Roblog

Over at Astral Codex Ten, Scott Alexander digs into the science behind anti-obesity drug Ozempic, and the subsequent array of secondary effects that have emerged in the scientific literature.

“GLP-1 receptor agonist medications like Ozempic are already FDA-approved to treat diabetes and obesity. But an increasing body of research finds they’re also effective against stroke, heart disease, kidney disease, Parkinson’s, Alzheimer’s, alcoholism, and drug addiction.

“There’s a pattern in fake scammy alternative medicine. People get excited about some new herb. They invent a laundry list of effects: it improves heart health, softens menopause, increases energy, deepens sleep, clears up your skin. This is how you know it’s a fraud. Real medicine works by mimicking natural biochemical signals. Why would you have a signal for ‘have low energy, bad sleep, nasty menopause, poor heart health, and ugly skin’? Why would all the herb’s side effects be other good things? Real medications usually shift a system along a tradeoff curve; if they hit more than one system, the extras usually just produce side effects. If you’re lucky, you can pick out a subset of patients for whom the intended effect is more beneficial than the side effects are bad. That’s how real medicine works.

“But GLP-1 drugs are starting to feel more like the magic herb. Why?”

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Tim Hwang with a great post on long-term scientific experiments:

“If you’re not already familiar… I highly recommend that you immediately stop what you’re doing and visit the Wikipedia page for ‘long-term experiment’. Then, check out Sam Arbesman’s collection of Long Data. Then, Michael Nielsen’s list of long projects.

“If you’re anything like me, the scientific efforts that appear on these lists are deeply compelling. That’s due in part to their relative rarity. It’s hard to find cases of an experiment or a data collection effort that grinds away on the scale of decades, and easy to appreciate the uncommon dedication and focus they represent.

“These efforts are also compelling on an epistemological level. They suggest that there is a wealth of valuable knowledge to be gleaned from even fairly humble explorations that operate over a long, long period of time.”

Tim reckons that such experiments are under-performed, especially given how simple and cheap they can be relative to the insights they can deliver. He suggests a new way of funding them:

“One approach could be to popularize a style of grant that I call TILT – tiny investment, long term. Under a TILT grant, a foundation or government agency would award grantees a relatively small stream of money spread out over an extremely long period of time, say twenty or thirty years.”

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David Greer explains the importance of plankton, those invisible but essential marine creatures:

“Tiny and virtually invisible as most plankton are, they make up more than 90% of the biomass in the world’s oceans and are collectively the lowest rung on the marine food chain. Everything we eat that comes from the ocean ultimately depends on plankton for its existence. As if that’s not reason enough to pay attention to the future of plankton, it’s worth considering that about half of the oxygen we take in with every breath also owes its existence to plankton.”

Like all other life on earth, plankton are threatened by the effects of climate change – with potentially disastrous consequences. #

I was previously familiar with Murry Gell-Mann only through Michael Crichton’s Gell-Mann amnesia:

“Briefly stated, the Gell-Mann Amnesia effect is as follows. You open the newspaper to an article on some subject you know well. In Murray’s case, physics. In mine, show business. You read the article and see the journalist has absolutely no understanding of either the facts or the issues. Often, the article is so wrong it actually presents the story backward – reversing cause and effect. I call these the ‘wet streets cause rain’ stories. Paper’s full of them.

“In any case, you read with exasperation or amusement the multiple errors in a story, and then turn the page to national or international affairs, and read as if the rest of the newspaper was somehow more accurate about Palestine than the baloney you just read. You turn the page, and forget what you know.”

But this interview, from 2003, reveals a thoughtful, interesting, curious and funny man whose first interest was in languages and who retained a humanity and humour throughout his scientific career:

“I was still discouraged, though, about having to go to MIT, which seemed so grubby compared with the Ivy League. I thought of killing myself (at the age of 18) but soon decided that I could always try MIT and then kill myself later if it was that bad, but that I couldn’t commit suicide and then try MIT afterwards. The two operations, suicide and going to MIT, didn’t commute, as we say in math and physics jargon.”

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The news is full of stories lifted straight from scientific papers, lots of which are of dubious quality. David Epstein highlights one recent example – a story with the headline “surgeons who listen to AC/DC are faster and more accurate” – which demonstrates a common abuse of statistics:

“I recommend that when you see this sort of ultra-nuanced effect in a news article, it may be a sign that the researchers inappropriately (but often not maliciously) sliced and diced their data in order to create some tantalizing positive finding, which – given enough data and enough slicing and dicing – they will inevitably find among the many possible false positives.

“Let’s say a study starts out asking whether music makes surgeons perform better, but the results show nothing. Dead boring. So then the researchers separate the data into surgeons who heard soft rock versus hard rock. Ok, now the hard rock shows an effect. But, hmmmm, still no effect for soft rock. But if you look only at the data when the music is low-volume, there’s an effect. Interesting! Headlines!

“But the reality is often that the researchers just sifted the data so much that they were bound to find false positives.”

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A fascinating paper that analyses how humans navigate cities on foot, and how their routes compare to the optimal ones.

It turns out that we’re remarkably good at finding near-optimal routes without resorting to complex calculations; we use heuristics and we “satisfice” for a good-enough route. But it turns out that, when our route planning is sub-optimal, it’s sub-optimal in predictable ways.

One such puzzling way we consistently differ from the optimal route is our tendency to pick asymmetrical routes; we walk a different route on our way to a destination than the one we walk coming back. This reveals a heuristic that we use, which the researchers called the “initial straightest segment” heuristic: we’ll set out on our journey by heading in a direction that’s as close to the direction of our ultimate destination as possible, even if the shortest route actually means taking a slightly different direction first. On the way back, we do the same thing – which often means picking a slightly different route.

A really neat example of using mobile data to discover fundamental aspects of human behaviour (and in a non-creepy way!)

Christian Bongiorno, Yulun Zhou, et. al. “Vector-based pedestrian navigation in cities”. Nature Computational Science 1(678–685), October 2021 #

Holden Karnofsky, founder of the GiveWell project, explains why the question “does X cause Y?” is trickier than you might think. #

A surprisingly engaging – and informative – article on the evolution of the… well, you’ll get the picture.

“One unusually aerated specimen, a type of polyclad flatworm, sports multiple anuses that speckle its backside like feces-spewing freckles. Two others, a pair of sponge parasites called Syllis ramosa and Ramisyllis multicaudata, will twine their body through host tissues like a tapestry of tree roots, with each tip terminating in its own proprietary butthole; they have hundreds, perhaps thousands, in total. (It’s not totally clear why these animals and others spawned an embarrassment of anuses, but in at least some cases, Hejnol thinks it’s a logical outcome of a branched digestive system, which can more easily transport nutrients to a body’s every nook and cranny.)”

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