Here is an obvious analogy for you: the physical world — meatspace, if you will — as “meat” of an actual body, both skeletal (muscles, ligaments, tendons and such), and visceral (entrails, the liver, vital organs); the internet as nerve impulses connecting the various parts both sensorially (how are the navels of the world doing these days?) and in effect (from Facebook groups to GoFundMe pages bringing actual change).

You know how X and other social networks made everything feel connected to everything else? Well, there is an organic counterpart to this phenomenon, and it’s called a generalized tonic-clonic — or grand mal — seizure, manifesting, in the clonic phase, in widespread convulsions of the body.

The reason why our bodies are usually not convulsing is that the nerve impulse pathways are tightly controlled in space: there are separate nerves, differentiated brain areas for different roles, and let’s not forget the biggest separation of them all: two semi-independent brain hemispheres connected only by the corpus callosum which, imagine this, is sometimes cut completely for treatment of refractory seizures. There is also chemical separation: many of the pathways are inhibitory, and the most abundant neurotransmitter in the body is not dopamine, serotonin, acetylcholine or others you’ve heard of because they go haywire, but glycin, a modest amino acid which people don’t hear about because it is so good at its job of tamping down bad impulses.

The world’s ongoing convulsions started — after an initial tonic phase — right after we have all become interconnected: Hezbollah, Hamas, and your neighborhood association all hooked up to the same firehose. There is a feeling at the edge of my consciousness that the answer to solving them is in ourselves, and not in a new age self-fulfilment way but in pragmatic steps we can take to extrapolate from this most obvious analogy.

My friend and fellow oncologist Timothée Olivier has just started a YouTube channel called Primum Non Nocere — yay for Latin — and the first video, about reading clinical papers, is well worth 40 minutes of your time.

The recent conversation between Peter Attia and Russ Roberts on cancer screening and longevity has left a good impression, so in case you rushed out to buy his new book, Outlive, here is some thoughtful criticism. Biennial colonoscopies and whole-body MRIs at any frequency are indeed unreasonable.

The first one is tomorrow, and it’s a good one!

• The Ethics of Using Large Language Models by Nick Asendorf, PhD. Wednesday, October 4, 2023 at 12pm EDT.
• Clinical Center Grand Rounds: Pericles and the Plague of Athens by Philip A. Mackowiak, MD, MBA. Wednesday, October 11, 2023 at 12pm EDT.
• Understanding and Addressing Housing Instability for Cancer Survivors by Angela E. Usher, PhD, LCSW, OSW-C and Brenda Adjei, MPA, EdD (and no, I don’t know what most of those acronyms mean). Tuesday, October 17, 2023 at 2pm EDT.
• WALS lecture: The Lives of Bacteria Inside Insects by Nancy A. Mora, PhD. Wednesday, October 25, 2023 at 2pm EDT.
• Reading Remedy Books: Manuscripts and the Making of a National Medical Tradition by Melissa B. Reynolds, PhD. Thursday, November 2, 2023 at 2pm EDT. And yes, I know it’s in November, but I likely would have missed it for the next post since it is so early in the month.

The 2023 Nobel Prize in Medicine went to Katalin Karikó and Drew Weissman, and deservedly so. I do not look forward to the re-writing of history that will inevitably come about the role that the NIH, University of Pennsylvania, and academia in general had in their work. As a reminder:

“Every night I was working: grant, grant, grant,” Karikó remembered, referring to her efforts to obtain funding. “And it came back always no, no, no.”

By 1995, after six years on the faculty at the University of Pennsylvania, Karikó got demoted. She had been on the path to full professorship, but with no money coming in to support her work on mRNA, her bosses saw no point in pressing on.

She was back to the lower rungs of the scientific academy.

“Usually, at that point, people just say goodbye and leave because it’s so horrible,” Karikó said.

She didn’t quit. But even when the breakthrough came, the leading journal saw it as “incremental”:

“The breakthrough, as you put it, we first sent to a Nature journal, and within 24 h, they rejected it as an incremental contribution. I started learning English only at university, so I had to look up the meaning of the word incremental! Anyway, we then sent it to Immunity, and they accepted it (3). We literally did all the work ourselves, Drew and I. Even at the age of 58, I didn’t have much help or funding to perform the experiments, so I did them with my own hands. It took us a while to publish the follow-up paper in Molecular Therapy in 2008, where we presented data on the superior translation of the pseudouridine-containing mRNA and the lack of immune activation in mice.”

The story gets more tangled from there: Karikó and Weissman co-founded a company that failed, then joined BioNTech, and in parallel Moderna started working on their own modified RNA platform, and none of it would have mattered an iota if SARS-CoV-2 hadn’t provided the unfortunate opportunity for mRNA vaccines to shine. For all of our (deserved!) ex post glorification of everyone involved, no Covid-19 — no glory.

Which reminds me very much of The Tartare Steppe’s lonely soldier Drogo who wastes away his life guarding a fortress from the barbarian hordes that don’t arrive until it is too late for him to shine in battle. How lucky for us all that humanity has enough Drogos, and how lucky for this particular pair of soldiers that their Tartars showed up on time.

Emily Fridenmaker, who is a pulmonary disease and critical care physician, writes on X:

Everything is so complex.

Logging into things is complex, placing orders is complex, figuring out who to page is complex, getting notes sent to other doctors is complex, insurance is complex, etc etc. But we just keep doing it.

At what point is all this just too much to ask?

There are a few more posts in that thread, and I encourage you to read all of it to get a sampling of why doctors feel burnt out. Whether you are in medicine, science, or education, your professional interactions have slowly — They Live-style — been replaced by a series of fragile Rube Goldberg machines that worked great in the minds of their technocratic developers, but break, stutter, stammer, and grind to a halt as soon as they encounter another one of their brethren. Which is all the time!

Too much of our professional lives has been spent playing around with a series of Rube Goldberg nesting dolls, ⊕ Before reading I Am a Strange Loop I would have apologized for mixing metaphors, but this is how our brains think and it doesn’t have to make sense in the physical world to be useful, so apology rescinded. 2FA inside a 2FA, and if Apple is wondering why people are taking more and more time to replace their aging iPhones, I bet a good chunk of them dread doing it because they don’t even know how many different authenticating services, email clients, education portals, virtual machines — and all other needless detritus sold to management by professional salespeople — they would need to log back into.

Don’t get me wrong: Rube Goldberg machines are fun to play with — The Incredible Machine was one of my first gaming memories — and they can even be useful for individual workflows. But mandating that others use your string-and-pulley concoction that will break at first unexpected interaction is sadistic. Just this Monday we had yet another AV failure at a weekly lecture held at a high-tech newly-opened campus. I knew there would be trouble the moment I saw that the only way to interact with any AV equipment was via a touchscreen that had no physical buttons and no way to remove the power cord, which was welded to the screen on one end, and went into a closed cabinet on the other. Lo and behold the trouble came not two weeks later: we couldn’t get past the screensaver logo. We ended up asking students to look at their own screens while guest lecturers were speaking — and nowadays everyone carries at least two screens with them to school — which was too bad, because I was looking forward to using the whiteboard which is as far from Rube Goldberg as it gets.

Me from 20 years ago would have salivated for that much technology in my everyday life, but I’m hoping it was a function of the time, not of my age, and that kids-these-days know better. My own kids' experience with the great remote un-learning of 2020–2021 makes me hopeful that they will be more cautious about introducing technological complexity into their lives.

There was a major update today in the Maintenance of Certification saga: the president of ASH (American Society of Hematology, which, oh what a coincidence, I mentioned just yesterday) wrote an open letter to the CEO of ABIM requesting to end MOC as we know it. In what is I am sure a completely unrelated announcement, the CEO of ABIM said he would step down in September 2024. He may want to reconsider that timeline.

I don’t hide my disdain for Eric Topol, and of course one has to wonder whether professional jealousy plays a role; he is, after all, a high-profile doctor with thoughts about technology. But this morning I found an excellent counterfactual in Peter Attia who is slightly closer to me in age, moves in high-profile circles, and spends time “creating content” about what I think is a bit of a time-waster for rich people: prolonging lifespan healthspan. In other words, he carries the perfect confluence of properties to create even more disdain on my part; and yet, I think that overall he is an upstanding guy who is smart, no-nonsense, and great at communicating complex ideas.

This was a long-winded intro to my recommendation for today’s episode of EconTalk, which has confirmed my priors and reminded me that it’s never too early in the week to call Topol a hack. Him and Attia are so similar on paper, so different in reality.

While assembling slides for the UMBC clinical trials course I’m helping with, I was reminded that Richard Doll and A. Bradford Hill never received the Nobel Prize for medicine despite conclusively showing by the way of a new-fangled method called a prospective cohort study — it was the late 1950s — that tobacco kills. They both did the work in their early middle age and lived into their 90s, so it’s not like they didn’t make it to see their work validated (like, say, Oppenheimer not being there for the confirmation of his black hole theory). Of course, the committee is not infallible — they did hand out the prize to a lobotomist — but the errors of omission are so much worse.

My same slide deck also mentions Barry Marshall and Robin Warren who (deservedly!) won the medical Nobel for another disease pathogenesis discovery: they showed that the helicobacter pylori bacterium — and not stressful living, bad thoughts, lack of dietary milk and butter, or whatnot — is responsible for gastritis. Marshall conclusively proved this by ingesting the bacteria himself back in 1985; the Nobel Committee was impressed enough by this feat of IRB avoidance to hand him and Warren the prize — in 2005, the year of Dr. Doll’s death!

He died in July and the prize was announced in October so I shall refrain from making any inferrences about the cause of death.

Patrick McKenzie on X:

I hate to sound intellectually vacuous but choose to get more done. At the relevant margins, get more done. Life : culture / peers will routinely tell you it is OK to get less done and you should politely insist on getting more done. The amount of doneness you get is not fixed.

I have been thinking along these lines ever since reading, some dozen years ago, an article about a particularly successful cystic fibrosis center, whose outcomes were an order of magnitude better than average. This was before any new drugs or promising trials were available, and the only reason why they were so much better was that they did more of everything: more frequent follow-up, more intensive manual therapy, more changes to treatment regimen with subtle changes in condition, less complacency.

Nowhere is this more evident than on the inpatient service. It is incredibly easy to coast with reflexive and defensive medicine, putting out small fires like hospital-acquired infections or patient falls, passing on the buck to the next team, shrugging your shoulders about that 60-year-old with questionable CHF (or is it COPD/asthma) exacerbation who is not following the script and doesn’t seem to be getting any better despite being treated for everything. Patients hang around a bit longer, suffer a bit more iatrogenesis, die a bit sooner, not enough for it to be obvious in any particular case but just enough for the outcomes to be worse in aggregate.

Make no mistake: this is how many (most?) American hospitals operate, for the simple reason that there simply aren’t enough doctors and nurses around for the level of attention sick patients with many active complex disorders deserve. But doing more is the American ethos (see the X-post above); not being able to provide more focused care, we dig into the seemingly infinite supply of more drugs, more procedures, more iatrogenesis to which to expose patients, making their condition all the more complex.

Outside of medicine, this is also the difference you can see in “good” and “bad” (for collaboration) institutions: good ones throw water at embers before they become a fire, communicate more frequently and openly, do not leave documents for review “for after the long weekend”. They do more; or rather, each individual there does more and does not pass on the buck to forces unknown which are beyond their control (and the bigger the institution is, the more numerous and more complacent those forces are; incredible how that works). The not-so-good institutions also do more: of emailing, usually, to tell you that something can’t be done.

So yes, choose to get more done, and also make sure you are doing more of the right thing.