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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

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.

shevy-java 6d ago
> 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.
- HarHarVeryFunny 6d ago
  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.
- pixl97 6d ago
  >They all use DNA. 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.
  - bglazer 6d ago
    I’m curious how you found Michael’s work? Like what led you to familiarize yourself with his research? 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.
    - pixl97 6d ago
      It's been long enough that I'm not really sure. It's every time I see some of his work the way he looks at problems always intrigued me. 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.
      - bglazer 6d ago
        How do you keep up to date with his work?
        pixl97 6d ago
        Just searching it up in YouTube is a good starting place. He has visited a number of different podcasts. Then from there you can drill down into papers on the interesting things.
        bglazer 5d ago
        Thanks, I was more asking from your perspective. 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.
        randomImmigrant 5d ago
- throwup238 5d ago
  > 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.

shevy-java 6d ago

> 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.

HarHarVeryFunny 6d ago
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.
pixl97 6d ago
>They all use DNA. 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.
- bglazer 6d ago
  I’m curious how you found Michael’s work? Like what led you to familiarize yourself with his research? 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.
  - pixl97 6d ago
    It's been long enough that I'm not really sure. It's every time I see some of his work the way he looks at problems always intrigued me. 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.
    - bglazer 6d ago
      How do you keep up to date with his work?
      - pixl97 6d ago
        Just searching it up in YouTube is a good starting place. He has visited a number of different podcasts. Then from there you can drill down into papers on the interesting things.
        bglazer 5d ago
        Thanks, I was more asking from your perspective. 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.
        randomImmigrant 5d ago
throwup238 5d ago
> 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.