• 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.

• Ruxandra Teslo and Jack Scannell: To Get More Effective Drugs, We Need More Human Trials. I maintain that this will be nigh-impossible to do in the US until we break the healthcare ouroboros. AI as used now, to increase the number of drug candidates without making a dent in the speed of actually testing them, will only make things worse.
• Benjamin Mazer for The Atlantic: Yes, Some Children May Have Died From COVID Shots. Indeed, and the attempts to say otherwise can only Streisand the issue that should have been just a footnote to the long list of historical vaccine concerns.
• Simon DeDeo: Advice for Early-Career Academics, Part I: Mentorship. No-nonsense advice I wish I had 20-some years ago. I particularly like the distinction between mentors, supporters, fans, friendly elephants and noble adversaries. Left unmentioned are the many people who don’t have your best interest at heart.
• Michael Levy on YouTube: “Hurrian Hymn no. 6” (c.1400BCE) - Ancient Mesopotamian Musical Fragment. The Hurrian songs come not from Mesopotamia but from Ugarit, a city in what is now northern Syria which was one of many victims of the Late Bronze Age collapse. One would hope this would put to rest any questions on whether the humans of that age were like us, but then there are people alive now who don’t think their contemporaries are anything like them.

• Michael DePeau-Wilson for Asimov Press: Why the FDA Is Slow to Remove Drugs. And more importantly, why this is bad. You can’t accelerate drug approvals without also doing more culling on the back end. Symmetry, please.
• James L. Olds: Why Transformational Science Can’t Get Funded: The Einstein Problem. I disagree with most of it, but it is in fact the institutional point of view.
• Anonymous for the Good Science Project: A Top Scientist’s Ideas as to NIH. Did AI write this? Not great, but again, an institutional point of view masquerading as call to reform.
• Bryan Vartabedian: Physician authority and influence. An important distinction, and kudos to Dr. Vartabedian for coping that he has more influence than authority. I, on the other hand, have neither.
• Joe Boudreau: On 10 Years of Writing a Blog Nobody Reads. I have been doing it for at least 15 (13 of those in English) and it is in fact wonderful.
• Todd Vaziri: The “Mad Men” in 4K on HBO Max Debacle. The best and most concise review of this royal screwup of one of my favorite shows.

“The internet is dying on the outside but growing on the inside”, wrote Yancey Strickler last month in a follow-up to his 2019 essay The Dark Forest Theory of the Internet. To avoid misunderstanding, malicious interpretation, competitive intelligence gathering and cancelation, conversations have been moving from the public-facing “social” “media” to gated, invitation-only services (e.g., your favorite Substack author’s members-only discussion forum) and private group chats (e.g., the Let’s Bomb Yemen Signal texts).

But some parts of this Cozy Web are growing faster than others, and as if often the case doctors and scientists are ruled by inertia. Both groups have the perfect setup, in the form of professional societies, to carve off some gated space in which to have potentially controversial discussions without providing fodder to “the enemy”. ⊕ In these kinds of metaphors I always reach out to Venkatesh Rao’s The Internet of Beefs, which explains quite well why the public Internet has turned into a dark forest in the first place. And yet even the most developed online community program I know of — American Society of Clinical Oncology’s myConnection — is a stuffy, ⊕ ASCO boasts as having more than 50,000 members. The two largest “communities” on MyConnection, “New Member” and “Women in Oncology”, have more than 9,000 members each yet the last post on one was 9 days ago (with zero replies) and 7 days ago (two replies). All of November, the more active WiO group had 9 posts with median 1 reply (range 0–20). formal messaging board that can barely be considered active. Most of ASCO’s online activity is still on X, where the official account has almost 150,000 followers and the hashtag for its annual meeting is heavily promoted. Other large hematology/oncology societies like ASH (hematology) and AACR (general cancer research) don’t even have that. Their “online community” is a member directory and heavy promotion of in-person conferences, which I can only assume are the true money-makers.

So I have to wonder, do they still deserve to call themselves “societies”? It is, after all, 2025 and much of life has moved online. By not providing an avenue for true internal discussion and instead promoting public debate, are they hurting their members' cause more than helping? ⊕ Yes, it was fun to post out in public when there was a slight chance that your favorite celebrity — or the POTUS — would retweet your post, but we have since learned that this is a liability more than a benefit and there are more high-follower accounts on X now that I would rather avoid. I have argued recently that scientists may want to button up their conversations if they are to keep or regain trust. Should these societies not be providing the means to do so, and not only once per year in a stuffy conference room? ASCO’s MyConection is on the right track, but much too formal. Yes, give people the opportunity to create subgroups and even more private chats as you do now. But if you think debating on X with millions of spectators is healthy, why not give all 50,000-plus members a chance to interact by default, and do so in a format that is not an early 2000s web forum?

Concluding the most recent article, Yancey Strickler provided a toolbox for people to create their own communities which he called the Dark Forest OS, of DFOS. While laudable, this effort is to put it bluntly too artsy fartsy for me. Strickler comes from the world of “creators” whose sensibilities are much different from those of doctors and scientists. But then science and medicine already have much of DFOS in place, from a members list to paying dues. The only thing we need now is for the said societies to build their walled gardens — with an app included! — which they would promote instead of X at the annual meetings and other conferences.

Where a SciMeDFOS would come useful is at smaller scale, for collaborative groups and maybe even large individual labs, where members are known but there are no dues, funds, or IT workers ready to build a custom Twitter clone. If I were to make one now I would probably use Hometown, which is a fork of Mastodon that enables local-only posting, though it being a single person’s passion project makes me a bit reluctant. But then what else do we have, Discord, WhatsApp and Signal? Whatever Dave Winer comes up with in collaboration with Wordpress? Maybe Squarspace could make creating private Twitter clones be as easy as creating websites? I will be on the lookout.

• Rachael Bedard: I Went to an Anti-Vaccine Conference. Medicine Is in Trouble. Tragic considering all the good vaccines have brought us, most recently against cervical cancer. And the news from the FDA is, of course, a disaster from any perspective.
• Kurt Streeter: How to Fix a Typewriter and Your Life. A palate-cleanser for the above. And if this piques your interest, Chris Aldrich has a wonderful primer on learning typewriter maintenance and repair.
• Ross Douthat interviews Paul Kingsnorth: ‘This Is the War Against Human Nature’. Not the only interesting interview Dothat made, and they make for better reading than listening.
• Jeff Giles: How I Began to Love Reading Again. I too loved If on a winter’s night…

Enjoy!

Today I learned, thanks to a leaked email from Vinay Prasad to his staff, ⊕ I also learned that Prasad puts a double space after each period which is inexcusable in 2025 when we all use variable fonts on our electronic devices, not a fixed width-font typewriter. Whatever his high school typing teacher told him, he should drop the habit.that FDA’s CBER does actual bench research. This is pure stupidity on my part, as it is right there in the name: Center for Biologics Evaluation and Research. Silly me. They have a page dedicated to describing the work of their 65 principal investigators, and it seems to be at least on par in topics and rigor to the work done at the NIH Intramural Research Program though the latter if of course bigger.

Prasad’s email boils down to this: CBER research staff has strayed from its mission, which is primarily regulatory. We will look at work performed and planned and cut that which is not in line with the mission. He invokes sunken cost fallacy by name, so one would assume work in progress will also be cut, maybe even things completed that haven’t yet been written up — why spend hours formatting a manuscript when you could be reviewing IND Investigational New Drug applications and BLAs Biologics License Application, and let me use this sidebar to note how infuriating it is that one acronym includes the word “application” in it and the other doesn’t, forcing one to resort to clumsy phrases such as the one to the left. I supposed you could write “BLAs and IND applications” but that is listing them out of sequence. instead? And we certainly shouldn’t abuse the privilege of conducting research without having to apply for grants by just padding our CVs with insignificant work that will never be cited, which is another thing Prasad rises against.

My initial reaction was “damn right” but then I realized that regulatory review is just another price scientists-at-heart pay in order to do the work they want, similar to teaching in academia and low pay with no opportunity for outside activities at the NIH IRP. I suppose that eliminating the opportunity for self-directed research — which is what Prasad proposes instead of, let’s say, cutting it down to 10–20% of one’s time — would select for a certain type of a person (I imagine a box-checking blankface) but is that what we want? Is that what Prasad wants?

The tedious and unappreciated work of regulatory review is the price some scientists are willing to pay in order to perform research. Giving scientists the opportunity to do the work that’s meaningful to them is the price the FDA may have to pay to get good people to perform regulatory review. Any important scientific contributions that arise from this concession should be seen as an unexpected gift, not a requirement for staying employed as a reviewer.

• Tom Forsyth on Mastodon: “Recent discussion about the perils of doors in gamedev reminded me of a bug caused by a door in a game you may have heard of called Half Life 2.” Parallels in biology immediately come to mind.
• David Roberts on Blue Sky: “In an era filled with tech dipshits who never developed emotionally past the age of 13 & use their wealth to become odious monsters … listen to Steve Wozniak.” We are where we are in big part because there weren’t enough Steve Wonziaks in key industries when it mattered. Or rather, because they by definition bowed out and gave the sociopaths free space to roam.
• Ruxandra Teslo on X: “We should do smth abt this.” The “this” is the threat of clinical trial infrastructure being flooded by the biotech equivalent of AI slop. And many misguided people think that this is a good thing!
• Joe Janizek on Substack: The birth of Advanced Radiology. Or: radiology as chess. Radiology and pathology are the few areas of medicine in which AI may be produce immediate benefit.
• Nassim Taleb on Substack: Medical Mistakes with Probability, 2. Why the benefit of statins in people with barely elevated cholesterol and no other risk factors is grossly overestimated. Note that this constitutes most of the market for statins! My cynical take: Now that they are all out of patent I don’t think anyone would complain about cutting back.

When I wrote that opening up science and increasing trust in it are mutually opposed goals, I didn’t imagine the perfect example would come up so soon in both the thing that happened and the commentary about the thing. It is helpful, when interpreting what follows, to keep in mind CS Lewis’s lecture on The Inner Ring with the following two adjustments: there are in fact many rings, concentric, with people ordered in them according to some gradient; and although academia has the secret rings Lewis talks about there are also many public ones with members known, where the innermost ring to a high degree overlaps with Harvard.

The first thing that happened was a segment on 60 Minutes, America’s premier newstainment show, about the current administration’s defunding of Harvard and the implications for science. A few scientists gave interviews, including a bench researcher whose lab studied “different aspects of cancer biology, including tumor heterogeneity, cell-cell interactions, tumor microenvironment, cancer metabolism, drug resistance, and cell signaling.” So, very much a “cancer researcher”, though as far removed from the practical aspects of cancer management as you can imagine. Still, from applying for grants to writing up research results for peer-reviewed journals, scientists have been conditioned to tie whatever they are doing to real-life, practical applications: in the interview Dr Brugge said what she and her post-docs must have written hundreds of times before, that her work has the potential to prevent breast cancer.

There is a legitimate discussion to be had about overblown claims to practicality. The debate has in fact been ongoing for decades now in the editorial pages of various scientific journals. But then someone formerly of Harvard, then Duke, then out of academia completely after a legal dispute, wrote about the issue in light of the segment. This is the second thing that happened.

The article for the most part lists personal observations about the two scientists interviewed for the segment (the second was David Liu, about whom the authors had kinder words). It very much had the sound of someone expelled from the circle grinding an ax with the inner ring. This led to even its salient observations being framed somewhat maliciously. For example:

Universities and their faculty have learned that success in today’s system depends not as much on actually doing science but on marketing the perception of science — framing even routine findings as lifesaving advances. “Cancer” has become a brand, a universal justification for more funding and prestige. The public sees heroism; insiders see dollar signs. One of the strangest features of this ecosystem is how many researchers who do pure basic science — work with no foreseeable medical application — nevertheless frame their research as “curing cancer.”

Which goes from pure speculation to undisputable fact. The need to frame everything as “curing cancer” stems from all the money being allocated to cancer research. It is all about the incentives: Willie Sutton robbed banks because “that’s where the money was” and scientists are no different.

But did I just, even in this gentler framing, compare scientists to bank robbers? See, this is why the debate is best held behind closed doors, lest a politician uses the fact that most research findings are false as an excuse to cut funding. This is what most comments to [Mike

This is the open science dilemma: have the debate out in the open and risk providing ammunition to your enemies? Or do it behind closed doors and risk mistrust? A few decades ago the point was moot as the “enemies” were first powerless hippies, then only slightly more empowered religious zealots. As we all know, the anti-science front has since strengthen. Why that is, well, that is yet another debate. Since one of the reasons is that many scientists openly picked sides, whether out of conviction or out of fear from being ostracized, this is also a debate best held behind closed doors.

Until that happens, we will continue to have dialogues such as this one, ⊕ The link is to what I think is the final post in the back-and-forth, which I think is the only guaranteed way to show the entire thread, but X truly wasn’t built for sharing these kinds of interactions and is not the best medium for having them. all in support of the beef-industrial complex. Other fields have already wised up: the Internet is dying on the outside but growing on the inside, with important conversations moving to private forums. Which, as I argued, they should.

After citing Niko McCarty’s list of 30 biomedical essays yesterday, I had an urge to find each and have a separate post linking to them. Well, good thing I procrastinated because he just came out with an ever longer list (130 and counting) that does have the links. Still no Mansions of straw…, but I’ve just asked asked him to consider adding it so let’s see how the list evolves.

• Niko McCarty: Here are 30 great essays about biology. They are indeed great, and it even includes one where I gave a modest and unattributed contribution (you will be able to guess which one). To this I would add William Kaelin’s Publish houses of brick, not mansions of straw, cited many times on this blog (most recently just last month).
• Jason Locasale: My latest article in The National Review on what 60 Minutes got wrong about Harvard and the biomedical research industrial complex, and why the deeper issues in science can’t be fixed by throwing more money at broken institutions. Here is the article, which I agreed with directionally but had so many “I know this person and let me tell you what they are truly like” moments that I thought there had to be a backstory to this insider-ish scoop. And indeed there was, as noted in responses to Michael Eisen’s tweet. So much drama, and all it does is make it easier for people to shrug their shoulders, say that it’s complicated, and defer to higher authorities (i.e., Harvard).
• Nassim Taleb: I believe this paper addresses, even solves, the most relevant statistical problem of the century, including the replication crisis & the fake results in publication. No false modesty here. Papers like this make me think that frequentist statistics are fine for the lab where you can truly do the same experiment over and over, but when it comes to clinical trials you can never cross the same river twice and we should all be Bayesians.
• Christopher Hooks: I sincerely believe that anyone pushing this should be shot. I agree in spirit. Whoever made this AI abomination should study Hayao Miyazaki and his work.