Apart from looking like he has just been on the losing end of a fistfight, and having occasional bouts of nausea, Ben Sasse seems to be doing as well as someone recently diagnosed with metastatic pancreatic cancer possibly could. Both the nausea and his face peeling off are because of daraxonrasib, a new drug which targets KRAS G12 mutations which are common in many cancers but are found in most pancreatic ductal adenocarcinoma (PDAC). As a reminder, PDAC is the one that Steve Jobs did not have, the one that has the dubious distinction of being both the most common and the most lethal cancer of the pancreas.

Well, daraxonrasib seems to be doing its job and doing it well, based on a company press release. Remember, most press releases should not count as evidence for anything. This particular one, however, is worth reading because it is (1) for a randomized controlled trial with (2) a “hard” endpoint of overall survival ⊕ OK, putting my pedant hat on, the pre-specified co-primary endpoints are progression-free survival (PFS) and overall survival (OS) in the RAS G12-mutant population. What is reported in the press release is only OS in the “intent-to-treat” which is to say both G12-mutant and wild type populations, which was a secondary endpoint. A bullet point at the beginning says that all primary and key secondary endpoints were met, so why not report both? Probably because one looked better than the other, but would it not be a tad suspicious that a less targeted population did better than the more targeted one? But this is just speculation, let’s see review the actual data once they come out. which will (3) be presented at the ASCO annual meeting, I imagine as a plenary talk, in early June of this year. The thing to look for there will be informative censoring, in particular early censoring of frail participants — the ones more likely to die early of their disease — who were randomized to receive daraxonrasib but then withdrew due to the “manageable” toxicity of a melting face. The fact that there are no participant numbers reported at all in the release makes me suspicious, though information on the number of patients enrolled is readily available: 501. That’s a lot of patients!

The company is certainly feeling optimistic: they have already received a National Priority Voucher from the US FDA and will now submit a New Drug Application. Kudos and congrats for designing and testing a working drug without using AI, because to read both professional and lay media the past two years it is a miracle there were any drugs being discovered until Large Language Models came along.

Yes, I had to invoke AI, because it is becoming exceedingly common for people to give algorithms credit where it is not due. This is what Tyler Cowen wrote yesterday about pancreatic cancer research:

AI and the pancreatic vaccine. More testing is needed, but there is a reasonable chance that we have a good treatment for pancreatic cancer, and AI was instrumental in that. It is mRNA as well, so a double burn on the haters.

The link is to a post on X by one Rotimi Adeoye, a “contributing opinion writer @nytimes” (one guest essay as of today which is one more than I have so congratulations, I guess?) who in true X fashion superimposed a screenshot from an uncredited journal abstract over someone posting a link to an NBC news article about the updated results of a phase 1 trial of an mRNA vaccine for pancreatic cancer. ⊕ For those not keeping track, you are right now reading a blog post about a blog post about a retweet of a tweet about a news article based on a press release. You’re welcome. These were presented yesterday at the annual meeting of the American Association for Cancer Research but were hinted at in a press release (?) from Memorial Sloan Kettering, where the vaccine — generic name autogene cevumeran which rolls right off the tongue doesn’t it? — was being tested.

Remember how a few paragraphs above I had implied that you should ignore most press releases? Well, news on academic websites should rank even lower as no one there has to answer to the SEC. The primary study was great for what it was, a first-in-human trial with laboratory endpoints meant to test whether the participants’ immune system responded at all to the vaccine. And it seems that it did, as shown in not one but two papers in Nature published two years apart. The number of original participants, all of whom had early-stage, freshly resected and otherwise untreated PDAC upon enrollment, was 19. Three of these did not make it to the vaccine as they had progression, died, or had toxicity from adjuvant chemotherapy before being dosed. Chemotherapy? Yes, in addition to the vaccine everyone also received “adjuvant” (meaning: there to “clean up” any residual cancer after surgery) chemotherapy (FOLFIRINOX, not for the faint of heart) and immunotherapy (atezolizumab which is in comparison to the chemo a walk in the park but even that has its side effects). There was no control.

Of the 16 participants, 8 were “responders” to the vaccine as measured by some highly sophisticated laboratory tests — not that the patients would care what their blood work showed — and in 7 of those the cancer hasn’t come back for 3 years as noted in the follow-up Nature paper or for 4-6 years as noted in yesterday’s update. This compares to 2 of 8 who were “non-responders” to the vaccine.

If you don’t have your calculator handy let me do the math for you: 9 of 16 patients, or 56.25%, with newly resected PDAC who received chemotherapy, immunotherapy and the vaccine were still alive more than 3 years after treatment. You may not know this, and I didn’t until I looked it up just now as it has been a while since I have treated patients with newly diagnosed early-stage pancreatic cancer, but the median OS after (modified) FOLFIRINOX alone in a recent large, randomized Phase 3 trial was 53.5 months, with 43.2% of patients still alive 5 or more years. Did the addition of atezolizumab and the vaccine change anything? I can’t tell and neither can anyone else until there is a randomized controlled trial, which isn’t to cast shade on the investigators — kudos to them as well for a successful first-in-human study — but let’s curb our enthusiasm.

So we have some updated results from a tiny trial that didn’t really move the needle one way or another, and yet Cowen et al. feel the need to push AI into the narrative. To be clear, there is absolutely no mention of LLMs, machine learning, algorithms or artificial intelligence of any kind anywhere in the autogene cevumeran literature. Granted, it is a “personalized” vaccine, meaning that every potential participant had their tumor sequenced and up to 20 vaccine targets identified among the newly mutated proteins. I am sure there was a lot of computation involved. But not every sophisticated computer analysis is AI, let alone an LLM, so I truly don’t see how they could legitimately be brought into the conversation.

And in case you were wondering, no, the screenshotted abstract did not in fact back up Adeoye’s claim. Best as I can tell this was the paper in question, a speculative review article in an obscure journal written by a Shanghai-affiliated group of authors who had nothing to do with BioNTech whose purpose was to be a never-looked-at reference for a false claim, that “AI played a critical role in advancing the vaccine”. Anything for the clicks, am I right?

Adeoye’s behavior was regrettable but Cowen’s is detestable, especially when paired with his look-at-the-sheeple attitude towards humans. ⊕ The linked to article from Cowen is particularly wrongheaded if you realize who the Luddites really were and that the label should in fact be a positive one. Cory Doctorow had warned about AI companies over-promising their capabilities for a short-term gain. But they don’t really need to: there are plenty of useful fools willing to promise on their behalf, giving it credit even where there is none.

Infinite Regress is not a professional outlet yet even this here half-brained bozo knows better than to mix fonts in a single word. They should have shaved off the “ć” to a “c” if their house headline typeface didn’t have the right diacritic, but then why doesn’t it?

And hey, congrats to Denver!

Cory Doctorow wrote this morning about a short-lived business venture of his from the late 1990s that, during a brainstorming session, invented SEO slop years before either of those two terms became widely known. That train of thought didn’t go anywhere — they weren’t sociopaths — but it made him realize an important life fact:

The point of this is that there were lots of people back then who had the capacity to imagine the kind of gross stuff that Zuckerberg, Musk, and innumerable other scammers, hustlers and creeps got up to on the web. The thing that distinguished these monsters wasn’t their genius – it was their callousness. When we brainstormed ways to break the internet, we felt scared and were inspired to try to save it. When they brainstormed ways to break the internet, they created pitch-decks.

Apple is another clear example. The book Apple in China opened my eyes to the ruthlessness with which their operations team worked throughout the company’s history. Small wonder then that elevating their Chief Operating Officer to the CEO role would lead company valuation to skyrocket and its culture to decay so much that it got an introverted nerd to write an open letter to the presumptive CEO futurus.

And of course we have the modern-day King of the Sociopaths in Sam Altman. I have decided not to read anything that is longer than 10,000 words this week unless written by Philip K. Dick so I did not delve into The New Yorker account of Altman’s adventures in bullshitting, but John Gruber has helpfully provided some excerpts. Behold a quote from an OpenAI board member:

“He has two traits that are almost never seen in the same person. The first is a strong desire to please people, to be liked in any given interaction. The second is almost a sociopathic lack of concern for the consequences that may come from deceiving someone.”

Point number one is on display at any of his interviews. One of the last episodes of Conversations with Tyler I listened to was with Sam Altman and the extent to which he reflexively and without thinking agreed with every possible hypothesis and conjecture Cowen put out was comical. Point number two makes him exceedingly dangerous. That so many luminaries of big tech are willing to hold hands with the man and continue doing business with him is Wittgenstein’s ruler of Silicon Valley sociopathy.

The problem isn’t that sociopaths exist — they always have — but that the casinofication of the American economy has created outsized rewards for those particular personality traits while pushing away people with stronger ties to reality. Once a field attracts a critical mass of sociopaths ⊕ What should be the collective term for a group of sociopaths? You know, like “a conspiracy of ravens” or “a murmuration of starlings”. Once comes to mind immediately but I will leave figuring out which as an exercise for the reader. the minority rule kicks in. Soon enough, everyone must exhibit sociopath-like behavior just to stay in the game. Like Venkatesh Rao recently wrote: “I’m a good person, but everyone is out to get me, so I’d better try to get them first. I’m still a good person.”

Those who don’t adapt, retreat. Sometimes, if we are lucky, they even write about it. And there we have a paradox, in that the same technology supercharging sociopaths in their quest for bullshittification is enabling more and more people to retreat to a life of quiet content. For now.

• Matt Novak on Bluesky: “Let’s talk about tonight…”. Behold the banality of evil.
• Scott Sumner: The odd disappearance of the business cycle. In which an economist wonders why everyone is so down on the economy when the numbers tell us that we live in financial nirvana. Well I can think of a few reasons thanks to Kyla Scanlon’s newsletter. Her “Everyone is Gambling and No One is Happy” from December 2025 addresses Sumner’s confusion head on.
• Joan Westenberg: Why I quit “The Strive”. Westenberg doesn’t call it that, but she describes the founder trap — a funhouse mirror version of the upper middle class trap. Indeed, her article fits neatly into Wednesday’s congames.
• Adam Ruben for Science: Cite unseen: when AI hallucinates scientific articles. The preeminent scientific journal discovers hallucinations. The moral is that those who ask Kenneth the page to write their dissertation deserve everything they get.
• Bonus: Little Snitch for Linux. An OG MacOS app now has a proper Linux version. May it be a sign of things to come.

“A whole civilisation will be destroyed - what an appalling way for a president to talk. Future generations - if we survive will look back and ask how this president could have remained in office. Either Article 25 or impeachment must be exercised.” (👍 339, 👎 117)

“Textbook definition of a terrorist: If I can’t have my way, then I will blow up stuff.” (👍 330, 👎 99)

“Independent Christian and I am actually ashamed of my vote for Trump at this point. His post are vile, childish and disgraceful at every level. He is a tarnish on our nation. He WILL NEVER BE A Reagan…..” (👍 117, 👎 22)

“That is such a sick thing to say. I voted for him 3x, but making a threat like that is no better than the threats Iran has made. Stooping down to their level is a huge turn off. I’m sick of hearing his rants.” (👍 117, 👎 16)

“We use to believe Maga when they said “Make America Great Again” instead of DRAINING the swamp.. they became the swamp. This sick version of America Is not who we are as a Nation, never was, and never should be.” (👍 95, 👎 13, 🇺🇸 6)

The news article with the comments is here. Unlike with previous “happenings” where supporters showed up in great numbers to downvote the opposition, the above is a representative sample of the most highly ranked posts. Scrolling through — and hand to heart the only time I scroll through Fox News comments is at times like this, so about once every few months — my mind flashed back to mid-January 2020 when I checked out N95 masks available on Amazon and saw that they were all either out of stock or selling for $100+ per pack. Motivated reasoning FTW.

Today I learned of the More Perfect Union channel on YouTube and I cannot stop watching. It is like investigative journalism never died and the younger generations somehow carried the flame I thought extinguished under the deluge of talking cable TV heads.

It would have been even more perfect without the clickbaity made-for-YouTube thumbnails and video titles but if that is what it takes to keep it afloat it is a small price to pay.

“The pessimist and the prophet” is the current title of the online version but only if you read the article itself — everywhere else on the website it is the more verbose and I presume SEO-friendly “The Harvard professor who foresaw our age of anger – and what happens next”. Neither is what is used in the print edition, the more poetic “Meditations in an emergency”. Common to all three is that they are nowhere to be found on the FT’s home page, though to be fair it is referenced in the top right corner of the front page in print, above a Mad Men-esque illustration and with an altogether different teaser title: “The limits of liberalism; Philosopher Michael Sandel”.

I have never heard of Sandel before, of his 12-part lecture series about Justice (available on Youtube free of charge) or of his 1996 book Democracy’s Discontent which seems to have predicted the perils of globalization and neoliberalism without having to reference lizard people or secret cabals. ⊕ In this it reminded me of False Dawn which came two years later, though of course I will have to read Sandel’s book first to confirm. In the article, FT commentator Martin Sandbu, who is also a former student of Sandel’s, retells their recent conversations about, well, the current goings on and what happens when you take morals out of politics and rely on “free” markets for guidance:

Sandel’s j’accuse is that this kind of liberalism took what should have been the most political questions out of politics, leaving them to be settled by market mechanisms. I proposed that this was similar to the appeal of “effective altruism”, the neo-utilitarian moral theory popular among students and tech bros, which reduces moral questions to basic calculations of effectiveness. “Exactly,” he said.

In an updated edition of Democracy’s Discontent, Sandel gives the example of Barack Obama’s approach to the 2008 financial crisis. “By standing between the bankers and ‘the pitchforks’,” as the public demanded legal limits on bonuses and no bailouts for banks, “Obama sought to mollify the public outrage, rather than give it voice. [He] treated the financial crisis as a technical problem for experts to solve, not a civic question about the role of finance in democratic life.”

On America’s fake meritocracy:

One derivation of market-friendly liberalism Sandel has long questioned is meritocracy, the idea that society should be organised to give the most able the advancement they deserve. I remember how he would warn us teaching fellows that in the classes debating distributive justice, undergraduates would all preach meritocracy. They were adamant they had earned their Harvard places through hard work alone. In the lecture hall, Sandel would then ask the 800 or so assembled undergraduates to raise their hand if they were their parents’ first (or only) child. He still does this today, and when he does, “75 to 80 per cent of the students raise their hands and there’s an audible gasp when they look around and notice that”. The over-representation (more than half of US children are second born or later), combined with plausible reasons why birth order matters for parental attention and other advantages, is a powerful prompt for Sandel’s students to rethink whether they can really claim meritocratic achievement.

On the class divide: ⊕ But of course as more and more people attain the right to the skybox, those who do not want to mix with the rif-raf build skybox on top of skybox on top of skybox to form an ever-growing hedonistic mountain.

Then there was what Sandel calls “the skyboxification of public life”, a reference to corporate boxes in sports stadiums. Sports events were once a class-mixing experience. Ticket price differences were modest. “Everyone had to stand in the same long queues to use the bathroom, everybody had to drink the same stale beer and eat the same hot dogs. When it rained, everyone got wet. But with the advent of luxury skyboxes, that no longer was the case.” It’s a specific example of what he calls one of the most corrosive effects of growing inequality: that winners and losers increasingly “live separate lives”. This is not just a matter of distributive justice, of unequal incomes, but that we lose the “chance encounters” [that] remind us of our common citizenship, “of what it is we share”. How many of us at the winning end of these developments have given much thought to what we have collectively lost in the process?

Unlike the cadre of neoliberali journalists across the pond — e.g., the editorial board of The Atlantic — Sandbu owes up to his generation’s failure to make the world better and can at least contemplate the possibility that our current predicament is the direct consequence of their hubris. And surprisingly considering FT’s target audience, the comments to the article are uniformly positive. There may be hope yet.

In other news, Tyler Cowen has jumped so high over the shark that he is now levitating somewhere in Earth’s orbit, therefore achieving the correct position for a neutral observer of current events. Even the comments to his post were (somewhat surprisingly, but correctly) unkind.

So says this NYT headline (gift link). In reality, and in the article itself:

The tool might also be more useful for trainee doctors than for experienced specialists, said Dr. Diane Simeone, a pancreatic surgeon at the University of California San Diego. Some of the tumors that the tool caught in the Nature Medicine study should have been “super obvious” to well-trained radiologists even without A.I., she said.

But she acknowledged that it could be a valuable backstop for hospitals where specialists are in short supply.

This is based on the data So yes, A.I. is finding deadly tumors that an overworked and/or undertrained doctor might miss. Which is valuable, but a different message altogether from the one that the headline was trying to convey.

Separately, is “in China” becoming the new “in mice”? ⊕ The link is to a PLOS One blog from 2021. The most recent post there as of the time of my writing this is a scathing and rather unfair review of the science of Pluribus. I refrained from adding it to my feed reader. What assumptions do writers have, and what emotions do they raise in readers, when they report about things happening “in China”? Was it the same with the Soviet Union? Whenever someone fans the flames of mimetic rivalry, I grab my wallet.

With today’s Alphaville, I have never been more proud of paying for a (not cheap!) subscription. (ᔥJohn Gruber, who also provided some non-gift-link-requiring context)