The most frustrating thing about the current state of our genomic knowledge and capabilities is the gulf between them and what's actually available in the world. I feel like theorem and praxis have a vast gulf between them, and although we keep progressing on the theorem side, the praxis side has essentially zero serious investment or effort behind it.
Like we've been able to CRISPR single genes for soooo long now. But do you see any governments anywhere in the world doing a crash program to CRISPR the "you need 30% less sleep" SNP into their populations at large? Not at all. But just think of the productivity and economic growth potential! Governments should be falling over themselves to do this at scale for free to any citizen that wants it. As a parent, think of being able to give your kid literally 30% more conscious life, right off the bat, every day they're alive! It would be like saving 4k+ lifetimes every single year, just in the US.
And as far as I know, labs aren't GWAS-ing "sleeplessness" more generally, to do even better than that 30%. Certainly not in any way that's going to let it be one of the menu items from one of the gengineering / embryo selection startups like Orchid. Yet arguably, this is probably the highest possible value thing we could drive in humans with gengineering, and we could have been doing it a decade ago, at scale, and this is just *one* example.
> Like we've been able to CRISPR single genes for soooo long now. But do you see any governments anywhere in the world doing a crash program to CRISPR the "you need 30% less sleep" SNP into their populations at large?
What's the downside? Do we even know it?
Hint: we don't even really understand why we sleep in the first place.
Not much downsides - one of my best friends has this mutation, and loooong have I envied him. And with his 3-4 hours a night, he was a competitive athlete and a high-performer at work and a founder in the non-profit domain, and much else.
I dug up a Pubmed paper on these folks once, and there basically wasn't any appreciable downsides.
And anyways, the downsides matter a lot less than the option *even being available.* I'd pay 500k to put this in some of my embryos, conservatively, and I'll happily take the downside risk. But am I able to do that, anywhere in the world? Nope. Am I able to specify "highest IQ possible," "tall and blonde and attractive," "high happiness set point," "high conscientiousness" or anything else useful that I'd be happy to pay for? Nope. We're getting to the bare minimum regions of "you can pay for a 2-5 IQ point buff," but nothing else on anything that matters.
Open up gengineering *somewhere*, anywhere in the world, and let the parents assume whatever risk profile they're comfortable with. But no, that's way too much to ask, apparently.
Meanwhile, there is zero limitation on short, sickly, dumb, ugly, unemployed, or any other maladaptive combination of traits deciding to have a kid together, which has much larger and easier to quantify risks in the child and to society, but it's totally fine. But let some parents assume the risks for gengineering? That's beyond the pale!
I've legit thought of it - I'd spend a few million USD trying to get the "sleep less" SNP into a CRISPR-able state into my own embryos, so why not take on some other customers at the same time and amortize some of those costs?
I actually don't think a few mil would cut it, though, and I really don't want to do another startup right now, especially one that's going to be pretty limited in final size and upside.
But if you know of one that'll do it for about that level of investment, please do let me know. I didn't think Prospera even had a gengineering company at all? Orchid is SF, and doesn't do anything actually interesting / worth it to my mind.
"Meanwhile, there is zero limitation on short, sickly, dumb, ugly, unemployed, or any other maladaptive combination of traits deciding to have a kid together, which has much larger and easier to quantify risks in the child and to society, but it's totally fine."
I am suspicious of the meme that a person's height has any significance in the modern world. Plus, I doubt there are human genes for unemployment.
I'm assuming you're either a woman, or have never used dating apps. If you want high status grandkids, you want height for your male descendants with zero doubt.
"I'm assuming you're either a woman, or have never used dating apps. If you want high status grandkids, you want height for your male descendants with zero doubt."
You should check my profile. Those who are obsessed with aesthetics when picking a mate will be of little benefit to humanity's ascent.
Healthspan makes more sense. Also less resources needed for bodily upkeep at shorter height. Only technical problem may be construction of heavier infrastructure/objects.
Focusing on the height trait, amongst European nationalities the natives of the Netherlands and Montenegro are two of the tallest races and to my knowledge the Dutch attributed that mostly to dietary intake while with the Montenegrins it was attributed to the terrain.If there was a difference in primary causations would a genome comparison from individuals of both ethnicities provide evidence for that or assist in the whole process regardless?
I like the thought of a genetic comparison. That nutrition is a significant aspect of height need little more than observation—“bleeding obvious” as you said. Take the Japanese prior to the end of WWII. They were short comparatively to Americans who fought them in the Pacific theater. However, those Japanese citizens who were under 5 yo in 1945, and generations born thereafter, tower over their parents sort to speak, yet are today still not up to Americans, much less the Dutch, in average height.
I believe Warne termed this effect of environment the , “reaction range” of the genetic propensity already wired in.
Not sure exactly what you imply. If Asians eat more meat, they’d be as tall as Americans? Or, meat is an important source of protein and therefore nutrition. If the latter, then we are left with the fact that, yes, Asians don’t eat as much meat—at least beef—as Americans, but they do eat pork, chicken, and lots of fish.
In general, I’m not focusing on a particular source of nutrition, just that the Japanese as a people were better off after the war wrt how they were treated by their government under a newly established democratic system. This in turn changed their health care and nutrition and the results became obvious in a generation—way too fast to be explained by so genetic change.
"Certainly not in any way that's going to let it be one of the menu items from one of the gengineering / embryo selection startups like Orchid. Yet arguably, this is probably the highest possible value thing we could drive in humans with gengineering, and we could have been doing it a decade ago, at scale, and this is just *one* example."
Embryo selection and genetic enhancement for intelligence, integrity, and other positive human traits would be even more useful to mankind.
I completely agree those are valuable, but I think sleeplessness is still the top of the "valuable" chart.
It's literally like adding 30% to your entire conscious life (or more if GWAS-ed), and would likely have concomitant impacts on productivity, earnings, and whatever else too.
If you offered this to the broader pop, imagine everyone in your country having 30% more free time to do whatever they wanted. Imagine an entire economy growing by 15% over a few years with exactly the same population and per-worker productivity, because this time was freed up. These impacts are huge, and nothing else approaches that scale.
But yeah, if I ever get a gengineering menu I can tick boxes on, top of my list is "sleep less" then "IQ" then "high happiness set point" then "conscientiousness" then "general health" then cosmetic things.
Actually mankind needs materialism-reduction genes, more satisfied with less consumption of resources and more allocentrism genes. The constant push for satisifying female desire of a bigger nest is counterintuitive to mankind's progress for scientific breakthroughs and knowledge.
Well, considering the people (like myself) who will be early adopters of gengineering are going to be rich people, there's unfortunately precious little hope of this. They don't have problems with consumption of resources or bigger nests, they just want what's best for their kids, and rate-limiting their kids on things they have in abundance doesn't make sense.
But I urge you to advocate for opening gengineering in the politics of your own country if you feel that way, because only state-sponsored and controlled gengineering is likely to ever go this way. But in my own opinion, the more genigineering we have, of whatever flavor, the better.
And I think given that most of the problems with scientific breakthroughs and knowledge are A) academia is all about signaling and working on 90% already-thoroughly-known marginal cranks of the mill, because that's what gets you grants and citations, rather than actual innovation or progress, and B) actually smart ambitious people can go work in finance or at FAANGS for 20x academic compensation (or do their own startups for 1000x+), what we really need are thorough reforms of the academic system, including compensation, how grants are awarded, and the culture overall, if we really want to drive more scientific breakthroughs and knowledge.
But if those two factors are the biggest impediments, getting more "indepently wealthy very high IQ people" (like my kids will be) can only help on that front too.
I actually published in two science disciplines before doing startups, scientific research was my first passion. If I'd been post-economic at that time, I probably would have never left. But I wasn't, and I (accurately) calculated my impact on the world be about 1000x if I did business vs staying in academia, and now am in a place to spend money gengineering my kids. Maybe they'll decide to stay in the scientific research space, and make some marginal contribution in this area.
Hey I saw a week response by bird to your friend Uber soy could you please respond to his claims I'll quote them Uber soy I saw a response to you by Kevin Byrd can you respond to this This is some embarrassing flailing. I document several misrepresentations and inaccuracies in your video. The claims about the cause of the Flynn effect decline and the relationship of g-loaded IQ subtests and culture were just two direct refutations. You seem very confused about the fact 84% of genes are expressed somewhere in the brain at some point during development. This has no implication for racial differences unless you can specifically identify expression differences between races and their relationship to IQ. This research has not and likely cannot be done and the genetic data I presented shows there is no evidence of substantial genetic differences between races for genes associated with intelligence when you correct for biases in GWAS engage with your references the whole time, and bring up studies that address the crucial weaknesses in your cited work. It's a literature review based on some of the latest genetic studies and on economic papers that correct for the shoddy statistical analyses used in much of the IQ literature. It isn't the "sociologist's fallacy" to show that accounting for these socioeconomic differences reduces the gaps since there is strong evidence and historical documentation that these socioeconomic differences between races are not genetic themselves and again no evidence from that genetics contributes to these racial gaps. Bringing up the Coleman report is irrelevant when I present papers from this decade (not half a century ago) showing that data from 4 million students pointing toward economic inequality and segregation as driving the majority of achievement test score gap in schools. You should update your references to the proper century. Now addressing the rest of your tantrum in order: 1. Yes, correlational research is weak and needs either experimental validation or more robust methods to infer causality. 2. They are fundamentally interactions, they are not separable as genetic or environmental and they show that phenotypes can change in different environments. 3. Laughing does not refute my own published researcher showing that genes associated with intelligence do not show the patterns that would be present if natural selection were acting to make Europeans more intelligent than Africans. 4. Your evidence for dysgenics relies on faulty genetic methods prone to false-positives and from researchers with no credibility or expertise. 5. The sibling study on the Flynn is precisely the kind of well-designed study that can distinguish genetic from environmental causes and it unambiguously supports environment and precludes genetic causes. 6. Fst between dog breeds are much larger than between human populations. The paper I cited references 3-5% for human races and 27% for dogs using comparable genetic markers. 7. The distinction between within- and between group heritability is a fundamental aspect of that statistical method. Also the data I presented did show school districts where there are no racial test score gaps, a closing racial test score gap for national standardized tests, and IQ tests which show no racial gap. have to once again stress that the "g" in g-factor is not referencing genetics. genetics and the g-factor are largely unrelated thing. Also, the study about education and gender inequality is not "unknown" and uses data from three well known large studies with representative samples sizes. 9. The Ritchie and Tucker-Drob paper does not show a fade-out effect from these education gains. At least read what you try and criticize. 10. I cited papers that controlled for income and wealth and they accounted for nearly the entire gap in academic performance. 11. That paper I cited is literally the main reference in your own review paper, along with a large single-cohort study of 18,000 people showing a correlation of 0.27, which the authors settle on as the most likely value
1. Rare mutations may only have a limited role, aside from major anomalies like trisomy, mosaicism - proportional to the number of genes affected. Although the distribution of predictor weights (e.g. Figure 3 from this study https://www.nature.com/articles/s41467-019-09718-5) might suggest an extreme effect for increasingly rare variants, this is likely tempered by real-world selective pressures starting at around two standard deviations.
2. Interestingly, reaction time as shown in Figure 1 is probably the phenotype least affected by the environment and thus should demonstrate the strongest genetic influence. However, given that the observed effects were minimal, I suspect that these results, derived from the UK Biobank, might be more reflective of noise than true reality.
Thanks for the interesting and informative history of polygenic scoring.
The most frustrating thing about the current state of our genomic knowledge and capabilities is the gulf between them and what's actually available in the world. I feel like theorem and praxis have a vast gulf between them, and although we keep progressing on the theorem side, the praxis side has essentially zero serious investment or effort behind it.
Like we've been able to CRISPR single genes for soooo long now. But do you see any governments anywhere in the world doing a crash program to CRISPR the "you need 30% less sleep" SNP into their populations at large? Not at all. But just think of the productivity and economic growth potential! Governments should be falling over themselves to do this at scale for free to any citizen that wants it. As a parent, think of being able to give your kid literally 30% more conscious life, right off the bat, every day they're alive! It would be like saving 4k+ lifetimes every single year, just in the US.
And as far as I know, labs aren't GWAS-ing "sleeplessness" more generally, to do even better than that 30%. Certainly not in any way that's going to let it be one of the menu items from one of the gengineering / embryo selection startups like Orchid. Yet arguably, this is probably the highest possible value thing we could drive in humans with gengineering, and we could have been doing it a decade ago, at scale, and this is just *one* example.
> Like we've been able to CRISPR single genes for soooo long now. But do you see any governments anywhere in the world doing a crash program to CRISPR the "you need 30% less sleep" SNP into their populations at large?
What's the downside? Do we even know it?
Hint: we don't even really understand why we sleep in the first place.
> What's the downside? Do we even know it?
Not much downsides - one of my best friends has this mutation, and loooong have I envied him. And with his 3-4 hours a night, he was a competitive athlete and a high-performer at work and a founder in the non-profit domain, and much else.
I dug up a Pubmed paper on these folks once, and there basically wasn't any appreciable downsides.
And anyways, the downsides matter a lot less than the option *even being available.* I'd pay 500k to put this in some of my embryos, conservatively, and I'll happily take the downside risk. But am I able to do that, anywhere in the world? Nope. Am I able to specify "highest IQ possible," "tall and blonde and attractive," "high happiness set point," "high conscientiousness" or anything else useful that I'd be happy to pay for? Nope. We're getting to the bare minimum regions of "you can pay for a 2-5 IQ point buff," but nothing else on anything that matters.
Open up gengineering *somewhere*, anywhere in the world, and let the parents assume whatever risk profile they're comfortable with. But no, that's way too much to ask, apparently.
Meanwhile, there is zero limitation on short, sickly, dumb, ugly, unemployed, or any other maladaptive combination of traits deciding to have a kid together, which has much larger and easier to quantify risks in the child and to society, but it's totally fine. But let some parents assume the risks for gengineering? That's beyond the pale!
Sounds like you want to start an embryo editing company in Prospera!
I've legit thought of it - I'd spend a few million USD trying to get the "sleep less" SNP into a CRISPR-able state into my own embryos, so why not take on some other customers at the same time and amortize some of those costs?
I actually don't think a few mil would cut it, though, and I really don't want to do another startup right now, especially one that's going to be pretty limited in final size and upside.
But if you know of one that'll do it for about that level of investment, please do let me know. I didn't think Prospera even had a gengineering company at all? Orchid is SF, and doesn't do anything actually interesting / worth it to my mind.
"Meanwhile, there is zero limitation on short, sickly, dumb, ugly, unemployed, or any other maladaptive combination of traits deciding to have a kid together, which has much larger and easier to quantify risks in the child and to society, but it's totally fine."
I am suspicious of the meme that a person's height has any significance in the modern world. Plus, I doubt there are human genes for unemployment.
I'm assuming you're either a woman, or have never used dating apps. If you want high status grandkids, you want height for your male descendants with zero doubt.
"I'm assuming you're either a woman, or have never used dating apps. If you want high status grandkids, you want height for your male descendants with zero doubt."
You should check my profile. Those who are obsessed with aesthetics when picking a mate will be of little benefit to humanity's ascent.
Healthspan makes more sense. Also less resources needed for bodily upkeep at shorter height. Only technical problem may be construction of heavier infrastructure/objects.
Focusing on the height trait, amongst European nationalities the natives of the Netherlands and Montenegro are two of the tallest races and to my knowledge the Dutch attributed that mostly to dietary intake while with the Montenegrins it was attributed to the terrain.If there was a difference in primary causations would a genome comparison from individuals of both ethnicities provide evidence for that or assist in the whole process regardless?
I like the thought of a genetic comparison. That nutrition is a significant aspect of height need little more than observation—“bleeding obvious” as you said. Take the Japanese prior to the end of WWII. They were short comparatively to Americans who fought them in the Pacific theater. However, those Japanese citizens who were under 5 yo in 1945, and generations born thereafter, tower over their parents sort to speak, yet are today still not up to Americans, much less the Dutch, in average height.
I believe Warne termed this effect of environment the , “reaction range” of the genetic propensity already wired in.
Asians don't get to eat as much animal protein, the imported costs are higher.
Not sure exactly what you imply. If Asians eat more meat, they’d be as tall as Americans? Or, meat is an important source of protein and therefore nutrition. If the latter, then we are left with the fact that, yes, Asians don’t eat as much meat—at least beef—as Americans, but they do eat pork, chicken, and lots of fish.
In general, I’m not focusing on a particular source of nutrition, just that the Japanese as a people were better off after the war wrt how they were treated by their government under a newly established democratic system. This in turn changed their health care and nutrition and the results became obvious in a generation—way too fast to be explained by so genetic change.
And what might that reason be?As an old school cockney might have said it's bleeedin'obvious..race.
"Certainly not in any way that's going to let it be one of the menu items from one of the gengineering / embryo selection startups like Orchid. Yet arguably, this is probably the highest possible value thing we could drive in humans with gengineering, and we could have been doing it a decade ago, at scale, and this is just *one* example."
Embryo selection and genetic enhancement for intelligence, integrity, and other positive human traits would be even more useful to mankind.
I completely agree those are valuable, but I think sleeplessness is still the top of the "valuable" chart.
It's literally like adding 30% to your entire conscious life (or more if GWAS-ed), and would likely have concomitant impacts on productivity, earnings, and whatever else too.
If you offered this to the broader pop, imagine everyone in your country having 30% more free time to do whatever they wanted. Imagine an entire economy growing by 15% over a few years with exactly the same population and per-worker productivity, because this time was freed up. These impacts are huge, and nothing else approaches that scale.
But yeah, if I ever get a gengineering menu I can tick boxes on, top of my list is "sleep less" then "IQ" then "high happiness set point" then "conscientiousness" then "general health" then cosmetic things.
Actually mankind needs materialism-reduction genes, more satisfied with less consumption of resources and more allocentrism genes. The constant push for satisifying female desire of a bigger nest is counterintuitive to mankind's progress for scientific breakthroughs and knowledge.
Well, considering the people (like myself) who will be early adopters of gengineering are going to be rich people, there's unfortunately precious little hope of this. They don't have problems with consumption of resources or bigger nests, they just want what's best for their kids, and rate-limiting their kids on things they have in abundance doesn't make sense.
But I urge you to advocate for opening gengineering in the politics of your own country if you feel that way, because only state-sponsored and controlled gengineering is likely to ever go this way. But in my own opinion, the more genigineering we have, of whatever flavor, the better.
And I think given that most of the problems with scientific breakthroughs and knowledge are A) academia is all about signaling and working on 90% already-thoroughly-known marginal cranks of the mill, because that's what gets you grants and citations, rather than actual innovation or progress, and B) actually smart ambitious people can go work in finance or at FAANGS for 20x academic compensation (or do their own startups for 1000x+), what we really need are thorough reforms of the academic system, including compensation, how grants are awarded, and the culture overall, if we really want to drive more scientific breakthroughs and knowledge.
But if those two factors are the biggest impediments, getting more "indepently wealthy very high IQ people" (like my kids will be) can only help on that front too.
I actually published in two science disciplines before doing startups, scientific research was my first passion. If I'd been post-economic at that time, I probably would have never left. But I wasn't, and I (accurately) calculated my impact on the world be about 1000x if I did business vs staying in academia, and now am in a place to spend money gengineering my kids. Maybe they'll decide to stay in the scientific research space, and make some marginal contribution in this area.
Hey I saw a week response by bird to your friend Uber soy could you please respond to his claims I'll quote them Uber soy I saw a response to you by Kevin Byrd can you respond to this This is some embarrassing flailing. I document several misrepresentations and inaccuracies in your video. The claims about the cause of the Flynn effect decline and the relationship of g-loaded IQ subtests and culture were just two direct refutations. You seem very confused about the fact 84% of genes are expressed somewhere in the brain at some point during development. This has no implication for racial differences unless you can specifically identify expression differences between races and their relationship to IQ. This research has not and likely cannot be done and the genetic data I presented shows there is no evidence of substantial genetic differences between races for genes associated with intelligence when you correct for biases in GWAS engage with your references the whole time, and bring up studies that address the crucial weaknesses in your cited work. It's a literature review based on some of the latest genetic studies and on economic papers that correct for the shoddy statistical analyses used in much of the IQ literature. It isn't the "sociologist's fallacy" to show that accounting for these socioeconomic differences reduces the gaps since there is strong evidence and historical documentation that these socioeconomic differences between races are not genetic themselves and again no evidence from that genetics contributes to these racial gaps. Bringing up the Coleman report is irrelevant when I present papers from this decade (not half a century ago) showing that data from 4 million students pointing toward economic inequality and segregation as driving the majority of achievement test score gap in schools. You should update your references to the proper century. Now addressing the rest of your tantrum in order: 1. Yes, correlational research is weak and needs either experimental validation or more robust methods to infer causality. 2. They are fundamentally interactions, they are not separable as genetic or environmental and they show that phenotypes can change in different environments. 3. Laughing does not refute my own published researcher showing that genes associated with intelligence do not show the patterns that would be present if natural selection were acting to make Europeans more intelligent than Africans. 4. Your evidence for dysgenics relies on faulty genetic methods prone to false-positives and from researchers with no credibility or expertise. 5. The sibling study on the Flynn is precisely the kind of well-designed study that can distinguish genetic from environmental causes and it unambiguously supports environment and precludes genetic causes. 6. Fst between dog breeds are much larger than between human populations. The paper I cited references 3-5% for human races and 27% for dogs using comparable genetic markers. 7. The distinction between within- and between group heritability is a fundamental aspect of that statistical method. Also the data I presented did show school districts where there are no racial test score gaps, a closing racial test score gap for national standardized tests, and IQ tests which show no racial gap. have to once again stress that the "g" in g-factor is not referencing genetics. genetics and the g-factor are largely unrelated thing. Also, the study about education and gender inequality is not "unknown" and uses data from three well known large studies with representative samples sizes. 9. The Ritchie and Tucker-Drob paper does not show a fade-out effect from these education gains. At least read what you try and criticize. 10. I cited papers that controlled for income and wealth and they accounted for nearly the entire gap in academic performance. 11. That paper I cited is literally the main reference in your own review paper, along with a large single-cohort study of 18,000 people showing a correlation of 0.27, which the authors settle on as the most likely value
1. Rare mutations may only have a limited role, aside from major anomalies like trisomy, mosaicism - proportional to the number of genes affected. Although the distribution of predictor weights (e.g. Figure 3 from this study https://www.nature.com/articles/s41467-019-09718-5) might suggest an extreme effect for increasingly rare variants, this is likely tempered by real-world selective pressures starting at around two standard deviations.
2. Interestingly, reaction time as shown in Figure 1 is probably the phenotype least affected by the environment and thus should demonstrate the strongest genetic influence. However, given that the observed effects were minimal, I suspect that these results, derived from the UK Biobank, might be more reflective of noise than true reality.
2.disagree
the implication is unsound, they are not talking about shares of variance which sum to 100%.
small brain, damaged or missing short-term memory can still leave enough brain for a reaction test