• Ruxandra Tesslo and Asimov Press: Clinic-in-the-Loop

The case for faster bench-to-bedside-and-back type of research, with which I agree. It is remarkable, however, how each generation interested in biomedical research reinvents the wheel without checking prior art. I would also argue strongly that the (correct) thesis of the essay is not a refutation of the biotech-as-casino hypothesis but rather its confirmation, unless you enlarge “biotech” to include academia and government research but then what are we even doing. Investors have no patience for nuance and view clinical trials as dichotomous regardless of how companies try to present them, and interpreting translational research results requires even more patience and tolerance of ambiguity.

• Elizabeth Ginexi: The Quiet Power of Program Officers

Ginexi has been a program at the NIH for more than two decades, so caveat lector, but many POs are indeed mini-Moseses in their scientific domains. On one hand they perform important and valuable work, on the other the importance of a single human being to the careers of investigators young and old tend to favor those with soft skills of communication more than those of scientific and intellectual rigor. No judgements on my end because I genuinely can’t tell if the alternative would be any better.

• James L. Olds: A Grant Reviewer’s New Year Advice to Proposers: What I’d Tell My Younger Self

Some genuinely good advice on how to write grants in a way to increase the odds of them being funded, with emphasis on accepting the reviewers’ comments and suggestions and approaching the grant resubmission as one would an offer to revise and resubmit a scientific manuscript, with much thanking and back-bending. Do keep that in mind when you read the next item.

• Laurel Raffington: Academia is just a job

This is true for most, as there are far too many academic right now for all of them to have soul in the game. However, academia continues to ask for more than it gives back out of too many people, while at the same time putting a negative selection pressure against people who are stubborn, single-minded and thus predisposed to a soul-in-the-game phenotype (see above). The only reason why the system survives at all is that the churn has been too low to fully reveal the tension, but it continues to creep towards the breaking point providing yet another case study of things that happen gradually and then suddenly.

• Guru Madhavan: Compulsive tracking doesn’t measure what really counts. And this is not even taking into account Goodhart’s Law
• Diana Mariska and A. Anantha Lakshmi: Move over, Tokyo — the world has a new biggest city. It is Jakarta, which its own citizens call — and I don’t know if they actually do or if it is an FT-ism but I find it delightful — the Big Durian.
• Stephen Bush: Creativity thrives with constraints. I nod my head in agreement even as the whole family is giddy in anticipation of what will inevitably be another polished turd to premiere on Netflix tonight at 8pm EST.
• Jonathan Vincent: How the AI ‘bubble’ compares to history. But why the scare quotes, oh FT?
• Janan Ganesh: The case for denial. It all makes sense until you find yourself missing the last train out of Berlin.
• Hannah Shuckburgh: Should you have a library in your loo?. Without getting too personal I would like to point out that my reading history would have been dramatically different — and poorer — had there been smart phones back in the day.
• Chloe Fox: **I opened a bookshop. It was the best, worst thing I’ve ever done **. A better way to keep books, though realistically the loo is more in my wheelhouse.
• Aimee Farrell: Green Knowe, the house that inspired a children’s classic. It is about the oldest inhabited house in Britain, which is all well and good with some great-looking photos but then I imagine walking in and hitting a wall of mustiness.
• Mark Ellwood: Instagram is coming for your house move. Good. Lord.
• Oliver Smith: I went in search of spiritual renewal in Japan — and ended up being dangled off a cliff. Good. Lord. Though in a different way.

Enjoy!

• Ben Sasse (@BenSasse): Last week I was diagnosed with metastasized, stage-four pancreatic cancer, and am gonna die.. I first learned about Sasse from his conversation with Tyler where he presented himself as a down-to-earth, sensible nerd. In that light, his short and turbulent tenure as University of Florida’s President was not a surprise: “Dr. Sasse didn’t have much respect for the U.S. News & World Report rankings, but the university’s politically connected board of trustees very much did.” And now this. So it goes…
• Caleb Watney (@calebwatney): OSTP asked for concrete suggestions to accelerate American science. Here are our thoughts. In a world where people like Ben Sasse were still in politics these kinds of sensible solutions might have had a chance of being implemented. But the recommendation that “the administration should prioritize visa applications for researchers and entrepreneurs…” would have to wait for the likes of Stephen Miller and his nativist friends to leave the premises.
• NonsparseOncologist (@5_utr): Is “Precision Oncology” just marketing? The thread suggests that it is, and I can confirm. The word scores quite well with both doctors and patients so you’d better claim that your drug is precise no matter what it actually means.
• The White Rabbit (@White_Rabbit_OG): When two faces flash rapidly while you fixate, the brain overcorrects for contrast. The illusion is real and unnerving, as is the background music.
• Jack Connor (@Jac5Connor): I’ve watched this at least 30 times. Robot kicks man in the groin. As the post he quotes states, it is a beautiful metaphor for 2025, the year in which humanity got its feet firmly planted in the Ow my Balls! territory.

• Dan Frank: 15 theses on the optimization crisis: or why so many are dissatisfied with society, despite our prosperity. I can but nod along, as I have noted these soul-deadening tendencies myself a few times before. Point number 9 was particularly salient as I read about Robert De Niro’s hotel chains and George Clooney’s old tequila business, perpetuating the cycle of greed and envy.
• David Cain: Maybe the Default Settings Are Too High. An argument for slowing down most things you do, with an emphasis of reading. Pairs nicely with Alan Jacobs’ advice on reading, particularly the second paragraph.
• Andrew Gelman: How much of an NBA team’s won-loss record is from skill and how much is luck? Gelman provides a neat step-by-step account of a statistical exploration which you will appreciate even if you are not a basketball fan. Note his advice on slowing down and thinking about what to expect before performing an analysis. After this you will have an idea of how much the practitioners of journalist science leave out in their final write-ups.
• Steve Dylan: How Gemini Gives Me Hope for a Future Internet. No, not Google’s LLM, but a text-based protocol that reimagines how hypertext on the Internet could work. And if it seems cumbersome compared to even “surfing the web” — let alone mindlessly thumbing down a social feed — well, there lies much of the point!
• Charlie Buckland for BBC Wales: We invited a man into our home at Christmas and he stayed with us for 45 years. Just a feel-good story for the holiday season, to be read slowly and enjoyed.

• Adam Mastroianni: So you wanna de-bog yourself. Mastroianni has a playful way with words that is a joy to read regardless of the topic, but this one in particular fits nicely in the New Year resolution-making season. It is Oliver Burkeman-like advice condensed into shorter snippets, for those who have not yet reached middle age.
• David Allen (or whoever writes his newsletter): The biggest secret about goal setting. Note that there is a big difference between setting your own personal goals and the several steps-removed goals that management gives to their teams. The bit about changing the saliency landscape applies to both.
• Yann LeCun: “the concept (of general intelligence) is compete BS”; the Nobel prize winner Demis Hassabis disagrees. But the fourth paragraph of that rebuttal is precisely what LeCun was talking about (mistaking specific for the general because it has “general” in the name).
• Karl Schroeder: Stop Thinking. ⊕ [Note: ᔥJohn Naughton ] On the difference between “understanding” — which is the analytical method that the people in the rationalist community, LLMs, and Mr. Spock do extremely well — and “reasoning”, which I understand (hah!) to be more akin to Charlie Munger’s mental models, applied intuitively, fluidly, and to the rationalist’s eyes haphazardly. Feel free to apply this distinction to the debate one bullet point above.
• Lily Lynch: Serbia’s Vučić Enters Deeper International Isolation. Could not have happened to a more deserving person! Although of course this means nothing but bad news for my fatherland so I wish El Presidente all the best in the New Year and may what is left of his reign be peaceful if not very long.

• V.H. Belvadi: Working with the end in sight. ⊕ [Note: ᔥPhil Bowell, who also noted the beautiful site design. ] Matches my own experience with Zettelkasten/Slip-box systems, in that none of the very productive people in academia I know actually use anything close to them. Belvadi is sticking to markdown files edited in BBEdit; I am partial to DEVONThink and TinderBox although both of them can also punt text files to BBEdit, which is on my list of should-learn apps.
• Andrej Karpathy: Chemical hygiene. This list of sensible advice for managing our own environment appeared in my RSS reader as part of the Bear blog discovery feed, with small-a “andrej” listed as the author. Since I found myself nodding along to most of it [Note: The risk of chemical exposure while handling paper receipts is overblown unless you work at a cash register, in which case you really should wear gloves. ] I clicked through to check out this andrej’s other work and lo, it was Andrej Karpathy. Unsurprisingly, his 2025 LLM Year in Review was also quite good.
• Brooklyn Gibbs: how to use the internet again: a curriculum. ⊕ [Note: ᔥThought Shrapnel, with a much better re-title. ] Online literacy for adults and children alike. Note in particular that there exist things outside the web: see Project Gemini for an example of a cozy part of the Internet that is very much distinct from the World Wide Web.
• Matthew Haughey: Recent camping and travel discoveries. We will have a fourth-grader in the household next year which means a National Parks pass for the whole family, so this may come in useful!

• Elizabeth Stice: You Think This Machine’s Your Friend, But It’s Not. A reason to rewatch You’ve Got Mail (1998), which I remember as being significantly worse than the movie that inspired it, The Shop Around the Corner (1940). (ᔥJohn Brady)
• Janan Ganesh: When business and democracy don’t mix. Ganesh agrees that capitalism and democracy are in fact at odds, as noted in the last paragraph of this blurb on Enshittification.
• Doc Searls: Shitting Us Not. Similar topic to the above, with a delightful new (to me) word: fecosystem.
• Bryan Vartabedian: Medicine as the last uncompressed profession. On the unmeasurables of medical practice. Of course, medicine is not the last such profession as any live performer can tell you, it is just one of the last ones that is still in demand and for a list of the others still standing I recommend the wikipedia page on Baumol’s cost disease.

• Jacob Savage: The Lost Generation

A story of white male millennials being blocked from career advancement because of DEI. The fields he highlights are scripted television shows, news magazines and academia which aren’t exactly thriving now but per Savage did back when these policies were being implemented (early to mid-2010s). The rise of the “manosphere” and crypto brotherhood was therefore revenge of the jilted, which sounds plausible. One does not become an NFT peddler because they want to but because they couldn’t fulfill their life-long dream of being a tenured Women’s Studies professor.

Note that only early-career positions seem to have been affected, where people with no skill and/or time to choose among many qualified candidates decided to simultaneously switch from one discriminatory heuristic to another. So maybe not everyone should have done it at the same time (a good policy to follow for any change)? Would a method for unbiased selection of early job candidates have to involve an AI? And what are the demographic of OpenAI and Meta’s leadership again?

• Derek Lowe: Where Are They Now: Verge Genomics

A Y Combinator company tries to use machine learning to discover new drugs. No, they didn’t figure it out and are now pivoting to selling pickaxes instead of digging for gold themselves. Godspeed.

• Hiya Jain: A Case Study In Scientific Coordination

Retelling of the story of penicillin’s discovery and mass manufacturing, which is much more complex than the typical serendipity-is-important (or, sometimes, luck-favors-the-prepared-mind) tale that begins and ends with Alexander Fleming’s accidentally contaminating a bacterial culture with mold. This is not to disparage the more popular variant: a big part of my childhood was soaking up wild tales of invention via Discoveries Unlimited which originally came out in the year of my birth but was dubbed to Serbian and played on repeat on state TV in the early 1990s. Of course, my own children now have something infinitely more majestic than the “Video Encyclopedia” from that show… and use it to play Roblox.

• Azhdarchid: Thematic expression in game design, or: Why Dune (1992) rules

This also took me back! And not only because of Dune, which I played several times through the end and liked much more than the sequel, one of the first real-time strategy games. No, this article is also about It came from the desert and Sid Meier’s Pirates! and many other games that used short-but-sweet bursts of different mechanics to tell a coherent story, which is qualitatively different from a collection of mini-games sold to highlight the multi-functionality of Nintendo’s new controller. I hope an indie game studio somewhere is working on bringing them back.

📸 Day 2 of micro.blog’s Winter Wonder Photo Challenge and the word of the day is cozy.

So, here are some cozy web stickers that will make any office cubicle (or — shudders — an open office) hospitable.

• Merriam-Webster: Merriam-Webster’s human editors have chosen ‘slop’ as the 2025 Word of the Year.. A year behind the times, no? Although, same could be said about Oxford’s.
• eryney marrogi: This paper is being interpreted as something it isnt.. The paper in question being about AI-designed super-proteins, with claims of the proteins’ supremacy being somewhat overstated, particularly by the perennial AI alarmist whom Marrogi quote-tweets. Although the thought of humans creating new super-stable proteins by any means, LLM or no LLM, does give me heartburn. Haven’t these people heard of prions?
• Chris Arnade: I just always assumed Oliver Sacks was bullshitting. Hey, I did too, so a profile in The New Yorker to which Arnade refers was no surprise. Caveat lector, always and forever.
• Anil Dash: Cory take decades of fluency in how these systems are broken and serve it up for a mainstream audiences. That’s about Cory Doctorow’s interview for The Daily Show, and I guess I missed the news on Jon Stewart being re-replaced. For a longer pontification from Doctorow, see his conversation with Aaron Bastani.