Posts in: science

Friday links, with questions and lists

Have a great weekend!


Wednesday links, science and medical


Tuesday links bonanza

Your life’s goal should be to become the most improbable person you can be. Your path, your character, your life, should be the most unlikely, the most unexpected, the least predictable version you can make. Improbable lives have fewer competitors, more unique rewards, and are harder to replace with AIs, since AIs run on the predictable. This is true whether you favor traditional humanist directions or work on a frontier.

This is a nice preamble to a bit of personal news I can finally share: I will soon be going back [Note: It is a qualified “back”, as I have never actually practiced medicine full time, being either in training, doing clinical research as my main job, or being out of clinic altogether save for a few hours a week doing charity work. ] to the practice of clinical medicine. This week is in fact the last in my current position, which had been a magnificent experience but was going, as the careful reader of this blog would have already noted, in a direction not entirely suited to my preferred lifestyle and more importantly — let’s not sugarcoat it — values and beliefs. Onwards and upwards!

Whittaker, who is the president of the Signal Foundation (as in the app), had this to say about venture capital back in 2023:

Venture capital looks at valuations and growth, not necessarily at profit or revenue. So you don’t actually have to invest in technology that works, or that even makes a profit, you simply have to have a narrative that is compelling enough to float those valuations. So you see this repetitive and exhausting hype cycle as a feature in this industry. A couple of years ago, you would have been asking me about the metaverse, then last year, you would have asked me about Web3 and crypto, and for each of these inflection points there’s an Andreessen Horowitz manifesto.

It’s not simply that one piece of technology is overhyped, it’s that hype is a necessary ingredient of the current business ecosystem of the tech industry. We should examine how often the financial incentive for hype is rewarded without any real social returns, without any meaningful progress in technology, without these tools and services and worlds ever actually manifesting. That’s key to understanding the growing chasm between the narrative of techno-optimists and the reality of our tech-encumbered world.

Emphasis is mine, as it could be transposed word-for-word into the current world of drug development. Consider it a more polite rewording of prof. Taleb’s take.

Commodified knowledge is “general knowledge” in the sense tested by trivia/quiz contests. In grade school, we actually had a subject on the curriculum called “GK” and kids good at it (I was one of them) got put on quiz teams to represent their class or school. General intelligence of the sort we actually have today is simply AIs trained on general (ie commodified) knowledge.

But the theological motte-and-bailey move that conflates it with some totalizing-universal divine-omniscience idea of “Artificial General Intelligence” traps a great many of even the smartest people. A category error motivated by theological yearnings, validated by second-order Labatutian psychoses, sustained by epistemic bubbles, and encouraged by sketchy business roadmaps that need a story to justify trillion-dollar investments.

This is a charitable way of justifying the AI billionaire panhandlers’ selling of large language models as AGI, even putting the term in official titles. Less charitably, they all know what Yann LeCun has been saying for years: LLMs will never reach human level of intelligence (“ChatGPT, make me a sandwich”). Whether LeCun’s own pursuits are wise is a different matter.

Separately, Rao gives some good book tips and Benjamin Labatut’s When We Cease to Understand the World is now on the Pile.

No quotes because, true to form, everything salient is already in the title. Natural continuation of the debate started last week (see the last link), although apparently written before the new arXiv policy for a 1-year ban for hallucinated references.

Healy wrote a book about data visualization so I feel somewhat foolish in writing this, but I do not find Apple Sports’ presentation least bit confusing: the numbers are absolute, the bars show percentage of the total. If the goal is to have more of each (assists, rebounds, steals, etc.) the bigger bar shows the opposing team’s dominance. It’s fine. Healy’s proposed solutions are all notably uglier and demote low-occurrence events like blocks and steals even though they may be crucial in a game. Shows how little both Healy and Gruber — on whose post Healy riffs — know about the game of basketball.

At Compleat Kidz, a fast-growing chain of autism clinics based in North Carolina, the policy is firm: Naps cannot be longer than seven minutes before children are awakened to resume therapy. The company says this is necessary to prevent fraud since clinics can be paid only when children are awake and getting services. But it also allows the clinic to bill insurers or Medicaid for more hours.

Yes, you have read that correctly. Waking up a child after a 7-minute nap to perform “therapy” — as if anything meaningful can be accomplished in that hypnagogic state — is both cruel and unusual. But not a punishment! It is merely a way to avoid fraud while optimizing revenue under the watchful eye of private equity:

Private equity firms have acquired at least 500 clinics over the past decade. “There’s just huge opportunities to grow these businesses and help increase access to care,” said Jon Krieger, a managing partner at Calex, a financial firm that assists with autism clinic mergers and acquisitions. He estimates the market could grow to $90 billion.

Mr. Market is a bad doctor, an even worse vet and, it seems, a most diabolical nanny.


Tuesday links, academic deep dives

A marvelous overview of various pitfalls in thinking which I will have to read again and with great care to fully understand. As is often the case, the concluding paragraph gives one a good idea of the flavor of the whole text:

At the least, the difficulties of understanding should make all scientists both skeptical and humble, knowing that ‘truth’ is an ever receding goal. We must realize the full range of possible illusions and appreciate that they occur in all approaches. We can reduce false insights and achieve better understanding by embracing diverse theoretical perspectives, research methods, and modes of analysis. This requires constant intellectual humility towards our own theories, models and methods. This recommendation unfortunately competes with forces in scientific societies that foster overstated claims and conclusions: Faced with millions of publications each year, scientists must fight for attention, readers and citations in the research marketplace, and journal editors must seek impact factors, submissions, and readers. In addition, scientists’ beliefs in overstated claims are subject to biases that occur more broadly. Thus, scientists can exhibit trust that increases beyond what is justified for mentors, friends, colleagues, same institutions and affiliations, famous scientists at leading universities and research centers, and decreases for women and minority authors. Do scientists realize the extent to which such factors operate and are they adapting to their existence?

The subtitle is “How GLP-1 Development Was Abandoned in 1990”, and it attests to a 30-year delay in bringing these revolutionary drugs to patients, because someone at Pfizer thought they understood what was going on. So the pipeline is even more broken than I thought.

A series of well-referenced historical vignettes whose purpose is to bring tech-adjacent people closer to worldviews other than “the toxic strain of neoliberal capitalism favored by venture capitalists and their gushing fans in the tech media.” But you don’t need to know any of that to enjoy his notes on selfishness, corporate psychopathy or people being human in a crisis, to pick a few recent ones.


Wednesday links, with many uncertainties

Oh but we do, at least superficially: “of 130,000 men who became new fathers between 2017 and 2022, almost 800 died during that same 5-year period, and 60 percent of those deaths were from potentially preventable causes like homicide, accidental injury, and suicide” which is about what you would expect for a group of men that skews younger. The authors of the paper make a comparison between fathers who died and those that survived but a more interesting one would have been a demographically matched of childless men. Alas, all we have is all the men in Georgia and lo, for each age range the new fathers have a lower mortality and the discussion appropriately leads with “Fatherhood appeared to be associated with reduced mortality.“ [Note: Another reason to have more children. Though, if you are going to do it solely because of a misguided belief that you yourself would live longer, then perhaps don’t? ] Methinks French — or her headline writer — were fooled by randomness.

Vepdegestrant for breast cancer seems to be another entry in the annals of approved drugs being considered failures by Mr. Market. Let it be noted that a chemist (Lowe) writing for a prestigious peer-reviewed journal (Science) dunks on a drug while citing millions and billions of dollars exchanged or promised to various stakeholders while barely mentioning, and wrongly at that, the actual trial results. “It did not really demonstrate any advantage versus the comparison in the trial, fulvestrant” is factually incorrect: median progression free survival was 5 versus 2.1 months, which, fine, is tiny and may have been the result of statistical shenanigans; but it may also be a true and meaningful incremental improvement and if we are going to dismiss it out of hand then what are we even doing here? The rot runs deep.

It is a genuine mystery of why a mostly agrarian functional democracy with no separatist movements, demographic catastrophes, curses of resource wealth and the other usual suspects of stalled growth should completely flatline their GDP. Mousa shows compelling data and many hypotheses, though I wonder whether there is something that isn’t and can’t be measured which is keeping the country where it is. And if you are thinking that oh, GDP can’t measure happiness, I bet that at least they are happy, think again: it was the 4th least happy country last year. But then the “Happiness Report” methodology takes GDP into account (!?) so it is almost impossible for a GDP-poor country to break through in the rankings.

This is about slides shared via email, never meant to be presented, but rather serving as a landscape-oriented picture book for adults. I don’t know what is behind communication-by-slide, and as a seminar-attending Tufte acolyte I abhor it. Management consultants spreading them around like a viral respiratory disease — which is the thesis of the blog post — certainly has something to do with it, but the syndrome is now bottom-up as well. My third-grader asked me just this morning why they were forced to watch and make (!?) slides at school.


Medical links, Good, Bad and Ugly

The good: How an ‘Impossible’ Idea Led to a Pancreatic Cancer Breakthrough by Gina Kolata and Rebecca Robbins for The New York Times. The breakthrough discussed is the real deal, and they manage to do it in a measured tone which correctly identifies daraxonrasib as a stepping stone and not a miracle cure. It has this important note up top and not buried down at the end:

The pills, three taken daily, are not a cure — eventually, daraxonrasib stops working. Many patients do not respond. And it has side effects that can be harsh, including rash, diarrhea, fatigue, nausea and raw, split fingertips.

How refreshing — I hope Derek Thompson takes note.

The bad: The Human Body’s Hidden Pathways by Dr. Avraham Z. Cooper, who is a pulmonary/critical care physician at the Ohio State University, for The New York Times Magazine. For the life of me I can not figure out the point of this post-modern journalistic exercise.

Nominally it is about a peer-reviewed research article which came out in 2021 under the title “Evidence for continuity of interstitial spaces across tissue and organ boundaries in humans”. The NYT Magazine staff did not deem it worthy of being linked to, but here it is in its entirety. In it, the authors showed small fragments of tattoo pigment migrating into tissues — skin and colon — deeper than they expected. We are not talking about ink being injected into a bicep and showing up in someone’s rectum here, but rather a series of biopsies of tattooed skin or the lining of the colon where there is a lot of pigment up top, and much less and in smaller pieces down at the bottom of the slide, deeper in the tissue.

Let me pull out my rarely used master’s degree in histology and note that this is hardly surprising. Connections between cells are not exactly air-tight — other than maybe in the brain and the testes — so of course there is some gel-like fluid circulating in the space. Or did the original article’s authors not realize why people tend to rub their feet when they get swollen?

But that is only the introduction. The meat of the article is Dr. Cooper’s theoretizing that this has something to do with — drumroll, please — acupuncture. With no evidence, mind you, but a tingling sensation in the back of his neck or somesuch. By the time the 30th single-sentence screen scrolls by we are firmly in bullshit territory, in the formal sense of the word. Caveat lector.

The ugly: Longevity Medicine - An evidence based guide by Dr. Vinay Prasad who is out of the FDA and back making YouTube videos. And oh my, the contrast between the most recent thumbnail and the one posted just before he joined the FDA is striking. Has it only been a year? No wonder that his first topic back as an influencer is about longevity.

A sidenote here which I will put at the end: the increased interest of Silicon Valley types with longevity, and I am not thinking only about Bryan Johnson’s delusions here, reminds me of the recently quoted speech Charlie Chaplin gave at the end of The Great Dictator, the relevant quote being that “so long as men die, liberty will never perish.” Good for us that snake oil salesmen are still the longevity field’s most prevalent phenotype.


This week in hubris

What possessed me to type x.com into the address bar I can tell you not, but there I was, staring for the first time in weeks at the “For you” tab. And there it was, in all capital letters: “THIS IS HOW WE CURE PANCREATIC CANCER”, staring back.

That was the X-crement of one Derek Thompson, writer for The Atlantic, podcaster, abundance enthusiast. It was promoting his most recent blog post which, being on Substack rather than X, had a more subdued name: “How AI Could Help Cure Pancreatic Cancer”. It is, supposedly, an interview with a co-author of a paper with an ever-less-so boastful name: “Next-generation AI for visually occult pancreatic cancer detection in a low-prevalence setting with longitudinal stability and multi-institutional generalisability”. Most of the interview, however, is behind a paywall which I shall not climb.

Above the fold is Thompson’s exuberant, hyperoptimistic speculation. He approaches the problem from the perspective of the three recent developments — one from above, the other two previously discussed — but presents the areas which they are “solving”, targeting KRAS mutations, pancreatic cancer’s immune evasiveness, difficulties with early detection, as the sole reasons why the disease is so difficult to treat.

But that is disingenuous. There are so many more reasons why it is hard: the uniquely hostile, acidic, high-pressure environment of the tumor that makes drug delivery to it nigh-impossible. It’s propensity to metastasize — spread to distant organs — no matter what size the original tumor is. A biochemical storm it stirs up in the body leading to rapid weight loss, blood clots and horrendous pain which are distinct even among other cancers. Why not highlight those three as the “3 broad reasons why pancreatic cancer is so hard to treat”, to use Thompson’s terminology? Well, no recent high-profile studies for those, are there?

I understand that he has some personal reasons to be interested in pancreatic cancer, and I am sure it is coming from the best of intentions, but please.


Friday link potpourri

To those who can hear me, I say - do not despair. The misery that is now upon us is but the passing of greed - the bitterness of men who fear the way of human progress. The hate of men will pass, and dictators die, and the power they took from the people will return to the people. And so long as men die, liberty will never perish…

Soldiers! don’t give yourselves to brutes - men who despise you - enslave you - who regiment your lives - tell you what to do - what to think and what to feel! Who drill you - diet you - treat you like cattle, use you as cannon fodder. Don’t give yourselves to these unnatural men - machine men with machine minds and machine hearts! You are not machines! You are not cattle! You are men! You have the love of humanity in your hearts! You don’t hate! Only the unloved hate - the unloved and the unnatural! Soldiers! Don’t fight for slavery! Fight for liberty!

Amen.


Thursday links, Nautilus science edition


Friday links, science-y