📚 Finished reading: Moonbound by Robin Sloan, which is a light, fluffy, summer-time — someone less charitable may have said paper-thin — version of some of my favorite sci-fi series. But please don’t mind my inner snob showing off: it is a fine book and I anxiously await the sequel.

My boss at the NIH was in his late 80s when I started working there, early 90s when I left. There was an obvious physical decline into complete frailty during those four years, but he was as sharp, lucid and stubborn as ever. You don’t get to work into your 90s unless you have it your way, and “the way” became shorter hours in the office with prolonged nap time, sometimes during meetings, while maintaining the final word on anything that happens in the lab.

So, “the mind is willing but the flesh is weak” often came to mind, and until we develop a Futurama-style brain-in-a-box there are limits that biology imposes which can’t be overcome through force of will. You hate to see it, but we will be seeing it more and more often as the Baby Boom generation gets into its sunset years. Not because they’re any more selfish than other generations, mind you (my old boss was of the Silent generation), but rather because they are the most numerous and the biggest beneficiaries of death-delaying medical advancements.

It seems to me that the higher up the person is in the hierarchy and the longer they have worked in the field (my boss spent 60 years at the NIH), the harder it is to imagine anything other than staying on the job until an act of God intervenes. This is exactly what happened; I was gone before then, but there were many in the lab who were left scrambling for a new position, taken by complete surprise that their 90-plus-year-old chief was no longer with us.

So it goes…

If you are an American, the country’s best decade was whenever you were a teenager, says The Washington Post. Compare and contrast to Serbia, whose best decade is more dependent on your politics and can be anything from the 1340s to the 1960s. My teenage years were, of course, not so glorious.

Why haven’t biologists cured cancer? asks Ruxandra Teslo in my new-favorite Substack newsletter, and answers with a lengthy analysis of biology, medicine and mathematics. Clinical trial costs inevitably come up, and I know it is a minor point in an otherwise well-reasoned argument but this paragraph stood out as wrong:

Clinical trials, the main avenue through which we can get results on whether drugs work in humans, are getting more expensive. The culprits are so numerous and so scattered across the medical world, that it’s hard to nominate just one: everything from HIPAA rules to Institutional Review Boards (IRBs) contribute to making the clinical trial machine a long and arduous slog.

What happened here is the classical question substitution, switching out a hard question (Why are clinical trials getting more and more expensive?) with an easy one (What is the most annoying issue with clinical trials?). Yes, trials involve red tape, but IRB costs pale in comparison to other payments. Ditto for costs of privacy protection.

If we are picking out likely reasons, I would single out domain-specific inflation fueled by easy zero-interest money flowing from whichever financial direction into the biotech and pharmaceutical industries, leading to many well-coined sponsors competing for a limited — and shrinking! — pool of qualified sites and investigators. It is a pure supply-and-demand mechanic at heart which is, yes, made worse by a high regulatory burden, but that burden does not directly lead to more expensive trials.

There are some indirect effects of too much regulation, and at the very least it may have contributed to more investigators quitting their jobs and decreasing supply. They also contributed to regulatory capture: part of the reason why industry has been overtaking academia for the better part of this century is that it’s better at dealing with dealing with bureaucracy. But again, these costs pale in comparison to direct clinical trial costs.

Another nit I could pick is the author’s very limited view of epigenetics: if more people read C.H. Waddington maybe we could find a better mathematical model to interrogate gene regulatory networks, which are a much more important part of the epigenetic landscape than the reductionists' methylation and the like. But I’d better stop before I get too esoteric.

Breaking my “no politics until November” promise to self in order to quote today’s Stratechery update:

[The] Democrats gave up the enviable position of being the default choice for people who didn’t want to think about politics at all.

And this is exactly what has been bothering me since 2016. I spent my whole childhood and young adulthood in a country (Serbia) where you had no choice but to think about politics, and a big part of coming to the US was not having to think about it too hard. Alas, instead of the Balkans becoming westernized the West has been balkanized.

If there had been a webpage monitoring the progress of the actual moonshot in the 1960s, it would have said stuff like “we built a rocket” and “we figured out how to get the landing module back to the ship.” In 1969, it would have just said, “hello, we landed on the moon.” It would not have said, “we are working to establish the evidence base on multilevel interventions to increase the rates of moon landings.”

This is Adam Mastroianni skewering the “science moonshot” initiatives, and rightfully so. If all we have to show for them are 2,000 papers full of mealy-mouthed prose, it was a ground shot at best.

📚 Finished reading: The Will to Battle by Ada Palmer, who continues to mix enlightenment philosophy, history and some dark, dark humor to produce an artifact from the 25th century that may answer some question we have in the 21st. I am at once sad and relieved that there is only one book left in the series.

Things You Can’t Invent:

There are inherent utopian assumptions about our ability to create a better world. The arrogance of those assumptions consistently produces a world of unforeseen consequences.

This comes from an Orthodox priest, but may as well have been written by Nassim Taleb. Effective Altruists and those adjacent should take note.