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.
> Demonstrate the emergence of life from chemical precursors in a laboratory setting
Wait, isn’t this an already solved problem? I remember in the 90s school books (material written in the 80s-70s likely) it was presented as “so and so did electric discharges in an atmospheric gas mixtures and they got organic molecules” therefore the origins of life is solved. I remember thinking how cool that was. I guess the “therefore” step was sort of a lie if it’s still an open problem…
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" problem, 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" (container) 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.
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
"Your limb replacement technology is very good, but I believe humanity should transform into silicon-based beings, and so for that reason i'm out"- dragons den 2030
> 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
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.
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.
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.
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.
What seems ridiculous to me is putting together any such lists, even in math, and expecting/hoping the AI companies to solve them. The people working for the AI companies are not scientists or experts in anything outside of building LLMs. The best chance of making progress on genuinely tough (not just computationally challenging) tasks is to put advanced tools in the hands of actual scientists.
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.
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.
is it yet another vibecoded website? akin to the poster discussion, all vibecoded websites do not need to look like the same, please put some care or taste in your prompts.
Someone should make the millennium problems for AI alignment so the frontier labs will actually try to solve that problem.
You'd think that believing they are going to destroy humanity would motivate them.
They're for-profit corporations above all.
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.
> Demonstrate the emergence of life from chemical precursors in a laboratory setting
Wait, isn’t this an already solved problem? I remember in the 90s school books (material written in the 80s-70s likely) it was presented as “so and so did electric discharges in an atmospheric gas mixtures and they got organic molecules” therefore the origins of life is solved. I remember thinking how cool that was. I guess the “therefore” step was sort of a lie if it’s still an open problem…
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" problem, 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" (container) 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.
SMEs please correct the record if I'm mistaken.
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
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
You should really step outside more and touch some grass
"Your limb replacement technology is very good, but I believe humanity should transform into silicon-based beings, and so for that reason i'm out"- dragons den 2030
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
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.
Which ones are not stupid?
Cryopreservation, even though I don't care much for it.
The rubisco one is sort of not dumb, but if you actually care about carbon fixation you'd just not bother using rubisco at all instead.
Programmable Proteases is fine.
Somatic regeneration is fine.
It’s strange they are all engineering problems.
What would be your idea of a biology problem that isn't an "engineering" one?
It seems that understanding biology could be characterized as trying to figure out "how did nature engineer this".
For that matter isn't all of science this way?
Chemiosmotic effect
What aspect of that is an unsolved problem, and one that feels more fundamental rather than engineering / in need of explanation ?
Its not unsolved. It's very solved. It was not an engineering question.
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.
Right? Where's the substrates of consciousness, or the actual solutions for protein/rna folding, or the requirements for evolution?
Substrates of consciousness? You mean the neural correlates of consciousness which we already have?
As a neuroscientist: no. Not what I mean.
What else?
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
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.
> Demonstrate the ability to cryopreserve and recover live wild-type mice with high viability.
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
> 06 - Somatic limb regeneration
At least those things cannot be solved by just burning GPT tokens.
Who is this by? Who verifies the result? Is there prize money?
On the page, it says
EDISON SCIENTIFIC · FUTUREHOUSE
SAM RODRIQUES · MICHAELA HINKS
https://edisonscientific.com/team
So anyone can create a list of problems and slap the name Millennium Problems on them?
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.
Seemingly anyone can take an unordered list of things and slap "periodic table" on it even if it doesn't have any periodicity.
Now you can enjoy one man-week of rage across the remainder of your life as you won't be able to unsee it. You're welcome
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.
Slap an LLM on those and call it a day
Need to scrape the logs from some leading researchers first
It's missing some important stuff? Like creating bacteria that can produce fuels or break down plastics.
What seems ridiculous to me is putting together any such lists, even in math, and expecting/hoping the AI companies to solve them. The people working for the AI companies are not scientists or experts in anything outside of building LLMs. The best chance of making progress on genuinely tough (not just computationally challenging) tasks is to put advanced tools in the hands of actual scientists.
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.
It's inane, actually - I thought this might be something put on by an Allen Institute or some actually well-respected organization.
It's missing an obvious one: morphogenesis.
That’s number 6: limb regeneration.
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.
is it yet another vibecoded website? akin to the poster discussion, all vibecoded websites do not need to look like the same, please put some care or taste in your prompts.