Posted by artninja1988 2 days ago
Rather: Someone should make the millennium problems for human alignment so the top researchers will actually try to solve that problem. :-)
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.
I hope you are right.
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.
I think some of the items on the list are also way less likely to be worked on (like cryogenics) than others, because they really require some heavy infrastructure to iterate. My money for which of these gets cracked with help of an AI would be rubisco, that can be quite effectively worked on in a closed loop lab fashion with a standard lab or CRO.
Biology is a really really big field. Many problems in biology are that of math and coding. Just as a simple example look at the golden ratio in living organisms. Biology follows a lot of different algorithms because they are energy efficient and come with massive secondary benefits.
What is this example meant to illustrate?
>The golden ratio (≈ 1.618) and its related golden angle (137.5°) show up in nature because they maximize space, exposure, and flow.
The golden ratio is an algorithm, but it is also a natural law that systems of many different scales follow. Wherever we look we find examples of it. Without this algorithm the world is a much harder place to explain.
What many scientists starting to look for is these algorithms we have not identified in natural systems as an explanatory means of their workings. Also because they are algorithms they are things we can put into computer systems to increase efficiency, or may naturally emerge from evolutionary learning systems like AI in what we call emegence.
the better direction in my opinion, is the mutual reinforcement of coupled dynamic systems, that ends up giving us metabolism.
>There is no convincing evidence that the golden ratio is linked to idealized human proportions or facial beauty. There is currently no evidence to support the use of the golden ratio in orthognathic or facial aesthetic/reconstructive surgical planning or analysis of results.
This is about peoples faces. What I listed was about things like available surface area for things like chemical reactions and mixing, you know things that are mathematically calculatable. Much in the same manner a hexagon is an optimal low energy shape, hence we see lots of them in nature too.
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.
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"
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.
> 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
> 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.
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.
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.
Actually, we have quite a bit of evidence to evidence pointing at the order of development based on how strongly conserved some critical features of biochemistry.
The core component of ribosomes (which make proteins) is made from RNA called ribozymes. Other things like RNase P, self-splicing introns, the RNA cores of the spliceosome, and the fact that most central metabolic cofactors (ATP, NAD, FAD, coenzyme A) have ribonucleotide handles points to RNA as the initial building block, before viruses or archae or prokaryotes were even born.
It wasn’t until ribonucleotide reductase gets involved that RNA becomes DNA. DNA swaps uracil for thymine making the genome more error-resistant and a double helix to get stability over reactivity, as a clear evolutionary strategy because DNA doesn’t form like RNA does.
The core of the RNA world hypothesis is a ton of experiments that find that RNA and amino acids are stable in many different chemical conditions which cover a wide range of what the early earth would have looked like along with observed amino acids on outer space objects like comets and asteroids. What we don’t have is an experiment demonstrating how RNA becomes self replicating with the addition of amino acids, which would be one of the last steps to showing how life likely formed.
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.
I really really recommend looking up Michael Levins bio work on intelligence at the cellular and organ level.
His most recent work is starting to touch on some pretty far out concepts. And I should note, that he does not state they are true or not, but they are attempting to make empirical methods on testing them.
One of the concepts they are looking at is "math as an actual thing" and that some simple algorithms have new deeper behaviors that we're just finding now. The hypothesis is that over the eons life has probed mathematics at scales humanity cannot even begin to imagine and is exploiting this deep algorithmic efficiency in accomplishing any number of tasks. These algorithms could help explain the missing links.
I'd suggest starting with some of his older work to see they are a credentialed research scientist and not making up 'woo' whole cloth.
He seems to be essentially the only biologist that hackernews knows and he always (always!) comes up in biology discussion. I’m wondering how this particular situation arose.
Dogma in science tends to blind people, and when a field starts slowing down and running into things we cannot address then we have to start looking at what we should be questioning.
I’m a working research biologist, and I’m genuinely curious how he became so well known among the hackernews slice of the public. He seems to have hit on some very effective combination of research interests and public communication strategy.
I suspected it was the Lex Fridman podcast appearances, but I wasn’t sure if that was how most people became aware of him.
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…
We don't even know if Miller or Urey themselves would have (or did) frame their results that way. The honest framing is 'hey this is one way to form amino acids, and maybe that pathway is reflective of the origin of life, but that supposition remains conjecture on our part.'
still not all the way to something alive-like
I recently watched this video on the topic https://www.youtube.com/watch?v=OsXGgrXwllc