August 20, 2025

Mid-week links, moderation edition

Robert Caro’s books are about formidable, single-mindedly devoted characters with storybook life arcs. It may be the case, then, that the only person who could write the biography of Robert Caro is the man himself.

  • John Gruber: Gold, Frankincense, and Silicon. The amount of money and power one obtains in life are proportional to the size of frogs — or, if you are feeling less charitable, turds — one swallows throughout life, and at some point you either acquire a taste for frogs (maybe you’ve always liked them!), spend a lot of money on therapy and/or drugs, or drop out. And Tim Apple hasn’t dropped out just yet.
  • John Gruber again: OpenAI Brings Back Legacy ChatGPT 4o Model in Response to Outcry From Users Who Find GPT-5 Emotionally Unsatisfying. To quote Gruber, “These people need help, and that help isn’t going to come from a chatbot.”
  • Duncan McClements: The Sun Never Leaves. The subtitle is “How emigration ended the British Empire”, and it could not have happened to a nicer bunch of overindulgent cut-throats.

Happy reading.

August 19, 2025

The FT Editorial board says it’s time to stop indulging Serbia’s authoritarian president:

America seems to have left the Balkan pitch for now. But the UK and the EU have not. They should act and use their economic leverage. If they do not and Serbia heads further down the authoritarian path, it will be not just Vučić but also his gaze-averting western backers who are to blame.

“Economic leverage” sounds suspiciously like sanctions, which would be the exact wrong move to take and would only strengthen the president’s hand. Just ghost him — it would infuriate his small narcissistic mind.

August 18, 2025

Alex Tabarrok wrote a brief comment on why America always wins in the global superpower game:

Double down on immigration, entrepreneurship, innovation, building for tomorrow, free markets, free speech and individualism and America will take all new competitors as it has taken all comers in the past.

Funny how each and every of these reasons of America’s dominance is not only under threat — they always have been — but is being actively dismantled by the state itself. This time may truly be different.

August 16, 2025

With successes like these, what happens to the failures?

Whatever you think of medicalization of moderate obesity, the GLP-1 inhibitors semaglutide and tirzeparide (aka Ozempic, Wegowy and Zepbound) are truly groundbreaking. It takes a lot for me to admit something approaches imatinib in innovation and importance, and they are there! Incredibly, the drug companies that developed them are considered losers in the upside-down world of American finance:

Since their peak last year, the decline is more pronounced. Novo Nordisk has lost $367bn in value since its peak in June 2024, a fall of more than two-thirds, while Lilly has fallen 29 per cent from a record valuation last year, wiping $250bn off its market capitalisation.

In a decision that was short-termist and reactionary to the extreme, Novo Nordisk even fired their longstanding CEO over it.

The kicker comes from a healthcare fund manager quoted near the end of the article:

“If you’re a generalist investor, why are you putting money here, versus buying an AI stock, [given] the headwinds of both tariffs and the most favoured nation policy?” he added.

What are we even doing here?

August 15, 2025

A wonderful example of why you should always check the primary sources from Andrew Gelman: When fiction is presented as real: The case of the burly boatmen. Caveat lector. Yes this applies to peer-reviewed literature as well. (ᔥAndrew Gelman, who self-cited)

August 14, 2025

A few good links for the not-quite-yet weekend mood

Enjoy.

August 13, 2025

📚 Finished reading: The Occasional Human Sacrifice by Carl Elliott

The Occasional Human Sacrifice puts faces, personalities, anxieties and neuroses to the names of people who acted as whistleblowers to some of the biggest ethical failures in clinical trials. Some are textbook, like Tuskegee or the Willowbrook hepatitis studies, but many were either new to me, or just barely registered when they were briefly covered.

Elliott was himself a whistleblower in the case of Dan Markingson so he is hardly impartial to their cause — caveat lector — but the cases presented seem truly egregious. And not all of them are ancient history: Paolo Machiarrini experimented on humans without oversight as recently as 2014.

The picture you get is bleak and does not fill one with confidence about clinical research anywhere in the world. Physician-scientists are careless at best, selfish profiteers at worst, people who sit on ethics committees are a bunch of box-checkers, institutions are insular and protective of their own. Of course, there is major selection bias going on: yes, institutions protect their own but then there are many of their members who are accused daily of misconduct by conspiracy theorists, biopharma lobbyists, and the occasional psychopath. Some IRBs are indeed approval mills, but then there are those which truly protect research subjects, though alas what they do doesn’t make it into a book. How to tell where the equilibrium should lie?

In fairness to the book, it does not pretend to be a grand unifying theory of what is wrong with medical research. It is a collection of vignettes, no more and no less, and as such is an important source of “real-world” information to the research community. It is also a big honking red flag to any person thinking to blow the whistle on wrongdoings medical or not: it is a difficult path to take, with no vindication at the end.

August 12, 2025

Is lithium deficiency an important factor in developing Alzheimer’s disease? A recent paper in Nature provides some convincing evidence, mostly from mice. For example:

Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice.

I know quite a few doctors who would say lithium (carbonate) deficiency is responsible for many behavioral issues in adults, but this is not what they had in mind! (↬Derek Lowe)

August 11, 2025

In the story of Spanish solar power, the FT finds a country with energy abundance and doesn’t like what it sees. A few choice quotes:

Pedro Sánchez calls his country a ‘global benchmark’ in the transition to greener energy, but prices — and profits — have plunged.

Spain has built so much solar capacity that at certain times of day it produces far more electricity than it needs. Prices have plunged as a result, dragging down owners’ profits with them.

Free power is gratifying for customers, but bad for generators.

Etc, etc. Good for Spain! The monetary matters will settle themselves out.

August 10, 2025

For your Sunday reading pleasure

There is banger after banger in the most recent weekend edition of the FT, which is apparently Steve Bannon’s favorite newspaper:

Cave turns to me. “So what’s your skill then, spinning stuff into a story?”

“No,” I reply. “My skill is keeping a straight face when someone tells me something, and inside I’m thinking: fucking hell.”

All gift links with limited activations, so enjoy while you can!