like ⊕ The cure? Heavy cream and butter. generic life “stress” causing stomach ulcers.

Our knowledge gaps are so large that we still can’t agree on the name. Is it acetaminophen (APAP for tired interns who hand-wrote their notes) or paracetamol? Or just Tylenol? More vagueness.

Which is to say, there can be no mechanistic arguments for APAP risks and benefits as we know nothing about the mechanism: all inferences must be made empirically. And our 150 years' worth of popping coal tar pills have shown them to be safe for everything but the liver.

Still, it is worth acknowledging that APAP is a molecule extracted from coal tar whose mechanism of action is unknown but has something to do with the central nervous system. If someone described such a drug and then asked whether it could be behind some disorders of the brain, would you find the question completely whackadoodle? I would not. And would in any case practice myself and recommend to my patients via negativa, whenever possible and sensible.

The number of ways in which one can spend money for biomedical science is infinite. America has sunk trillions into genetics research, with a few important wins to show for it but not nearly as many as hoped for in the early 2000s. ⊕ For those too young to remember, this is the time when media were full of headlines about scientists finding the gene for x, where x was everything from hypertension to obesity to being gay. None of them panned out. Would a fraction of that being allocated to figuring out how one of the most widely-used drugs actually works be such a waste?