The Millennium Problems for Biology

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

> The problem would likely be even more impactful if solved in general for small molecule binders, rather than protein binders or antibodies. However, with small molecule binders, synthesis is a major bottleneck that would limit validation, and thus we have chosen to restrict the scope to protein binders.

For small-molecule synthesis, there is https://en.wikipedia.org/wiki/Click_chemistry -- people at my former employer got the Nobel Prize for it. I believe there are companies that let you order such molecules from a set of about a billion, and they synthesize them on-the-fly.

Do we really have to solve these problems though? Why would anyone want to have an inferior bio limb when they can substitute it with a superior and easily repairable/upgradable mechanical limb? Granted that the artificial limbs we have right now are pretty basic, but wouldn’t it make sense to improve it rather than trying to grow new limbs?

Also if you think humans would ever become a space faring species, would it really make sense to stick to our carbon based biology or should we invest in transforming into silicon based beings

Its much harder to produce a good fundamental list of biology problems because we are no where near as far along, so many basic things are not understood. There are still many unknown unknowns and these particular problems are limited to the realm of verifiable in a lab, which rules out much of what makes biology interesting and hard to study, and that is the organisms themselves and the interactions between their cells. The petri dish differs from the rat differs from the human and that is a part of what makes biology harder to progress.

None of these is likely the root to the wide array of chronic illnesses we can't treat and those seem like the next step to really put a lot of research into given how many people suffer from them and where we are today they seem achievable with the right investment.

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.

Not an expert, but as I understand from my colleagues you can make a case for lots of really important problems related to protein folding to be included in the list. As protein folding hasn't been nearly "solved" by alphafold as has been reported in many places.

These are almost all so stupid. Written by people who clearly don't know their chemistry

Reverse translatase and protein amplification in particular.

How the fuck do you plan on selectively priming protein amplification. If you know ANY protein chemistry, you will know "the juice is not worth the squeeze" -- how would I exponentially amplify a protein? I'd do mass spec proteomics, synthesize the DNA, and express it.

Simply amazing that electrofixation is not on the list.

Agreeing on the model gap, the bit left out is that even human-to-human it breaks. Same drug, same dose, wildly different response depending on genotype and gut flora.

> 02 - Cryopreservation

Demonstrate the ability to cryopreserve and recover live wild-type mice with high viability.

> 06 - Somatic limb regeneration

Demonstrate the ability to regenerate lost limbs in adult wild-type mice.

Interesting, but looks like these problems are proposed in September 2026, unlike original 7 Millennium Prize Problems of Maths

So anyone can create a list of problems and slap the name Millennium Problems on them?

Slap an LLM on those and call it a day

Who is this by? Who verifies the result? Is there prize money?

It’s strange they are all engineering problems.

This is a collection of pet projects by folks who are not distinguished biologists. Interesting, maybe, but not to be placed on the same pedestal as the mathematics Millenium Prize of a similar name.

Arguably, the origin of life is a question for all time -- no way that a VC webpage is going to change whether someone takes that problem on, and it will be commercialized with big-name capitalists instead of 'FutureHouse' should it ever be developed in the lab.

It's missing some important stuff? Like creating bacteria that can produce fuels or break down plastics.