November 12, 2025

📺 The Great British Baking Show Series 16 had fewer anxiety attacks and temper tantrums, and was more enjoyable to watch than last year’s. Still, the sheen is beginning to wear off, the artifice of it is becoming more and more apparent, and am I being a horrible person just for liking that a contestant doesn’t get all teary-eyed when kicked out?

Want to introduce some drama? Have people make madelains — a desert that needs at least four hours for the batter to chill to achieve its characteristic “hump” — in 2 hours 15 minutes total and then stress about not doing it correctly. Or, come judging time, be a bit more circumspect about the clear favorite and heap praise on the also-rans so that you can hem and haw about your very difficult choice. Also, is it just my middle age performing mind tricks or are the contestants getting ever-younger? Will there be a point in a decade’s time when Junior Bakeoff and the main attraction meld?

It is still by far the best “reality TV” one would come across, and following it from beginning does make one more interested in baking. As its cultural relevance grows, however, so does the amount of pressure it puts on the bakers, to the point of unpleasantness. Luckily, the finalists this year were wise beyond their years, but how many more people are left in Britain with that kind of mental fortitude?

November 11, 2025

🏀 Cursed, yet again (and again).

The only team who managed to lose to the Wizards so far this season just booted their GM.

Tuesday Twitter hits, biotech yet again (maybe I should expand my follow list)

November 10, 2025

Three links for Monday, and I am in a disagreeable mood

November 9, 2025

Sunday aftenoon links, mostly biomedical

November 8, 2025

🍿 Watched: The Twits (2025), an attempt to draw out Roald Dahl’s slender book about an insufferable couple into a 100-minute feature film. In the process, they made a truly classical piece of Netflix polished excrement.

What they should have done was a series of short vignettes, Tom & Jerry style, that could have all been physical comedy with hardly a spoken word. Booba and Gudetama — both streaming on the same service — are good examples. But no, the movie that is nominally about the Twits instead revolves around 10-year-old orphans who behave like adults and magical creatures that belong to Dr Seuss more than to anything Dahl wrote. Even the eponymous couple behaves altogether differently than in the books: the Twits I know would never have cooperated long enough to build a fully (if barely) functioning theme park.

My own children — two of whom have read the book — quickly saw past the gimmick and lost interest despite the beautiful animation and a million things happing all at once for the sake of keeping their attention. In contrast, they have seen — of their own volition — The Mitchels versus the Machines, Spider-Man: Into the Spider-Verse and more or less the entire Studio Ghibli repertoire countless times. With all of those still available, what exactly was the point of The Twits?

November 7, 2025

And then there were six (parents inclusive). Pardon any potential interruptions to our scheduled programing.

November 6, 2025

🎮 Our 6-year-old has completed both Astro Bot and Astro’s Playroom, mostly by himself, with minimal help from older sisters, and when I say “complete” I mean digging into every nook and cranny and getting all of the trophies. Quite the soundtrack, too (Crash Site is the favorite).

November 5, 2025

Long-ish read of the day, on biotech

Where are all the trillion dollar biotechs? asked Lada Nuzhna in her rarely updated blog. I will paste only the conclusion but the entire post is thoughtful and well-documented:

Drug development, like any other industry, is greedy - it addresses the most tractable diseases with the biggest outcomes first. Genetic targets, clear biomarkers, and one-pathway wins gave rise to the biotech boom of the 70 and 90s, when recombinant insulin, monoclonal antibodies, and early gene therapies created a sense of an endless frontier. Unlike with other industries, reinvesting capital from those early wins back into the ecosystem didn’t accelerate industry’s progress – we’ve been on a reverse trend for a while now. Today, remaining problems resist the very playbook this industry was built on.

Most industries have eras when progress stalls before a new paradigm unlocks scale again. Electricity needed transmission grids, computers needed operating systems, and aviation needed jet engines. For biotech, whether the shift will come from new modalities, new regulatory frameworks, or entirely new ways to validate efficacy in humans is not yet clear, but we can, perhaps, outline the boundaries within that future will exist: manufacturing and trials should get cheaper with each run, regulations should become more adaptive, approval frameworks should increase and not decrease in variance, and new therapeutic modalities should focus on unlocking new biology, not just producing slightly better iterations on problems we already know how to solve. Until those new paradigms take hold, building a trillion-dollar biotech will remain caught in Lewis Carroll’s logic: running as fast as we can just to stay in place, and twice as fast to make any real progress.

Note that “trillion-dollar biotech” is (hopefully) just shorthand for a company that produces truly world-changing drugs, and is rewarded accordingly by the all-knowing all-seeing Mr Market to reach a trillion-plus valuation. But if you put dollars first and benefit to humanity second, would that not perhaps contribute to these Alice in Wonderland dynamics? Maybe it’s the gold-digging approach to this decades-long gold rush that caused the shovels to become so expensive, maybe even more valuable than hitting gold. More than that: hitting gold — i.e., developing an effective drug — in this topsy-turvy world can even get you punished.

As Kyla Scanlon stated so succinctly, it is a casino economy now. In biotech it isn’t just now but from its very inception, as I have recently learned, and surely there are downstream effects in this approach to drug development. Again, Nuzhna’s blog post is exceptionally well-written and researched but maybe just maybe the problem deserves to be reframed?

November 4, 2025

An interesting series of biotech headlines

All this for drugs that cost millions of dollars per dose from a company with $2B in revenue. Neutral people in the know have their opinions too. Know me by my enemies indeed.