It wasn’t my imagination: the MacOS 26 Tahoe slowdown I noted immediately after upgrading was due to an Electron bug. Shamelectron (↬ATP) is a website that helpfully lists all Electron apps that are yet to fix it. The last holdout on my Mac has been Logitech’s Logi Options, which is now deleted and everything is — knock on wood — flying like before. Whew.

🎃 At a friend’s recommendation, our trio of children dressed up as Greg, Wirt and the frog from Over the Garden Wall, a family favorite for over a decade now. To our surprise and delight, they kept being recognized. A group of millennials handing out candy even broke out into song (To Adelaide, then Potatoes and Molasses). “Greg” had some candy in her pockets to throw out each time people guessed, but soon ran out and had to recycle the hard-earned treats from her bag. So, I’d call this Halloween a great success.

Rejoice: our national nightmare is over, at least until March.

The Billion-Dollar Molecule tells the story of the late 1980s and early ’90s world of biotech. The only change since then has been that ⊕ Well, there is one more difference. One billion United States dollars in September 1989 is 2.5 billion of 2025’s USD. one no longer faxes a manuscript and sends supplemental materials by snail mail when submitting to the journal; the personalities, incentives, tradeoffs and challenges are all the same.

Also typical of biotech, and sobering, is that 95% of industry-led research Werth described in the book did not matter: for all the lofty ideals of rational drug design espoused at road shows in investor slide decks, Vertex would chase one fad after another hoping for a hit. Once it got one, a truly life-changing set of drugs for cystic fibrosis, it had burned through so much money and became so profit-driven that it actively blocked low and medium-income countries from developing generic versions. Score for big pharma, which has no qualms about giving away drugs where they are needed.

The story was engrossing enough for me to tolerate Werth’s pulpy writing style, full of adjectives for tortured scientists and smoke-filled rooms. One could easily imagine it serialized on Netflix with distinct chapters, and it had indeed been shopped around, apparently without success. That last link ends with a side note that a movie about Theranos was also planned, and the juxtaposition is apt: more than once Werth notes the dramatic discrepancy between what Vertex management tells investors and the ground truth in the labs. There is certainly a difference between the sociopathy of Elizabeth Holmes and the goings on at your typical fly-by-the-seat-of-your-pants private startup, just not as large as you may think. This is, after all, why most of them go bust.

The story of the United States Food and Drug Administration is a story of mismatches.

Mismatch one: cramming both food and drugs regulation into a single agency. Humans have been making food since the beginning of time — it is in fact one of our defining characteristics — and while the methods have become more and more intricate and our definition of food wider and wider to now include some decidedly unfood-like substances it is not a field where people expect too much experimentation and adding risk to production yields absolutely no reward to the end user. Drugs as used now — aspirin aside — are a modern invention. We learned about DNA less than a century ago and cell & gene therapy weren’t even an idea until late into the 20th century. An eye-blink, compared to food. And when it comes to production, risk is very much encouraged for those who need the drugs, particularly for rare diseases without approved therapies.

That is the second mismatch, one within the Drug section of the FDA: generic drugs that have been used for decades are more like food, unapproved, experimental treatments are quite the opposite. This is a source of constant tension that leaves much room for improvement. To be clear: Europe is worse. EMA requires drugs tested at any stage to be manufactured in a fully audited manufacturing facility; FDA allows for “phase-appropriate GMP compliance”. This still requires major investment, lest you leave yourself exposed to the whims of a random audit.

The third mismatch, one written up in STAT this morning, is one of management. Regulation of food and established drugs requires a certain mindset and personality type; regulation of experimental drugs is something else entirely. There is a paradox here: while most of FDA’s work is focused on the first two — it is the baseline activity absolutely essential for proper functioning of society — the focus of the public is mostly on the third. Unless, of course, something goes wrong which it amazingly rarely does considering the amounts of food consumed in this country. But the culture has been determined by this baseline activity, and I imagine people going to work at the FDA self-selected for that kind of culture: steady, stable, contemplative, detail-oriented and intentionally boring.

Which is to say, I am not at all surprised about reactions like this, where I can absolutely see both sides of the story and in fact agree with both. But the tie-breaker is this: the steady-as-she-goes leadership of what should be the leading edge of innovation has led to the US getting further and further behind China all while its taxpayers are bankrolling said innovation. This state of affairs is untenable and all the policy memos in the world won’t help unless this root mismatch is resolved.

If you figure out a way to do it — and do it with urgency — that does not involve breaking up the FDA into at least two pieces, do let me know.

📺 Six episodes in, Season 5 of Only Murders In the Building — the only show we were excited about on Hulu — has been a thorough disappointment, and now Disney+ hits us with a whooping 100% increase in the annual subscription for its package deal. Granted, we were grandfathered into the $80/year plan and the new one is still better than the current price of standalone Disney+ Premium, but still — how much is it worth to pay for something you will never use?

By the way, the link above is to the Disney+ pricing website, and it is confusopoly on steroids, a roadmap to the world Philip K. Dick so brilliantly described in Ubik. I regret every bit of schadenfreude I had canceling cable.

📺 Slow Horses, Season 5: even better than the last. Less violence (season opener notwithstanding) and more laugh-out-loud moments in this one, which was fine with me!

• Nassim Taleb breaks with Russ Roberts. I learned about EconTalk from Taleb, after he wrote it was the only podcast worth participating in as a guest. The two haven’t had any public exchanges in two years so this was not much of a surprise. I continued listening to EconTalk, though with mixed feelings.
• A podcast on AI and medical progress. It is four hours long and I have no time to listen but I may run the transcript through an LLM to get a summary and a false sense of knowledge and understanding.
• Where are the Mozarts of our time? On one hand I agree that too much of the “top talent” is “wasted on writing algorithms to move trades a quarter of a thousandth of a millisecond faster.” On the other hand, isn’t Lin Manuel Miranda the Mozart of our time?
• Why are doctors less respected? Because “optimizing performance” and “curing disease” are two different things entirely, and you can’t do both while also acting as the nanny nagging about car seats, guns in the household and other matters which have much to do with well-being but nothing with disease.
• What happened to Harvard? This is so confirmatory of everyone’s worst fears about the Ivy League schools that I remain skeptical.