Now that I am back in clinic full-time I have tried and failed to pick up on the more clinical podcasts. Both ASCO and ASH have their podcast series, but they are all so formal and scripted you can see the teleprompter scrolling in front of the speakers’ eyes.

One potentially bright note could have been Cancer Stories, which are spoken versions of Journal of Clinical Oncology’s Art of Oncology article series. Note the past tense; I have a longstanding antipathy towards “narrative medicine”, a mode of fiction in which doctors combine patient stories, or present a single patient’s story anonymously, to make a point. The fallen king of narrative medicine was the neurologist Oliver Sacks, and look at how that turned out. Social media are of course an even more fertile ground for this kind of fakery; I won’t go into the X, Bluesky, Mastodon, TikTok and YouTube accounts that are completely full of it, but there is a lot of content out there and all of it — all of it — is bullshit.

So I was hoping that these stories being published in a peer-reviewed journal would at least be closer to the truth. And I’m not saying they are not, an inch or two closer, with cases not being invented out of whole cloth. What I am saying is that JCO editors are incapable of recognizing AI slop and the very first story I listened to was full of it.

It was disconcerting to hear a professional voice narrate The Liver We Share in the April edition of the podcast. In the story, BU medical student Ryan Wexler writes about his experience as a living donor to his then-fiance now-wife who needed a new liver. Quoth Wexler: “When I learned I was a match, relief arrived not as joy, but as quiet permission to hope.” The hope was justified, for everything went well: “Her recovery, and our journey as a whole, bears little resemblance to the decisive triumph I once imagined. It is quieter, ongoing, and more powerful for it.” Yes, yes, so much quiet. Other empty metaphors and nonsensical turns of phrase abound.

Did Wexler feel bad, I wondered, when the completely credulous host and a great hematologist Mikkael Sekeres — a pre-AI book author I should add — asked him probing questions about his mental state and the specific words he used in the essay? Couldn’t you see through the AI bullshit, Mikkael, I wanted to scream out. He is a bit older than me so maybe there is an age cutoff at which people can no longer detect the slop? At least one of my parents and one in-law don’t have a clue, as they keep forwarding sloppy Instagram links despite my not having an account for more than a decade.

In any case, no, peer review is no protection against bullshit and I will not be exposing myself to any more of it. End of rant.

Derek Lowe is scandalized by the fact that 9 out of 10 drugs that get to a first-in-human trial don’t get approval or, to use some jargon, a clinical failure rate (CFR) of 91% per year. He quotes a recent paper which followed CFR over the last six decades ⊕ [Note: Just to make things confusing, the paper itself calls this percentage “clinical attrition” but Lowe rebrands it to a CFR. Let’s for the sake of consistency stick with the latter, although a pedant may question whether that statistic truly is a rate. ] and noted that it was improved somewhat in the 1970s and 1980s — down to about 80% — but was consistently at or above 88% in every other decade analyzed.

Both the paper and Lowe present this as a Bad Thing. Here is a direct quote from Lowe:

But let’s think about that 91% failure rate for a moment. When I bring this up in presentations, I invite the audience to consider what the auto industry would look like if 91% of new car designs proved unable to roll out of the factory, or if 91% of new airliner models were unable to leave the ground - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them. No cutting-edge restaurant could survive if 91% of its innovative dishes proved inedible or outright poisonous. What other industries operate under these bizarre conditions?

Sounds scary! The paper has a different and a somewhat less alarming spin: see how bad our preclinical testing is if so many of the drug candidates don’t make it to approval for reasons of biology. If there are bad side effects, or the drug doesn’t make it to the targeted tissue, or the liver destroys it too quickly, should we not have picked that up in cell culture or animal testing? Should we not focus our resources on developing more human-relevant preclinical tools, and maybe call them New Approach Methodologies (NAMs)?

At this point in the story I should mention that the paper in question, titled “Need for NAMs: A systematic evidence synthesis revealing over half a century of drug development failure”, was published in NAM Journal. Holy motivated reasoning, Batman.

So now let’s look at the counterfactual: what if the increased CFRs from 1980s to today came by design, from the realization by drug developers that preclinical testing isn’t the greatest at predicting toxicity and is completely useless when it comes to efficacy, so why not just get drugs to clinical as quickly as possible and be as quick in cutting them? My go-to paper outlining this philosophy is one from 2010 which a team from Eli Lilly — as successful at developing drugs as they come — published in Nature Reviews Drug Discovery. To pick out two key points from their above-the-paywall outline:

Reducing late-stage (Phase II and III) attrition rates and cycle times during drug development are among the key requirements for improving R&D productivity.

To achieve the necessary increase in R&D productivity, R&D investments, both financial and intellectual, must be focused on the ‘sweet spot’ of drug discovery and early clinical development, from target selection to clinical proof-of-concept.

Which is to say: since Phase II and especially Phase III trials are an order of magnitude more expensive than Phase Is, let’s quickly do what we must to get drugs into clinic, gather early human data, then make an informed decision. If that makes an arbitrary number go up, so be it.

You can see why the de-emphasis of preclinical efficacy data could have made some lab people unhappy, which I guess is why we now have a journal called NAM. Or was it ‘Nam?

Of course, there are tradeoffs everywhere, and the big tradeoff in the “fail fast” school of drug development is that you are tying your faith, financial and otherwise, to the health care system and contributing to the health care ouroboros. The one where Americans pay so much for health care because drugs are so expensive to develop, and drugs are so expensive to develop because health care in America is generally so expensive. But of course, no one is obligated to run their early-stage trials in the US.

Vinay Prasad asks whether health care is a human right and, using some convoluted mental gymnastics, answers no with a disturbingly LLM-like turn of phrase:

Health care, as it is practiced in 2026 America, is not a human right. It’s a tax penalty on our ignorance and wishful thinking.

This is bullshit, in the classical sense. Not to psychoanalyze Vinay ⊕ [Note: The house style over here at Infinite Regress is to default to last names for any and all persons mentioned. I will on occasion make an exception for friends, which is indeed the case here. ] but this is what years of pandering to your ticket-paying audience will do to you: lose common sense.

To be pedantic, the Universal Declaration of Human Rights specifically mentions the right to health, i.e., a minimum standard of health to which everyone is entitled. The minimum standard in America is prescribed by a single law, EMTALA, which guarantees the right to emergency treatment for those who seek it. It is a floor low enough to qualify as a basement — pathetic for one of the richest nations in the world — but it is nevertheless a floor. Should the minimal standard also involve immunization and the few disease screening programs that are known to be beneficial? Yes! But they are not yet a right in the US. As I’ve noted before, I don’t think it should include the largely superfluous annual “wellness visits”. But if that’s what it takes for immunizations and screening to happen, fine.

But that’s not the bee in Vinay’s bonnet. Rather, he takes issue with the totality of American health care — who doesn’t? — and makes the case for that particular Lovecraftian horror not being a human right. Well, duh.

Cthulhuian or not, there is one good thing about the system: its extraordinarily high ceiling. This is still the place to be for getting the latest and greatest medical treatment, whether in a large academic medical center or a small community hospital, contingent on the doctors in either place knowing what they’re doing. Most stories Americans tell of their exposure to European health care are about how quickly and cheaply minor procedures are performed. Not told are stories of patients with metastatic cancer or autoimmune disease who are waitlisted for getting immunotherapy or other biologics. Or those with debilitating arthritis waiting months for a hip replacement.

With the high ceiling comes some extra girth in the middle, where there are many unnecessary treatments given and diagnostic procedures performed that Vinay rallies against. For good reason! But how you come from Ending Medical Reversal to proclaiming that health care is not a human right is beyond my comprehension.

• Vinay Prasad: The Future of Medicine. Extrapolating the modern tendencies of removing humans from the equation, Prasad (unintentionally?) presents a bleak scenario indeed. For a reality check, here is Cory Doctorow.
• The anonymous Slime Mold Time Mold author: You Can Discover the Drives. An interesting analogy between human drives — from the basics like thirst and hunger to the more complex ones like the need for recognition — and chemical elements.
• Chris Good: Not your keys, not your songs. Remember web3, which tried to be the asbestos we are putting into our technology until “AI” came along? Here is the aftermath of some well-meaning people trying to dabble in it. It did not end well.
• Brett & Kate McKay: How to Recognize and Deal With High-Conflict People. Recognition is important; dealing with them is usually straightforward: flee. And for the times that you can’t — these people need doctors too! — there is some good advice at the bottom.

After 16 years of successfully avoiding Epic*, tomorrow is the day: my provider** training begins. Let’s see how it compares to Cerner, Allscripts et al.

• Fairly certain text behind the link is partially AI-generated, but the illustrations are good!

** Hate hate hate that term.

• Tristan Manalac for Biospace: Amgen’s Tavneos troubles continue as NEJM retracts pivotal publication. First came FDA questions about data integrity. Now the academic authors are confirming the data tampering, though per the now retracted study they did “vouch for the completeness and accuracy of the data, the complete reporting of adverse events, and the adherence of the trial to the protocol. All the authors participated with the sponsor in the design of the trial, the analysis of the data, and the writing of the manuscript.” I wonder if people who sold this rotten pile of garbage to Amgen will offer a refund. So it goes…
• Carl Zimmer and Marco Hernandez for The NYT: This Cell Feeds, Grows and Reproduces. And It’s Manmade. “Dr. Adamala named her creation SpudCell, after its potato-like appearance. Rather than patent it, she and Dr. Endy are organizing a community of scientists to focus on making SpudCells more fully alive and adapting them to new kinds of experiments.” Bravo! Maybe science isn’t a complete lost cause.
• M Auerbach, MY Lim, GM Rodgers, and T DeLoughery for Sensible Medicine: When Normal Isn’t Normal: Non-anemic Iron Deficiency. A very academic group of authors makes a very good case for treating low iron levels in the absence of overt anemia. This is in response to an earlier text which poo-pooed the practice as “overmedicalizing normality”. Adam Cifu from Sensible Medicine proposes randomized controlled trials, though if symptoms of low iron are as diverse as restless leg syndrome, “brain fog” and craving for ice it would be a challenging endpoint to establish. Boy, isn’t medicine hard.
• Titotal (pseud): The best cause will disappoint you: An intro to the optimisers curse. ⊕ [Note: ᔥAndrew Gelman ] Mathematical demonstration of why effective altruists are, at the end of the day, a bunch of bozos. And not just them: America is the land of hyperoptimizers and if Taleb’s Incerto wasn’t a convincing enough case for why that doesn’t end up well in the long run, well, here is a much shorter Substack post that shows one facet of the problem.
• Ed Conway: The Apple-Banana Paradox. On the incredible flattening of banana prices in the last 25 years, and the incoming threat of another fungal infection that could wipe out the current Cavendish banana monoculture. On the other, could this be an opening for a Honeycrisp of bananas? One can hope.

• Max Kozlov for Nature: Inside the new political screening that’s stalling NIH grants. The plot to murder American science in the style of Rasputin (poisoned, shot, shot again) is well under way, and this is the slow-release poison. Choke off funding, dissuade people from thinking about federal funding, see the number of scientists drop for years to come.
• Vinay Prasad: Marc Tessier-Lavigne and Jose Baselga. To be clear, there are many things wrong with American science and Prasad in his review of the book How To Rule the World presents some good examples, but you don’t treat a serious diagnosis by killing the patient.
• Andrew Gelman: Bayesian Workflow exists as a physical book! An example of what’s right in science. I will be ordering a copy.
• Ann Lee for the Guardian: ‘David Bowie was a crazy workaholic’: Labyrinth at 40 – an oral history. ⊕ [Note: ᔥBill Harris ] An oral history done the right way, about a genius person in a genius movie.
• Catherine Ruth Pakaluk for The NYT: Life Is Better With Siblings. Sure is — just ask Jennifer Connelly from The Labyrinth! Joking aside, this is a serious case for large families and one with which I largely agree, though the double-digit census of children in some of the families mentioned gave me pause. [Note: The old George Carlin bit about idiots and maniacs applies. ] Regardless, for most people the right number is greater than two, and for almost everyone it is certainly greater than zero.

• Keller, Murray, Ivory & Cabreros for The NYT: The Deadly Rise of Giant Trucks and S.U.V.s. A beautifully-illustrated case for America’s king-sized vehicles being the main culprit for increased pedestrian deaths. The careful reader will remember that this “Big SUV hypothesis” was also highlighted by Brian Potter a while back, though it didn’t explain all of the increase. And of course my conspiracy theory may also be true, although if there are people who said a while back “hey, these big A-pillar will lead to more pedestrian deaths” and then there are more pedestrian deaths, well, there’s a conspiracy theory for you.
• Adam Cifu: Advice for Internship. July already? Seems like my last day of residency was but a few years ago, but now, it’s been a full dozen years as of today. And I’ve given up sharing tips almost as long ago.
• Casey Handmer: In Defense of the Marginal Baby. Handmer presents the case for having more babies, with which I agree wholeheartedly. I do not share his enthusiasm for a contraption some call a “Snoo”, a preposterous subscription-based baby rocker.
• Charlie Stross: The Golden Age Of (sic!) Bond Villains. Stross shares the afterword for a reprint of his book The Jennifer Morgue, which is about a billionaire who wants to unleash a Lovecraftian horror in order to rule the world. It was written in 2009 and yes, some idiot billionaire — probably one from the Dialog crowd — must have confused it for an instruction manual. Anyway, Stross’ “Interview with the Entrepreneur”, the entrepreneur in question being Bond arch-nemesis Ernst Stavro Blofeld, is a thing of beauty.
• Ian Finder: UHF X11. A beautifully pixelated window system built for visionOS and Apple Vision Pro. Due to my newfound aversion to Apple I haven’t touched my own AVP in almost a year. This has persuaded me to pick it up again, for the novelty if nothing else.

Yesterday, I received the strangest of emails. It was nominally from the founder of a physician services company, one of those that will, for an undisclosed “signature membership” fee, help doctors with contract negotiation, financial planning, estate management and such. Fine. Stylistically I doubt that the founder, or indeed any human, has had much input on the contents, which were this: sign up for a free 3-day online course and your host, an “expert on lead generation and trust-building” will teach you how to increase revenue and influence in order to get more patients to your clinic. He once, and I am quoting directly from the email here, “helped a little-known surgeon go viral, ⊕ [Note: This is most likely a reference to John P. Williams, a breast cancer surgeon and the creator of the YouTube channel Breast Cancer School for Patients. He was the chair for two and a half years. ] fill his waiting room, and become the White House–appointed chairman of the President’s Cancer Panel.”

Crikey.

This gave me flashbacks from October 2023 when the annual meeting of a medical society which looked more like a TED talk than a serious clinical conference shook me so much that I wrote about it. Yes, of course doctors should learn to become influencers, as well as entrepreneurs and art critics, and also counselors on the matters of faith, car safety and gun violence, everything — everything! — but experts in medicine, which up until 1986 encompassed “the science and practice of caring for patients and [various aspects of] their injury or disease”, but then in the 1970s and 80s, all diseases apparently eradicated and injuries no longer needing treatment, started to include health promotion. And who can possibly be against promoting health?

Something else lamentable happened a half-century ago: in 1975, “the Federal Trade Commission (FTC) accused the profession of ‘restraint of trade’ and legally persuaded doctors to permit advertising amongst their clan”, as noted in the Journal of Medical Ethics. Yes, you have read that right: under threat of legal action, doctors were persuaded to advertise. Up until then, the Code of Ethics of the American Medical Association explicitly forbade it, those 19th century idiots not knowing what was good for them. Or their business. Is there a difference?

Let me postulate that, prior to that faithful — or was it faithless? — decade, the medical profession was defined as sharply as a scalpel and doctors had a notably different status from other professions. Justifiably so, was it not, for people who asked you about bowel movements and sexual habits, and poked and prodded various bodily orifices. [Note: Ah, but I wrote this sentence in the past tense, for both probing questions and the actual probing are done less and less in doctor’s offices, unless it is probing with an intravenous needle to inject that expensive drug, or to insert a medical device. Note how more of the former probing would have led to less of the latter. ] With an increase in scope, the equation of medicine to a business like any other, and one grave of an old physician at a time, the profession has slowly been getting blurrier. So blurry, in fact, that one can exclaim how “there is nothing wrong with healthcare that getting rid of doctors won’t fix” at a tech summit keynoted by Tony Blair ⊕ [Note: ↬John Naughton ] and get applause instead of jeers. So blurry, are they not, that they are just asking to be rubbed out!

Was there a master plan to eliminate a profession and make it into an ordinary trade? I doubt it. It was, as ever with Americans, a pinch of short-term gain and a dash of performance artistry in the stew of unintended consequences. But how oh how to unstew it now?

As seen in the official email communication from the American Society of Hematology:

Milos, if you’re sitting for the hematology boards this November, you don’t just need more resources — you need a structured plan that fits alongside your fellowship and life.

AI slop is the clipart of our age. This too shall pass, one would hope.