8 ms·

Human-specific gene increases primate neocortex in the fetal marmoset

63 points by Neeklo 4y ago

throwaway4aday 4y ago
So how long until we can "uplift" these marmosets to near human intelligence? Also, does increased expression of this gene in humans result in further development of the neocortex?
- JoeAltmaier 4y ago
  Careful - they would likely not be fuzzy nice 'people'. Far more likely avaricious sociopaths. We have enough of those.
  - deleted 4y ago
    [deleted]
- Neeklo 4y ago
  In a later paper (2021) they tried the same experiment in mice: the paper claim that together with neocortex expansion, the behaviour of mice was altered( higher memory flexibility and reduced anxiety levels). This is still not what you're asking but quite interesting in my opinion! To get to your question (to which I really don't know the answer!): from my understanding, the mechanisms through wigh arhgap11b works are still not clear, so the simple overexpression might not be the answer for mega-brains! (sometimes these genes are regulated upstream so you cannot force them really, or on the other end, overexpression of genes often brings other unwanted consequences)
  - daniel-cussen 4y ago
    Yeah but more energy use, and further they were better at the challenges set so far, no the challenges to come as the experimenters adapted to the change.
  - sinenomine 4y ago
    > the behaviour of mice was altered( higher memory flexibility and reduced anxiety levels). Notably, this isn't the first time there was a success in murine cognitive enhancement via genetic engineering. There was a promising line of research targeting NR2B overexpression: [1][2]. There seems to be an unfortunate lack of funding and research in this area. 1. https://www.nature.com/articles/43432 https://www.nature.com/articles/43432 2. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007486 https://journals.plos.org/plosone/article?id=10.1371/journal...
- antisthenes 4y ago
  Hopefully never. I've seen a few "Planet of the Apes" movies.
- brailsafe 4y ago
  Is there such a thing as degrees of gene expression? I thought it was more like a truth table
  - throwaway4aday 4y ago
    Here's an interesting article that also explains how multiple copies of genes can alter certain traits https://www.newscientist.com/article/dn12381-duplicate-genes-help-humans-go-the-extra-mile/ https://www.newscientist.com/article/dn12381-duplicate-genes...
  - 331c8c71 4y ago
    There are many mechanisms that influence the gene transcription and/or availability of gene products the keyword is "gene expression regulation". One way that happens for instance is packing/unpacking of the chromatin (genes in densely packed chromatin are not accessible). The trick is that chromatin can easily pack or unpack depending on what is going on around. Another simpler possibility is that there is a molecule that binds (stochastically) near promoter region (the place from which the gene is being transcribed) and hence influences the rate at which the gene is transcribed.
  - mnw21cam 4y ago
    Yes, definitely. Like most things that evolve over time (like laws and spaghetti code), the mechanics of gene regulation are incredibly complicated, diverse, and messy. It's an analogue system too.
  - sinenomine 4y ago
    There is a whole multitude of gene expression regulation mechanisms, which evolution successfully used to express whole nonlinear dynamical systems[1] appropriate to the task. These systems are partially understood[2] (there are promoter libraries[3], known cis- and trans- regulatory elements, activators and repressors, etc) and can be simulated[4][5] well enough to be of use for tailoring[6] single-celled organisms to a specific biotechnological task at hand. 1. https://en.wikipedia.org/wiki/Regulation_of_gene_expression#Circuitry https://en.wikipedia.org/wiki/Regulation_of_gene_expression#... 2. https://en.wikipedia.org/wiki/Systems_biology https://en.wikipedia.org/wiki/Systems_biology 3. http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=home http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=home 4. https://en.wikipedia.org/wiki/SBML https://en.wikipedia.org/wiki/SBML https://github.com/SysBioChalmers/Human-GEM https://github.com/SysBioChalmers/Human-GEM 5. https://link.springer.com/article/10.1186/s13059-019-1730-3 https://link.springer.com/article/10.1186/s13059-019-1730-3 6. https://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-019-1518-4 https://biotechnologyforbiofuels.biomedcentral.com/articles/...
- nathias 4y ago
  how long until we can uplift ourselves ...
- 0des 4y ago
  Algernon wasn't happy. Let them enjoy their bliss.
  - sinenomine 4y ago
    Ah, the good old "argument from media". Someone should bring up black mirror as well, surely there is some fitting platitude to be brought from that one ... again. ... What if we uplifted a species enough for its living representative to express their gratitude to us in our own language? Is it completely impossible, or merely unlikely?
    - astrange 4y ago
      If you uplifted a mouse I think it'd mainly complain about its two year lifespan and the difficulty of feeding its new brain with a mouse diet and digestive system. Although, at least mice are omnivores and don't have to build their brains out of hay like a guinea pig.
axg11 4y ago
Biotech/genomics and AI/ML are following very interesting parallel trajectories over the last ~10 years. In biotech, we have developed incredible tools: DNA editing (CRISPR), synthesis, and sequencing. We have a lot of tools but we haven't cracked systems level understanding yet. In AI/ML, we have developed algorithms that can ace tasks thought impossible just 15 years ago. We have a hunch of how and why they work, but we lack deep understanding.
- PartiallyTyped 4y ago
  Perhaps we need a few gene edits to improve human cognition, maybe ML could help identify those.
  - deleted 4y ago
    [deleted]
  - 331c8c71 4y ago
    ML methods and statistics are routinely used in genomics research. Luckily, the experimentation with the human genome is largely forbidden. The consequences of unbridled changes in genetic sequences include truly disastrous scenarios. I thought COVID would be a clear illustration that everyone gets but apparently this is not the case.
    - idiotsecant 4y ago
      >Luckily, the experimentation with the human genome is largely forbidden. That taboo will certainly never be broken!
      - 331c8c71 4y ago
        Let's start doing irresponsible things because we assume "the bad guys" will be doing them anyway?
      - 331c8c71 4y ago
        On a more constructive note, I think non-germline targeted gene editing is OK-ish if 1) the goal is to cure or alleviate some really serious diseases, 2) the mechanism of the disease and the prospective treatment are widely believed to be well understood. Stepping out to do experimental genome changes based on outputs from some black-box "AI" is a recipe for a disaster if you ask me. Especially so if the goal is to find "enhancements" for perfectly normal human beings.
andrewclunn 4y ago
This sort of research is incredibly dangerous, as it could lead to the (clearly false) belief that measured differences in cognitive ability between different human sub-groups is also based in genetic differences. Also, if apes were created with human level intelligence then the lines of "human rights" might be tied inextricably to quantified intelligence. We must outlaw such research and brand it as "racist" immediately (on a cultural level) to prevent going down a scientifically justified social darwinian path toward distopia /s
- Neeklo 4y ago
  Without arguing on the specifics of this case, I do not think that the answer is "ban all of research that can be read as racist". This -seems to me- would be acting on symptoms and not causes of a deeper issue, and could actually end up in much worst consequences.
  - andrewclunn 4y ago
    I think you might benefit from understanding what this means: https://www.urbandictionary.com/define.php?term=%2FS https://www.urbandictionary.com/define.php?term=%2FS
    - Neeklo 4y ago
      ahha terribly terribly sorry!
- smolder 4y ago
  Why make a straw man just so you can sarcastically mock it? At least wait for someone to express a real opinion you disagree with. This isn't a good basis for discussion nor very relevant.
  - andrewclunn 4y ago
    Considering the first comment missed that it was sarcasm, I think I hit a recurring sort of argument right on the head. As far as relevancy, I think the the practice of modifying primate genes, specifically to make them more human like in cognitive ways, and then aborting them to prevent the true impact of the development being studied (and to avoid anyone coming after them for human / animal rights violations) is very relevant with this sort of research.
carapace 4y ago
There's an argument to be made that evolution has intelligence "on tap" as it were, or in other words, evolving systems have as much intelligence as is adaptive. Wolfram and others have shown that (what we think of as) complex computation arises commonly and naturally in even moderately complex and interconnected systems. Far from being rare, the machinery to support intelligence arises in most energy gradients. (Roughly speaking there are four regimes: static, dull, Life, chaotic.) Michael Levin et. al. are busy showing how all living tissue has agency and intelligence. (E.g. take some skin cells and put them in the right conditions and they turn into little critters and creep around!) The biomolecular machinery that neurons use to think is present in all multicellular tissue. So, intelligence is ambient in living tissue (and has been for N billion years, where N is roughly 4 I think?) - - - - I got this far and forgot what my original point was... I swear it was relevant.
- nh23423fefe 4y ago
  > evolving systems have as much intelligence as is adaptive I don't know what this could mean, beyond a tautological, "smarter would be wasteful, dumber would be dangerous" But every property of an animal could be described that way. height, weight, speed, etc. intelligence isn't singled out that way, so the description doesn't provide insight or leverage. > intelligence is ambient in living tissue What does this mean? A skin cell is doing something like a random walk, and thermodynamics lets it fall down energy gradients. How does a notion of cellular intelligence get aggregated/relate to/describe any notion of the emergent mind at the descriptive level of humans. The random walk fall down gradients theory has no explanatory power for people. How can the same word be useful at both levels?
  - throwaway4aday 4y ago
    I'm not sure that all of the behaviour that Levin has observed or been able to produce can be explained by a random walk or following a gradient https://www.quantamagazine.org/cells-form-into-xenobots-on-their-own-20210331/ https://www.quantamagazine.org/cells-form-into-xenobots-on-t...
  - carapace 4y ago
zw123456 4y ago
Something to ponder.... https://whalesanctuaryproject.org/the-worlds-most-intelligent-species/ https://whalesanctuaryproject.org/the-worlds-most-intelligen... > "we’ve known that the neocortex of a whale or dolphin brain has more folds than ours. All those folds mean that the surface area is greater and therefore may have more units to process information." Maybe they know something we don't?
- dmitriy_ko 4y ago
  It could be that dolphins are smarter than humans. Dolphins didn't build civilization, but it could be because they don't have flexible enough limbs for tool making. Maybe humans just got lucky with a combination of relatively high intelligence, language and flexible limbs.
  - upwardbound 4y ago
    Also you can't make fire underwater (setting aside elements like potassium that aren't readily obtainable in large quantities the way wood and coal are). This makes it a lot more difficult for an aquatic species to have an Industrial Revolution. I guess in theory you could burn aquatic plants like kelp, and burn them at the surface, building 2D floating factories at the surface of the ocean, but this sounds vastly more difficult than what we humans did. You'd have trouble finding enough kelp to burn, and the waves of the ocean would mean that your factories couldn't be on a stable foundation. I suspect you'd also have trouble making a spark for ignition, and you might have to be very patient and wait for a lightning strike or something.
    - aszantu 4y ago
      I wonder if we could help them by giving them artificial hands like the ones they are testing with apes
  - zw123456 4y ago
    They used to be land mammals. Maybe they had a civilization, but they ruined the climate with it, then evolved to be sea mammals but kept their intelligence? https://en.wikipedia.org/wiki/Silurian_hypothesis https://en.wikipedia.org/wiki/Silurian_hypothesis

63 points by Neeklo 4y ago

So how long until we can "uplift" these marmosets to near human intelligence? Also, does increased expression of this gene in humans result in further development of the neocortex?

JoeAltmaier 4y ago
Careful - they would likely not be fuzzy nice 'people'. Far more likely avaricious sociopaths. We have enough of those.
- deleted 4y ago
  [deleted]
Neeklo 4y ago
In a later paper (2021) they tried the same experiment in mice: the paper claim that together with neocortex expansion, the behaviour of mice was altered( higher memory flexibility and reduced anxiety levels). This is still not what you're asking but quite interesting in my opinion! To get to your question (to which I really don't know the answer!): from my understanding, the mechanisms through wigh arhgap11b works are still not clear, so the simple overexpression might not be the answer for mega-brains! (sometimes these genes are regulated upstream so you cannot force them really, or on the other end, overexpression of genes often brings other unwanted consequences)
- daniel-cussen 4y ago
  Yeah but more energy use, and further they were better at the challenges set so far, no the challenges to come as the experimenters adapted to the change.
- sinenomine 4y ago
  > the behaviour of mice was altered( higher memory flexibility and reduced anxiety levels). Notably, this isn't the first time there was a success in murine cognitive enhancement via genetic engineering. There was a promising line of research targeting NR2B overexpression: [1][2]. There seems to be an unfortunate lack of funding and research in this area. 1. https://www.nature.com/articles/43432 https://www.nature.com/articles/43432 2. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007486 https://journals.plos.org/plosone/article?id=10.1371/journal...
antisthenes 4y ago
Hopefully never. I've seen a few "Planet of the Apes" movies.
brailsafe 4y ago
Is there such a thing as degrees of gene expression? I thought it was more like a truth table
- throwaway4aday 4y ago
  Here's an interesting article that also explains how multiple copies of genes can alter certain traits https://www.newscientist.com/article/dn12381-duplicate-genes-help-humans-go-the-extra-mile/ https://www.newscientist.com/article/dn12381-duplicate-genes...
- 331c8c71 4y ago
  There are many mechanisms that influence the gene transcription and/or availability of gene products the keyword is "gene expression regulation". One way that happens for instance is packing/unpacking of the chromatin (genes in densely packed chromatin are not accessible). The trick is that chromatin can easily pack or unpack depending on what is going on around. Another simpler possibility is that there is a molecule that binds (stochastically) near promoter region (the place from which the gene is being transcribed) and hence influences the rate at which the gene is transcribed.
- mnw21cam 4y ago
  Yes, definitely. Like most things that evolve over time (like laws and spaghetti code), the mechanics of gene regulation are incredibly complicated, diverse, and messy. It's an analogue system too.
- sinenomine 4y ago
  There is a whole multitude of gene expression regulation mechanisms, which evolution successfully used to express whole nonlinear dynamical systems[1] appropriate to the task. These systems are partially understood[2] (there are promoter libraries[3], known cis- and trans- regulatory elements, activators and repressors, etc) and can be simulated[4][5] well enough to be of use for tailoring[6] single-celled organisms to a specific biotechnological task at hand. 1. https://en.wikipedia.org/wiki/Regulation_of_gene_expression#Circuitry https://en.wikipedia.org/wiki/Regulation_of_gene_expression#... 2. https://en.wikipedia.org/wiki/Systems_biology https://en.wikipedia.org/wiki/Systems_biology 3. http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=home http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=home 4. https://en.wikipedia.org/wiki/SBML https://en.wikipedia.org/wiki/SBML https://github.com/SysBioChalmers/Human-GEM https://github.com/SysBioChalmers/Human-GEM 5. https://link.springer.com/article/10.1186/s13059-019-1730-3 https://link.springer.com/article/10.1186/s13059-019-1730-3 6. https://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-019-1518-4 https://biotechnologyforbiofuels.biomedcentral.com/articles/...
nathias 4y ago
how long until we can uplift ourselves ...
0des 4y ago
Algernon wasn't happy. Let them enjoy their bliss.
- sinenomine 4y ago
  Ah, the good old "argument from media". Someone should bring up black mirror as well, surely there is some fitting platitude to be brought from that one ... again. ... What if we uplifted a species enough for its living representative to express their gratitude to us in our own language? Is it completely impossible, or merely unlikely?
  - astrange 4y ago
    If you uplifted a mouse I think it'd mainly complain about its two year lifespan and the difficulty of feeding its new brain with a mouse diet and digestive system. Although, at least mice are omnivores and don't have to build their brains out of hay like a guinea pig.

axg11 4y ago

Biotech/genomics and AI/ML are following very interesting parallel trajectories over the last ~10 years. In biotech, we have developed incredible tools: DNA editing (CRISPR), synthesis, and sequencing. We have a lot of tools but we haven't cracked systems level understanding yet. In AI/ML, we have developed algorithms that can ace tasks thought impossible just 15 years ago. We have a hunch of how and why they work, but we lack deep understanding.

PartiallyTyped 4y ago
Perhaps we need a few gene edits to improve human cognition, maybe ML could help identify those.
- deleted 4y ago
  [deleted]
- 331c8c71 4y ago
  ML methods and statistics are routinely used in genomics research. Luckily, the experimentation with the human genome is largely forbidden. The consequences of unbridled changes in genetic sequences include truly disastrous scenarios. I thought COVID would be a clear illustration that everyone gets but apparently this is not the case.
  - idiotsecant 4y ago
    >Luckily, the experimentation with the human genome is largely forbidden. That taboo will certainly never be broken!
    - 331c8c71 4y ago
      Let's start doing irresponsible things because we assume "the bad guys" will be doing them anyway?
    - 331c8c71 4y ago
      On a more constructive note, I think non-germline targeted gene editing is OK-ish if 1) the goal is to cure or alleviate some really serious diseases, 2) the mechanism of the disease and the prospective treatment are widely believed to be well understood. Stepping out to do experimental genome changes based on outputs from some black-box "AI" is a recipe for a disaster if you ask me. Especially so if the goal is to find "enhancements" for perfectly normal human beings.

andrewclunn 4y ago

This sort of research is incredibly dangerous, as it could lead to the (clearly false) belief that measured differences in cognitive ability between different human sub-groups is also based in genetic differences. Also, if apes were created with human level intelligence then the lines of "human rights" might be tied inextricably to quantified intelligence. We must outlaw such research and brand it as "racist" immediately (on a cultural level) to prevent going down a scientifically justified social darwinian path toward distopia /s

Neeklo 4y ago
Without arguing on the specifics of this case, I do not think that the answer is "ban all of research that can be read as racist". This -seems to me- would be acting on symptoms and not causes of a deeper issue, and could actually end up in much worst consequences.
- andrewclunn 4y ago
  I think you might benefit from understanding what this means: https://www.urbandictionary.com/define.php?term=%2FS https://www.urbandictionary.com/define.php?term=%2FS
  - Neeklo 4y ago
    ahha terribly terribly sorry!
smolder 4y ago
Why make a straw man just so you can sarcastically mock it? At least wait for someone to express a real opinion you disagree with. This isn't a good basis for discussion nor very relevant.
- andrewclunn 4y ago
  Considering the first comment missed that it was sarcasm, I think I hit a recurring sort of argument right on the head. As far as relevancy, I think the the practice of modifying primate genes, specifically to make them more human like in cognitive ways, and then aborting them to prevent the true impact of the development being studied (and to avoid anyone coming after them for human / animal rights violations) is very relevant with this sort of research.

carapace 4y ago

There's an argument to be made that evolution has intelligence "on tap" as it were, or in other words, evolving systems have as much intelligence as is adaptive. Wolfram and others have shown that (what we think of as) complex computation arises commonly and naturally in even moderately complex and interconnected systems. Far from being rare, the machinery to support intelligence arises in most energy gradients. (Roughly speaking there are four regimes: static, dull, Life, chaotic.) Michael Levin et. al. are busy showing how all living tissue has agency and intelligence. (E.g. take some skin cells and put them in the right conditions and they turn into little critters and creep around!) The biomolecular machinery that neurons use to think is present in all multicellular tissue. So, intelligence is ambient in living tissue (and has been for N billion years, where N is roughly 4 I think?) - - - - I got this far and forgot what my original point was... I swear it was relevant.

nh23423fefe 4y ago
> evolving systems have as much intelligence as is adaptive I don't know what this could mean, beyond a tautological, "smarter would be wasteful, dumber would be dangerous" But every property of an animal could be described that way. height, weight, speed, etc. intelligence isn't singled out that way, so the description doesn't provide insight or leverage. > intelligence is ambient in living tissue What does this mean? A skin cell is doing something like a random walk, and thermodynamics lets it fall down energy gradients. How does a notion of cellular intelligence get aggregated/relate to/describe any notion of the emergent mind at the descriptive level of humans. The random walk fall down gradients theory has no explanatory power for people. How can the same word be useful at both levels?
- throwaway4aday 4y ago
  I'm not sure that all of the behaviour that Levin has observed or been able to produce can be explained by a random walk or following a gradient https://www.quantamagazine.org/cells-form-into-xenobots-on-their-own-20210331/ https://www.quantamagazine.org/cells-form-into-xenobots-on-t...
- carapace 4y ago

zw123456 4y ago

Something to ponder.... https://whalesanctuaryproject.org/the-worlds-most-intelligent-species/ https://whalesanctuaryproject.org/the-worlds-most-intelligen... > "we’ve known that the neocortex of a whale or dolphin brain has more folds than ours. All those folds mean that the surface area is greater and therefore may have more units to process information." Maybe they know something we don't?

dmitriy_ko 4y ago
It could be that dolphins are smarter than humans. Dolphins didn't build civilization, but it could be because they don't have flexible enough limbs for tool making. Maybe humans just got lucky with a combination of relatively high intelligence, language and flexible limbs.
- upwardbound 4y ago
  Also you can't make fire underwater (setting aside elements like potassium that aren't readily obtainable in large quantities the way wood and coal are). This makes it a lot more difficult for an aquatic species to have an Industrial Revolution. I guess in theory you could burn aquatic plants like kelp, and burn them at the surface, building 2D floating factories at the surface of the ocean, but this sounds vastly more difficult than what we humans did. You'd have trouble finding enough kelp to burn, and the waves of the ocean would mean that your factories couldn't be on a stable foundation. I suspect you'd also have trouble making a spark for ignition, and you might have to be very patient and wait for a lightning strike or something.
  - aszantu 4y ago
    I wonder if we could help them by giving them artificial hands like the ones they are testing with apes
- zw123456 4y ago
  They used to be land mammals. Maybe they had a civilization, but they ruined the climate with it, then evolved to be sea mammals but kept their intelligence? https://en.wikipedia.org/wiki/Silurian_hypothesis https://en.wikipedia.org/wiki/Silurian_hypothesis