Nearly all things don’t matter

Nearly all things don’t matter


How to solve problems 🦢Why I’m solving Aging

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Status: Observation

Look at this:


Now this:


What do you see? Well, one thing you will see is color. There are different cars of different color. And blue and red cells. You also see type: motorcycles and taxis, red blood and immune cells.

My point is simple: we can categorize cars based on color. We can also analyze and hypothesize a lot of interesting things about it. Like, maybe the increase of white cars in the last years is due to climate change?


But this is deeply pointless: none of it explains traffic flows. That can only be explained by

  • maximum speed at which drivers feel comfortable (based on reaction speed + number of other drivers)
  • Where they want to go (based on motivation, incentives, time of day)

None of which are inferable by color.

But most of biology is looking at cells and classifying them by color (flow, antigens) or model (transcriptomics, microscopy). This can work: taxis look different than cars - but we also have Uber, so even if it does you might be missing something. That function follows form is a strong assumption, one I think is mostly wrong. Rather dynamics (goals + incentives) determine function, which can be achieved through many forms (largely because nearly all aspects of form are fungible, given a goal).

Let’s develop tools to make molecular biology more behavioral.

Against Complexity Cope

Related: one of the worst mistakes I see biologists/medics making is looking at this:

And being like “Oh Noo! How could we ever understand this!”

But the truth is: none of what you just saw was actually complex, literally every picture is just a bunch of things wanting to go from A to B, but because occlusion is turned on, they can’t.:


This literally explains EVERYTHING about the picture, because all details (like who goes first) are haggled for between the agents (they have to understand them) and therefore irrelevant (you don’t, as you are just trying to understand what’s going on). Inventing the traffic light:


or the roundabout


become trivial.

I can sympathize with the field: many easy solutions derived from simple models turned out to be wrong or impractical. Beta-amyloid plagues do not cause Alzheimers, because removing them does not heal anyone. But this doesn’t imply that the model is oversimplified, just that it’s wrong. Turns out Alzheimers might just be “Type 3 Diabetes” (too much insulin resistance in the brain), or - even simpler - aged vasculature.

Basically, I suspect that in medicine the “all models are wrong, some are useful” idiom is false, instead “nearly all models are wrong. useless and overcomplicated, but some capture the actually important bits, such that medical problems become engineering challenges”. This leads to the invention of “washing your hands”, variolation, vaccination, surgery (just replace the broken thing), CRISPR for sickle cell, etc. Also simpler models are better: the invention of insulin is great and explained by the early model of “somehow system runs out of insulin, so we just inject it, but its kind of astrology when and how much” to “there needs to be a way to kill overreactive glucose sensors, this fails in some because bad luck, but turning immune system off and on again might fix it” (yes, I predict with >80% confidence that CAR-T cell therapy on B cells will completely solve Type 1 diabetes, see Systems Medicine by Uri Alon for great model of why).

This does NOT make solving aging simple. Figuring out which simple model is accurate is hard - because we (thinking brain) are not cells, or at least lack the tools to really see what cells or tissues are “wanting” (which is way more interesting than what they are, or even what they are doing). See Simple Made Easy for the distinction. But it helps with looking at the system and figuring out which parts can’t matter (like ligaments or bones, which are just support structures for other support structures, so their replacement is easy and without consequence, or the reproductive tract - reproduction is the opposite of aging), which might (kidney, liver, thymus, blood brain barrier and maybe ECM = filters) and which definitely do (brain, mitochondria, vasculature, certain muscles = turn energy into signal).