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When it comes to people, you don't need much writing of DNA to get really interesting stuff. Nick Bostrom (author of Superintelligence: Paths, Dangers, Strategi

by ggreer 11y ago

When it comes to people, you don't need much writing of DNA to get really interesting stuff. Nick Bostrom (author of Superintelligence: Paths, Dangers, Strategies) has fleshed-out the idea of iterated embryo selection.[1] IES lets you do the equivalent of a millennia-long human breeding experiment in a couple of months in a lab. The result would be phenotypes that have never existed in history. These people would be smarter and healthier than anyone who lived before. It would utterly change the human condition. The key enabling technology is the ability to (in-vitro) turn embryonic stem cells into gametes. This has been done in mice, but not humans. 1. http://www.nickbostrom.com/papers/embryo.pdf http://www.nickbostrom.com/papers/embryo.pdf

frozenport 11y ago
Not clear how you translate the behavior of single cells into phenotypes, especially when that phenotype may show after many years.
- deleted 11y ago
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imaginenore 11y ago
Can't you gene edit adult yourself to become healthier and smarter?
jakobegger 11y ago
I don't think it's quite as easy. With embryo selection you are selecting genotypes, not phenotypes. The paper you link is pretty handwavy regarding that point; Bostrom seems tho think that if we just had more data we will be able to find a model that links genotypes and phenotypes. However, this is far from certain. There are too many degrees of freedom in our genome, and there are too many factors that contribute to something generic like "cognitive ability". Each individual contribution is so tiny that the effect is lost in noise, even if we sampled all humans. And even if someone comes up with a novel statistical method and finds a reasonable model, optimising that model would be pretty dangerous. If you just optimise for one trait, the chances you'll even end up with a viable embryo after a dozen iterations are pretty slim. There's a lot of selective pressure on cognitive abilities; so there must be reasons why we aren't smarter than we are. These reasons will probably kill your experimental embryo.
- deleted 11y ago
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- ggreer 11y ago
  > Each individual contribution is so tiny that the effect is lost in noise, even if we sampled all humans. Maybe for some genes, but for thousands of others, the signal is definitely there. Intelligence is highly heritable –as much as height. Just like height, it's spread across thousands of genes. Yet GWASes have found hundreds (soon to be thousands) of genes for height.[1] If researchers had a quarter of a million pairs of IQs and genomes, they'd find a similar number of genes for cognitive abilities. > If you just optimise[sic] for one trait, the chances you'll even end up with a viable embryo after a dozen iterations are pretty slim. That seems highly unlikely. We've done far worse with domesticated animals and they've been quite viable. Some breeds of dog are predisposed to genetic diseases such as hip dysplasia, but that's because we didn't have the ability to screen for genetic defects. (Or more cynically: breeders cared more about looks than diseases.) When domesticating animals, breeders often found rare traits and exaggerated them. But for human cognitive abilities, the best alleles are already prevalent in the population. It's just that nobody has lucked into all of them at once. And unlike height, there's no square-cube law to disadvantage more cognitive horsepower. > There's a lot of selective pressure on cognitive abilities; so there must be reasons why we aren't smarter than we are. These reasons will probably kill your experimental embryo. Humans have definitely been selected for intelligence, but we were also selected for other things such as famine resistance. The tradeoffs are different today, and we can do a much better job than nature. We can fix a lot of mutation load. Really, we're not nearly as smart as we could be. In the words of Nick Bostrom: > Far from being the smartest possible biological species, we are probably better thought of as the stupidest possible biological species capable of starting a technological civilization—a niche we filled because we got there first, not because we are in any sense optimally adapted to it. 1. http://www.nature.com/ng/journal/v46/n11/full/ng.3097.html http://www.nature.com/ng/journal/v46/n11/full/ng.3097.html
  - jakobegger 11y ago
    The correlations seen in the the genome-wide-association study are impressive, but I don't see how they would help in this case. If you'd use that data for a model, you'd end up with a model that has thousands of parameters, and each of them has a huge margin of error. Using this data, how precise would your model be? Ie. given a genome, how precisely could you estimate height? Concerning your comparison with breeding: you seem to misunderstand me. I don't think that breeding per se doesn't work. Breeding by looking at phenotypes works wonderful. But what you suggest is to just iterate to optimise [according to my spellchecker that is how you spell it] according to a model. You are missing the step where those embryos grow (or fail to grow) into adults. Without this step, your optimisation procedure will drift randomly on every axis that your model doesn't measure.
kanzure 11y ago
Why would you need an embryo to select a genotype? You don't need to physically embody genomes in embryos just to get iterative selection.... you can do that informatically before you get to the stage of somatic cell nuclear transfer to inject DNA/genome into the cell. Anders should aspire more towards George Church and less towards Nick Bostrom. (I know he wasn't on the paper, but whatever. It's been on my mind.) While I am at it: here's some (typical disclaimer applies) notes on open-source DNA synthesis machine design: http://diyhpl.us/wiki/dna/synthesis/notes/ http://diyhpl.us/wiki/dna/synthesis/notes/ Re: Genotype/phenotype; once we find stable phenotypes, we should make more reliable structures on top of those phenotypes, instead of messing with the genetics. For example, for protein-based molecular nanotechnology, nobody really wants to spend their time doing a trillion different folds in simulation or in the lab just to find their target structure. Instead you will have to skip tweaking genotypes (because of the large costs of exploring the genetic landscape (really, take whatever you can get)) and just use lego brick phenotypes... at least for nano/molecular structures (nanotech). Other changes require exploration of evolutionary/genetic landscape, until heuristics get better if ever, which will continue to be expensive even with $1/genome synthesis costs.
- fisk 11y ago
  Stable/lego-brick phenotypes: Is this about coming up with something akin to 0 and 1 and then building from the ground up? Or is this about something that's closer to familiar biology but with some fiendishly clever compartmentalization somehow?
  - kanzure 11y ago
    Well, given our tremendous struggle with rational design of novel protein nanostructures, my point was that we should avoid that difficulty by designing some ligand-binding proteins only once, then assemble those into the larger structures that we desire. Of course, knowing all protein (structural) phenotypes for all amino acid sequences up to length=100 would also be nice... but seems unlikely something we can work towards due to constraints of scarce universe.
Gatsky 11y ago
This strikes me as an extremely bad idea. Putting aside all the issues about whether it is even possible to select genetic traits that will predictably result in higher 'intelligence', how do you even define this outcome? You can only optimise what you can measure, and it seems that this process will just produce people that are good at intelligence tests. At what cost to all other aspects and dimensions of human experience and achievement? How do you prove that this is a good idea for a particular individual? My opinion: Bostrom has some interesting perspectives, but has always tended to preach pseudoscience to an audience that is entirely non-critical.

by ggreer 11y ago

frozenport 11y ago

Not clear how you translate the behavior of single cells into phenotypes, especially when that phenotype may show after many years.

deleted 11y ago
[deleted]

imaginenore 11y ago

Can't you gene edit adult yourself to become healthier and smarter?

jakobegger 11y ago

I don't think it's quite as easy. With embryo selection you are selecting genotypes, not phenotypes. The paper you link is pretty handwavy regarding that point; Bostrom seems tho think that if we just had more data we will be able to find a model that links genotypes and phenotypes. However, this is far from certain. There are too many degrees of freedom in our genome, and there are too many factors that contribute to something generic like "cognitive ability". Each individual contribution is so tiny that the effect is lost in noise, even if we sampled all humans. And even if someone comes up with a novel statistical method and finds a reasonable model, optimising that model would be pretty dangerous. If you just optimise for one trait, the chances you'll even end up with a viable embryo after a dozen iterations are pretty slim. There's a lot of selective pressure on cognitive abilities; so there must be reasons why we aren't smarter than we are. These reasons will probably kill your experimental embryo.

deleted 11y ago
[deleted]
ggreer 11y ago
> Each individual contribution is so tiny that the effect is lost in noise, even if we sampled all humans. Maybe for some genes, but for thousands of others, the signal is definitely there. Intelligence is highly heritable –as much as height. Just like height, it's spread across thousands of genes. Yet GWASes have found hundreds (soon to be thousands) of genes for height.[1] If researchers had a quarter of a million pairs of IQs and genomes, they'd find a similar number of genes for cognitive abilities. > If you just optimise[sic] for one trait, the chances you'll even end up with a viable embryo after a dozen iterations are pretty slim. That seems highly unlikely. We've done far worse with domesticated animals and they've been quite viable. Some breeds of dog are predisposed to genetic diseases such as hip dysplasia, but that's because we didn't have the ability to screen for genetic defects. (Or more cynically: breeders cared more about looks than diseases.) When domesticating animals, breeders often found rare traits and exaggerated them. But for human cognitive abilities, the best alleles are already prevalent in the population. It's just that nobody has lucked into all of them at once. And unlike height, there's no square-cube law to disadvantage more cognitive horsepower. > There's a lot of selective pressure on cognitive abilities; so there must be reasons why we aren't smarter than we are. These reasons will probably kill your experimental embryo. Humans have definitely been selected for intelligence, but we were also selected for other things such as famine resistance. The tradeoffs are different today, and we can do a much better job than nature. We can fix a lot of mutation load. Really, we're not nearly as smart as we could be. In the words of Nick Bostrom: > Far from being the smartest possible biological species, we are probably better thought of as the stupidest possible biological species capable of starting a technological civilization—a niche we filled because we got there first, not because we are in any sense optimally adapted to it. 1. http://www.nature.com/ng/journal/v46/n11/full/ng.3097.html http://www.nature.com/ng/journal/v46/n11/full/ng.3097.html
- jakobegger 11y ago
  The correlations seen in the the genome-wide-association study are impressive, but I don't see how they would help in this case. If you'd use that data for a model, you'd end up with a model that has thousands of parameters, and each of them has a huge margin of error. Using this data, how precise would your model be? Ie. given a genome, how precisely could you estimate height? Concerning your comparison with breeding: you seem to misunderstand me. I don't think that breeding per se doesn't work. Breeding by looking at phenotypes works wonderful. But what you suggest is to just iterate to optimise [according to my spellchecker that is how you spell it] according to a model. You are missing the step where those embryos grow (or fail to grow) into adults. Without this step, your optimisation procedure will drift randomly on every axis that your model doesn't measure.

kanzure 11y ago

Why would you need an embryo to select a genotype? You don't need to physically embody genomes in embryos just to get iterative selection.... you can do that informatically before you get to the stage of somatic cell nuclear transfer to inject DNA/genome into the cell. Anders should aspire more towards George Church and less towards Nick Bostrom. (I know he wasn't on the paper, but whatever. It's been on my mind.) While I am at it: here's some (typical disclaimer applies) notes on open-source DNA synthesis machine design: http://diyhpl.us/wiki/dna/synthesis/notes/ http://diyhpl.us/wiki/dna/synthesis/notes/ Re: Genotype/phenotype; once we find stable phenotypes, we should make more reliable structures on top of those phenotypes, instead of messing with the genetics. For example, for protein-based molecular nanotechnology, nobody really wants to spend their time doing a trillion different folds in simulation or in the lab just to find their target structure. Instead you will have to skip tweaking genotypes (because of the large costs of exploring the genetic landscape (really, take whatever you can get)) and just use lego brick phenotypes... at least for nano/molecular structures (nanotech). Other changes require exploration of evolutionary/genetic landscape, until heuristics get better if ever, which will continue to be expensive even with $1/genome synthesis costs.

fisk 11y ago
Stable/lego-brick phenotypes: Is this about coming up with something akin to 0 and 1 and then building from the ground up? Or is this about something that's closer to familiar biology but with some fiendishly clever compartmentalization somehow?
- kanzure 11y ago
  Well, given our tremendous struggle with rational design of novel protein nanostructures, my point was that we should avoid that difficulty by designing some ligand-binding proteins only once, then assemble those into the larger structures that we desire. Of course, knowing all protein (structural) phenotypes for all amino acid sequences up to length=100 would also be nice... but seems unlikely something we can work towards due to constraints of scarce universe.

Gatsky 11y ago

This strikes me as an extremely bad idea. Putting aside all the issues about whether it is even possible to select genetic traits that will predictably result in higher 'intelligence', how do you even define this outcome? You can only optimise what you can measure, and it seems that this process will just produce people that are good at intelligence tests. At what cost to all other aspects and dimensions of human experience and achievement? How do you prove that this is a good idea for a particular individual? My opinion: Bostrom has some interesting perspectives, but has always tended to preach pseudoscience to an audience that is entirely non-critical.