> 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.
> The petri dish differs from the rat differs from the human and that is a part of what makes biology harder to progress.
They all use DNA.
But I agree that nobody has shown in the lab how any of this leads to a genetic system that can self-reproduce reliably and assemble biomolecules/metabolites. This is a missing link. Just showing how RNA or amino acids arise, says nothing about any genetic system. They can not even answer whether RNA or DNA viruses existed first; and whether these existed before organisms/cells did.
The goal of the suggested "origins of life" goal, as written, isn't to guess at history - it's to create some similar plausible self-emergent system in the lab.
Seems a bit of an ambitious goal for a language model though! There are presumably dozens of steps before you get to an RNA-based full-blown cell, and it's only been very recently that humans have managed to make an artificial self-replicating cell of any type in the lab.
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.
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.
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.
Of course. This is just a list of someone's ideas for equivalently difficult (and transformative) unsolved problems in biology. Many of these would of course have obvious and immediately impactful practical applications, unlike the math problems.
The Millennium Problems list in math was created in 2000, hence the name. There is a $1 million prize for solving any of the problems. Creating this list is just someone's idea of listing problems of equal importance. The name doesn't fit and it's just a list.
In a sense all experimental science has an element of engineering. For instance the first problem, "the origins of life" is framed to require an experiment to show that any proposed mechanism actually works.
Bacteria that break down plastic already exist, both naturally and synthetically. Optimizing those is one of the most popular student projects in my university. Hardly a millennium problem.
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.
I’m going to be honest, I don’t know if improving Rubsico is possible. Nature has had every reason to and billions of years. It’s optimized as far as it can go and you either lose speed or specificity, I don’t think having both is possible.
Your statement piked out my interest and I went searching for what Rubisco was. My prediction is that this particular one will be cracked out soon, and at around 2045, creating disgustingly efficient variants of RuBisCO along with other photosynthesis mechanisms will be AGIs’ hot hobby.
That there are no more efficient variations of it in nature just tells us that the local minimum is really deep and that natural evolution, as it is, can’t produce anything better, not even with a billion years and 10^30 organisms serving as a “brute force lab”. It’s also the kind of problem an AGI system would tackle for purely ideological reasons, i.e. to prove that it is superior to nature.
> Demonstrate the emergence of life from chemical precursors in a laboratory setting.
> Specifically, demonstrate the unassisted emergence of self replicating RNA- and protein-based cells from a plausible primordial soup with a plausible energy source. A “cell” may be any compartment with a defined boundary.
So, right now, nobody can explain how life originated. Proving that aminoacids, DNA or RNA form, does NOT mean that this is equal to life. This is a problem that the whole field has - it still can not explain how life originated. Showing that individual components can arise spontaneously, is not the same as showing e. g. how a cell formed and so forth. Where does the encoding problem fit into any of that, for instance? You need to prove how you can assemble systems. Just having a working ribosome does not connect it to DNA as a genetic backup system; and RNA tends to be unstable. Even when you have assumptions how this works together, you need to prove that this is how things originate(d). Nobody has done so since decades. It is an unsolved problem.
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.
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
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.
They all use DNA.
But I agree that nobody has shown in the lab how any of this leads to a genetic system that can self-reproduce reliably and assemble biomolecules/metabolites. This is a missing link. Just showing how RNA or amino acids arise, says nothing about any genetic system. They can not even answer whether RNA or DNA viruses existed first; and whether these existed before organisms/cells did.
Seems a bit of an ambitious goal for a language model though! There are presumably dozens of steps before you get to an RNA-based full-blown cell, and it's only been very recently that humans have managed to make an artificial self-replicating cell of any type in the lab.
SMEs please correct the record if I'm mistaken.
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
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
I thought we already managed to successfully cryopreserve and recover small rodents like hamsters in the 50s.
Edit: See https://en.wikipedia.org/wiki/Cryopreservation#History
At least those things cannot be solved by just burning GPT tokens.
EDISON SCIENTIFIC · FUTUREHOUSE
SAM RODRIQUES · MICHAELA HINKS
https://edisonscientific.com/team
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.
That there are no more efficient variations of it in nature just tells us that the local minimum is really deep and that natural evolution, as it is, can’t produce anything better, not even with a billion years and 10^30 organisms serving as a “brute force lab”. It’s also the kind of problem an AGI system would tackle for purely ideological reasons, i.e. to prove that it is superior to nature.
> Specifically, demonstrate the unassisted emergence of self replicating RNA- and protein-based cells from a plausible primordial soup with a plausible energy source. A “cell” may be any compartment with a defined boundary.
So, right now, nobody can explain how life originated. Proving that aminoacids, DNA or RNA form, does NOT mean that this is equal to life. This is a problem that the whole field has - it still can not explain how life originated. Showing that individual components can arise spontaneously, is not the same as showing e. g. how a cell formed and so forth. Where does the encoding problem fit into any of that, for instance? You need to prove how you can assemble systems. Just having a working ribosome does not connect it to DNA as a genetic backup system; and RNA tends to be unstable. Even when you have assumptions how this works together, you need to prove that this is how things originate(d). Nobody has done so since decades. It is an unsolved problem.