A working catalogue of twelve open problems in biology — each a concrete, testable target for the field.

164 points•artninja1988•11 days ago•121 comments•

121 comments

doctoboggan10 days ago
Someone should make the millennium problems for AI alignment so the frontier labs will actually try to solve that problem.
aleph_minus_one10 days ago
> Someone should make the millennium problems for AI alignment so the frontier labs will actually try to solve that problem.

Rather: Someone should make the millennium problems for human alignment so the top researchers will actually try to solve that problem. :-)

a83ndoija9isjd10 days ago
They are already human-aligned. That is the entire issue.
hodgehog1110 days ago
A group already (sort-of) has for the broader theory: https://arxiv.org/abs/2604.21691

It's a good list, but "alignment" is much more targetted. I attended a workshop with researchers from OpenAI and Anthropic also present, where the objective was to hash out what the problems in alignment even are. This, it turned out, was extraordinarily difficult.

The problems with alignment are to do with how we define and search for this vague notion when it is mathematically ill-posed at present.

wise_blood10 days ago
I was gonna write "Implement the three laws of robotics", but then I remembered that the point of the short stories is that there are a number of loopholes...
daveguy10 days ago
You'd think that believing they are going to destroy humanity would motivate them.
an0malous10 days ago
If you ignore what people say and instead observe what they do, the world makes a lot more sense.
throwup23810 days ago
Some ~~people~~ corporations just want to see the world burn.
alansaber10 days ago
They're for-profit corporations above all.
vjvjvjvjghv10 days ago
The only thing the frontier labs are interested in is their trillion dollar IPOs.
pfisherman10 days ago
Biology already has numerous “Millennium Problems” and the rewards are much more than $1M. For example, reverse Alzheimer’s Disease. Or less ambitious develop high fidelity in vitro and animal models of human disease.
phreeza10 days ago
Those don't have the property of being easily verified, which the problems proposed here do. I think that's a smart idea because it's a way to capture quick PR seeking AI-lab dollars for quite useful outcomes.
pfisherman10 days ago
Being easily verifiable does not elevate something to the level of being a grand challenge. It really drives home the point that biology is not math or coding.

I guess to me the grandiosity here feels fake and unearned - like they vibe slopped it together without much input in the way of deep thought or expertise.

For example, synthesize arbitrary dna sequences > 3000 nt in length with error rate < 0.001 at > 95% purity. Easily verifiable, beyond the frontier, and generally useful.

jszymborski10 days ago
I think those are better described as problems of medicine whereas the problems here are indeed about fundamental biology
daoboy11 days ago
This is all well outside my area of expertise, but my impression is that Michael Levin's work with bioelectricity is on the cusp of #6 Somatic limb regeneration.

SMEs please correct the record if I'm mistaken.

jodacola11 days ago
Unfamiliar with Levin’s work, but:

There’s also this study [0] I read recently, along a different path of using known growth factors and proteins to kick off regeneration.

[0] https://www.nature.com/articles/s41467-026-72066-8

gavinray10 days ago
ECM (Extracellular Matrix) has been studied for similar properties:

https://www.biorxiv.org/content/10.64898/2026.08.05.742898v1...

"Extracellular matrix particle treatment induces digit regeneration in soft-tissue preserved amputation (SPA) model of adult mice"

pixl9710 days ago
Everyone interested in biology and intelligence should look up Michaels work, it is amazing because he's ignored a lot of assumptions that are held by the community and come up with new and interesting tests.

Also his work on algorithmic intelligence in cells and the mathematical foundation of intelligence will change many fields, including AI, if it can be empirically tested.

usernametaken2910 days ago
Wait a minute:

> Cryopreservation + Demonstrate the ability to cryopreserve and recover live wild-type mice with high viability. Specifically, demonstrate the reversible cryopreservation of live, intact, wild-type adult mice in a whole-body frozen or vitrified state. The mice must remain frozen or vitrified for at least 24 hours, must be recovered with >99% viability, and must not suffer any permanent organ damage or bodily harm. Somatic genetic engineering is discouraged but permitted. All experiments must be conducted with ethics approval.

This has been done in the 50ies, freezing and thawing mice with microwaves. IIRC the recovery rate was about 74% with no observed side effects. The research was given up on because in this specific case a mouse is a bad biological model. Thawing agents must scale cubically with size. The author says that at approximately the size of a cat you can’t quickly enough evaporate all the agent because the energy required will simply burn the tissue.

TLDR: it’s possible, it’s been done, it could be perfected if necessary, it does NOT scale beyond mice

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