Human-specific gene increases primate neocortex in the fetal marmoset | Hacker News Reader

Human-specific gene increases primate neocortex in the fetal marmoset

science.org

63 pointsNeeklo62 comments

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?

Careful - they would likely not be fuzzy nice 'people'. Far more likely avaricious sociopaths. We have enough of those.

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)

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.

> 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

2. https://journals.plos.org/plosone/article?id=10.1371/journal...

Hopefully never. I've seen a few "Planet of the Apes" movies.

Is there such a thing as degrees of gene expression? I thought it was more like a truth table

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...

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.

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.

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#...

2. https://en.wikipedia.org/wiki/Systems_biology

3. http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=home

4. https://en.wikipedia.org/wiki/SBML https://github.com/SysBioChalmers/Human-GEM

5. https://link.springer.com/article/10.1186/s13059-019-1730-3

6. https://biotechnologyforbiofuels.biomedcentral.com/articles/...

how long until we can uplift ourselves ...

Algernon wasn't happy. Let them enjoy their bliss.

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?

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.

Something to ponder.... 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?

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.

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.

I wonder if we could help them by giving them artificial hands like the ones they are testing with apes

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

Yes! another fan of the Silurian hypothesis. I know most dismiss it but there really are oddities in the geological record that are somewhat consistent with it.

Agree. No proof, I know, but such an interesting idea to think about!

Do you have any references to these oddities? Always fun to think about things like this, but can't find much about it.

oblig DNA

  Man has always assumed that he is more intelligent than dolphins because he has achieved so much--the wheel, New York, wars and so on -- while all the dolphins had ever done was muck about in the water having a good time. But, conversely, the dolphins had always believed that they were far more intelligent than man -- for precisely the same reasons.

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.

Perhaps we need a few gene edits to improve human cognition, maybe ML could help identify those.

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.

>Luckily, the experimentation with the human genome is largely forbidden.

That taboo will certainly never be broken!

Let's start doing irresponsible things because we assume "the bad guys" will be doing them anyway?

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.

> Luckily, the experimentation with the human genome is largely forbidden.

That just means singularity starts in some isolated dictatorship.

I find the ban on experimentation with the human genome rather hypocritical. We already produce and consume a vast array of synthetic chemicals that have effects on our genome. We also expose ourselves to higher than normal levels of radiation for a variety of reasons ranging from medical treatment and diagnosis to air travel. We do try to mitigate these sources of mutation but we don't ban them. I don't think genetic experimentation on human cell lines should be completely unregulated but I also don't think it should be completely banned. We're going to have to do it at some point if we want to eliminate hereditary disease or go even further and prevent a lot of the misery caused by our blind evolutionary search history.

COVID doesn't illustrate anything about human experimentation, because it has nothing to do with it.

Given the state of the science the humanity is not able to foresee the consequences of deliberate genetic changes in existing life forms.

Covid just illustrates that such changes can have disastrous consequences independent of what triggered them.

Not all changes are equal. One thing is to, say, patch a known disease-causing mutation (being sure no other changes take place). Inserting a new sequence or patching an existing sequence in a way not seen before is clearly different.

Another important dimension is whether the introduced changes are heritable and would be passed to offsprings.

I agree. We really desperately need to have experimental research in improving humanities genes. The next disease might not be so weak as COVID and could wipe almost everyone out.

Gene editing doesn't seem likely to make you immune to all diseases. They get to evolve faster than you.

Not all diseases most likely. But if we can easily rewrite our genes it's easy to stay ahead. You can easily imagine changing your genes so much there is no path for an existing disease to evolve towards it.

Gene editing doesn't imply being able to rewrite all your own genes either! Isn't mostly about embryos?

If you wanted to edit yourself you'd have the problems of reaching all your own cells, mistakes caused by edits, and what the editing process would do if it encountered a mutation in one of your cells, which of course are everywhere.

Currently, yes, it's only really feasable for embryos. But there are instances of biohackers using gene therapy to do interesting things. For example a guy cured his lactose intolerancy temporarily by gene therapy: https://hackaday.com/2018/02/14/biohacking-lactose-intoleran.... Basically what I'm trying to say is that you don't need to reach all cells to cure something. You only need to reach the relevant cells.

> I thought COVID would be a clear illustration that everyone gets but apparently this is not the case.

I thought my sarcasm was obvious but I suppose that Poe's law is at play here.

I was making a bad joke about the two fields using each other to make progress. I am under the impression that as a species we may be reaching the limits of our capacity to solve complex tasks and understand the consequences of our actions.

You don't even need modern ML to find a set of candidate SNPs for introduction, GWAS studies of educational attainment[1] give you these SNPs with weights as parameters of the statistical polygenic risk score (PRS/PGS). The problem is, intelligence is a massively polygenic trait which necessitates introduction of many SNPs (into the embryo, mind you, because most of these are likely active only during the early stages of development) to achieve life-changing effect for the person in question.

Given this knowledge, the realistic way to improve human cognition would be widely available (perhaps state-sponsored) voluntary embryo selection[2] for intelligence. Embryo selection via PGS is already being applied[3][4][5] as an optional procedure in IVF, so there is no technical risk, the only impediment for now is simply social inertia, politics and lack of large-scale investment.

Compared to this possibility cognitive enhancement in healthy adult individuals is a much harder problem: no solution is known as of now. Still, it would be interesting to speculate about realistic procedure of such type. It is unlikely that with sufficient effort we couldn't find some way to toggle[6] the correct genes and developmental processes in an adult, and deliver it via a gene therapy. Or maybe a cell therapy[7] could impart necessary neural progenitors into the mature tissue.

Given such problems at the frontiers of the known science, it is natural to think that strong ML systems operating over large -omics datasets could offer human scientists valuable help, but the progress here looks more funding-limited than technology-limited right now.

1. https://www.nature.com/articles/nrg.2017.104

2. https://www.gwern.net/Embryo-selection

3. https://www.ivfbabble.com/on-the-40th-anniversary-of-the-fir...

4. https://www.orchidhealth.com/

5. https://www.lifeview.com/

6. https://www.frontiersin.org/articles/10.3389/fncel.2018.0046...

7. https://www.pnas.org/doi/abs/10.1073/pnas.0808488105

> Given this knowledge, the realistic way to improve human cognition would be widely available (perhaps state-sponsored) voluntary embryo selection[2] for intelligence. Embryo selection via PGS is already being applied[3][4][5] as an optional procedure in IVF, so there is no technical risk, the only impediment for now is simply social inertia, politics....

The statement that a nation-wide state-sponsored embryo selection based on polygenic risk scoring for intelligence carries no risk is patently false.

Suggesting that the only impediment is "social inertia" and "politics" is intentional misinformation.

https://www.nature.com/articles/d41586-022-00787-z

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.

> 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?

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-t...

> I don't know what this could mean, beyond a tautological, "smarter would be wasteful, dumber would be dangerous"

Yes. (I like to say "evolution is a chemical tautology".)

> 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.

Ah, but that's just it: intelligence has been singled out, "only human brains are intelligent" is the prevailing dogma, eh? Are you familiar with Levin's work?

> > intelligence is ambient in living tissue

> What does this mean?

Cells think, particularly when they are organized in colonies like biofilms or organisms.

Operationally, it means things like being able to regenerate limbs and organs. In humans that is.

I can't really do a decent summary of Levin et. al.'s research this morning (I woke up hella grumpy.) But if you haven't, do check it out. (E.g. https://news.ycombinator.com/item?id=18736698 )

> A skin cell is doing something like a random walk, and thermodynamics lets it fall down energy gradients.

Only on the most physical level, same as every other chemical reaction, eh? "When you kick a rock it moves from the energy imparted by your foot. When you kick a dog it moves by it's own stored energy." I don't know if cells are little people or just robots, but their behavior isn't adequately described by thermodynamics alone, eh?

> The random walk fall down gradients theory has no explanatory power for people.

Nor for cells.

> How can the same word be useful at both levels?

It's describing the same phenomenon.

> How does a notion of cellular intelligence get aggregated/relate to/describe any notion of the emergent mind at the descriptive level of humans.

This is a fascinating question.

To be sure, Levin et. al. are going the other way, showing that what we think of as the machinery of mind is present in all cells, (and therefore IMO we should expect "mind" whatever it is to be happening in all cells too.)

Consider that every ability of a multicellular organism is an ability of its cells. Motility, digestion, homeostasis, sensory modalities, etc. This includes "mind" (if you define mind as what brains do) because "what brains do" is actually done by all cells to some degree (they all have synapses and neurotransmitters and internal computation and some kind of self-model.)

How it happens that the vision of each retina cell combines to make a subjective view, is likely how it happens that the mind of your cells creates the mind of you. In a sense they are the same thing. Dunno how it happens though.

Biofeedback research in the 60's and 70's seemed to show that you could learn to communicate with your own tissues down to individual cells.

> Biofeedback research in the 60's and 70's seemed to show that you could learn to communicate with your own tissues down to individual cells.

Trying to find more on this. Do you have a link or a good search term to point me in the right direction? (Specifically regarding affecting individual cells; brain state biofeedback overwhelms the search results)

I don't, sorry. It was already obscure in the late 80's / early 90's when I read about it. "Fringe"

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

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.

I think you might benefit from understanding what this means:

https://www.urbandictionary.com/define.php?term=%2FS

ahha terribly terribly sorry!

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.

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.

You're the only person who brought race into this and that says way more about you than anyone else.

> 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.

This is, in fact, false. Hope this helps.

If I told you a way it was true - people with phenylketonuria become "less intelligent" if their environment contains Diet Coke - you wouldn't take that as a win, because by "genetic differences" you mean "science says I'm better than this other guy in a way they can never overcome".

Or possibly you're getting info from people who think "heritable" means "genetic", which it doesn't.

> you wouldn't take that as a win, because by "genetic differences" you mean "science says I'm better than this other guy in a way they can never overcome"

Can I say Jakob Ingebrigsten is better than me (at middle distance running) in a way I can never overcome due to genetic differences?

I am fairly sure someone with my genetics cannot run a 4 minute mile, and the guy does that for fun. But perhaps I am wrong and given the right environment every human being is capable of running a 4 minute mile?

Doesn't seem like the most obvious explanation, considering you don't have either of your genetics on hand and have existed in different environments since you were zygotes.

All the other stuff (environment, diet, mother's diet… even training) is more likely to be it because it happened more recently.

Also, you don't become a professional runner because you're the world's best at running. You become a runner because you're not even better at something else. That's called "comparative advantage".

> All the other stuff (environment, diet, mother's diet… even training) is more likely to be it because it happened more recently.

And yet, the evidence contradicts you: https://bmcgenomics.biomedcentral.com/articles/10.1186/s1286...

Mind you, the (many variables) in the environment certainly have an effect. And without training you just can't reach elite performance. But most humans out of the womb, can't run a 4 minute mile regardless of training regimen over their lives.

I pick that number because it's at the edge of human performance. No woman in the world, out of the many impressive athletes who have tried, ever got close - the record is 4:12 by the incredible Sifan Hassan. Only a few hundred men in the US have been able to achieve it. Was it the environment, their mother's diet or the patriarchy that allowed these men - but not the many thousands, (millions?) of other men and women who tried- to run under 4 minutes in the mile?

I'm sure you agree physical ability depends on genetics in certain cases. No human being can reach the top speed of the average lion, and that's purely due to genes.

The idea that genetic differences cease to matter for peak potential performance when we talk about individuals of the same species, flies in the face of all the sports science evidence.

Occam's razor makes genetics the obvious explanation for things everyone who ever did sports in school has observed: certain kids can dunk with minimal training (height, fast-twitch muscle fibers) and others can't touch the rim, certain kids can lap others before they ever do any sort of endurance training, and once they do, even very talented kids run out of breath trying to keep up with the best given equal training, etc.

Most environment effects can be extremely detrimental in rare cases (mother's diet impacting embryo/fetus development, poor early childhood nutrition), but once we're out of the womb and healthy, there are massive differences and nothing indicates running a 4 minute mile is about whose mum ate the best breakfast.

P.S.: Most of this "genes, evolution theory, speciation, yes all true, but humans are all the same, basically" ideology stems from a good place - don't want to repeat the eugenics and similar bullshit of the last century. You can do both. Defend humans rights and equal treatment for all humans, with the understanding that individuals are different and many of those differences are determined by their genes.

It's a mystery to me why this paper is claiming that environment is "nurture" or that twin studies prove things are caused by genetics; neither of these are true because your mother's womb is all of environment, diet, not (your) genetics, and not controlled by a twin study.

You're welcome to invent some kind of intervention study where you edit one twin's genes and not the other though. Short of that, genetics studies are interesting but not good at finding reliable evidence for much. Imagine using GWAS to analyze a computer program - it'd tell you one version of it has a new feature because it has a letter 'p' in one position of the source code.

The other issue is that genetics don't typically make you better/worse in general, they make you more adapted to an environment. So the main reason to know them is to find interventions where you improve that environment.

There isn't much need for that for sprinting, which I guess makes it better as a sport. For long distance running there's, well, owning a car. Though I remember hearing about this tribe of long-distance runners, who adapted to their lifestyle not through genetic traits but cultural ones:

https://www.runnersworld.com/gear/a20783981/study-running-fo...

The best examples of genetic traits that do differ in humans are ones we got from elsewhere; humans really are extremely closely related for a species and haven't had much time to invent a lot of them. We got the Tibetan adaption to mountains and the European/Asian straight hair and cold adaption by hooking up with other hominins.

I myself am carrying a rare genetic disease (LHON) which I have no symptoms of, so even having a copy of my whole genome tells you a lot less than just meeting me.

> neither of these are true because your mother's womb is all of environment, diet, not (your) genetics, and not controlled by a twin study.

> you're welcome to invent some kind of intervention study where you edit one twin's genes and not the other though.

And yet all of these criticisms are just saying we don't have a way to perfectly isolate the genetic effect. These studies still provide evidence for the impact of genes on whatever they are studying, even if the conditions in the mother's womb are also factor. The position that "everything but genes explains the observed differences" is the irrational one given the evidence.

> The other issue is that genetics don't typically make you better/worse in general, they make you more adapted to an environment.

I'm not sure why you are bringing this up? I didn't say anything about being better/worse in general (whatever that means)? I am talking about being able to run a 4 minute mile on Earth's surface (1 atm, 15-30 celsius, etc.)

> Though I remember hearing about this tribe of long-distance runners, who adapted to their lifestyle not through genetic traits but cultural ones

And yet, it's trivial to find papers mentioning how more genetic analysis is required, but there is evidence for genetic adaptation:

"The only genetic analysis carried out specifically in Tarahumara runners showed a striking enrichment in genes related to the production of the extracellular matrix of tendons and muscles in a gene ontology analysis (41). This genetic profile could provide the mechanical advantages for the foot strike that we mentioned above."

"Remarkably, it has been found that physical training in hypoxia can upregulate NKC activating molecules (52). And indeed, the activator gene, KIR2SD5, has a differential expression among the Tarahumara (19)."

https://www.germanjournalsportsmedicine.com/archiv/archive-2...

> The best examples of genetic traits that do differ in humans are ones we got from elsewhere; humans really are extremely closely related for a species and haven't had much time to invent a lot of them.

You are talking about traits such as Tibetan adaptation to high elevation - something which requires genetic variability and selection pressure - whereas I am simply talking about the fact that there is genetic variability at the individual level that impacts performance.

Absence of a large number conserved genetic traits in specific populations, does not imply "human genetic differences are irrelevant at the individual level".

I am not claiming Norwegians as a whole have developed the "superhuman middle-distance running trait". There likely has been no (or little) selection pressure to do so, so the "trait" does not exist as something that is conserved in a specific population.

What exists is a lot of genetic variation that allows for some individuals (such as Jakob Ingebrigtsen) to be significant outliers when it comes to running a mile race. Because. of. his. genes.

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