23 ms·

Scientists say they can read nearly the whole genome of an IVF-created embryo

81 points by Metacelsus 5y ago

deleted 5y ago
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exdsq 5y ago
What’s the choke point of scanning an entire genome? Is it purely computational? Imaging? Biological unknowns?
- jkingsman 5y ago
  For IVF embryos, it's the small amount of genetic material which makes accurate sequencing difficult. For standard human whole genome sequencing (WGS), the fastest times are down to five hours[1] (although that is exceptional), for which the imaging was massively parallelized and it seems that the choke point was computational for that particular case (sequencing like this basically multiples the DNA, shreds all the copies, images each shred in a reasonably-parallel manner, and then uses longest-common-subsequence to put all the shreds back together digitally). Average WGS times for something a person can buy for a couple hundred dollars take a few weeks, and will usually be bottlenecked by logistics (mailing things, getting it to the lab, etc.) and then the imaging (a flow cell runs the fragments over an imaging device; parallelization is accomplished by running multiple flow cells at once). I might be slightly off on my terminology here but the idea is broadly correct, I think: Differing grades of sequencing are determined by the average depth of fragments for each base-pair -- e.g. 1x sequencing implies an average coverage of one fragment per base-pair, which could lead to mis-aligned or improperly joined samples. 30x-50x sequencing is pretty common for consumer grade WGS these days, which gives a higher number of fragments that allows you to weed out bad reads or incorrect joins of the sequence, though errors can still occur. This is usually sufficient for diploid (having two values for each base pair, one maternal and one paternal) humans, since it's important to determine if the basepair is heterozygous (different bases from each parent) or homozygous (same base from each parent). However, if you're doing cancer sequencing, a tumor may contain many many more different genes, so a massively deeper sequencing depth is required to ensure you have reasonable statistical certainty on what variations occur within the different genomes. Higher depth == more material == longer time to sequence since you have more material to image. Note that services like 23andMe are NOT doing whole genome sequencing; they are using specialized flow cells that only examine certain specific sites on the genome called single nucleotide polymorphisms[2], which are traits or indicators that are turned on or off by a single nucleotide, hence it being much cheaper and faster to run. [1]: https://med.stanford.edu/news/all-news/2022/01/dna-sequencing-technique.html#:~:text=A%20research%20effort%20led%20by,5%20hours%20and%202%20minutes https://med.stanford.edu/news/all-news/2022/01/dna-sequencin.... [2]: https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism
  - exdsq 5y ago
    Thanks for your response! So is it true to say every genome could be sequenced, assuming time and money isn’t an issue?
    - timy2shoes 5y ago
      Starting material is a huge problem. You need at least 50ng of DNA for an Illumina sequencing run, usually more if you want to sequence ultra deep, which you will need for whole genome sequencing. For PCR you need at least 0.1ng (usually higher) of DNA. But a single cell has about 80 pg of DNA. So you need to amplify the DNA several orders of magnitude before you can apply standard PCR. Several approaches can solve this problem, DOP-PCR, MDA, MALBAC. But each results in biased amplification, with differing biases with each method. Source: I worked on the computational modeling of this problem in grad school, https://academic.oup.com/bioinformatics/article/30/22/3159/2391301 https://academic.oup.com/bioinformatics/article/30/22/3159/2...
      - tux1968 5y ago
        The most interesting idea from the article, that was new to me, was using larger samples available from each parent, to augment and guide the analysis of the small amount of material available from the embryo. Obvious idea after you hear it, but very clever nonetheless.
    - dekhn 5y ago
      if you're asking whether we could sequence 7 billion people, yes, it would be absolutely possible. Obtaining samples would be harder than the sequencing. If you really took this seriously there would be only 3 sequencing sites in the world and they would be located close to the largest datacenters. Each sequence is about 100G data (the raw data file that's shipped around) so if you really wanted to keep all of that it's 700 exabytes, but since you're sequencing everybody, you can instead create a tree structure of deltas from references with additional nodes representing major haplotypes and other structure. This would be more like ~1M-1G/person, so 7 petabytes to 7 exabytes, well within the storage limits of a modern datacenter cluster. To go along with that storage, you'd also need ~1M fast CPUs and ~250K fast GPUs, plenty of RAM, and a really good privacy and security story. All of that could be formatted for large-scale analytics and the problem treated much like machine learning/data science problems in ads and other similar areas. If you're really serious, this is just a bulk buy for one of the data center providers and they would be happy to make a fixed profit margin contract to do this for you. I helped set up all the infrastructure to enable google to do this ~10 years ago (I got a patent on compressing DNA for storage) and now they're at the point of hosting this sort of service (terra bio). I could do everything I described above for $25B but there is absolutely no medical reason to do anything of this scale.
- arrosenberg 5y ago
  It's very doable, but we only know what a small amount of the genome is actually doing. Whole Exome testing hits the majority of the points people are interested in and is way less computationally expensive, since it's a fraction of the genome.
  - exdsq 5y ago
    Okay interesting - so reading the genome is basically solved nowadays and it's understanding what it's actually doing where we're working atm?
throw0101a 5y ago
Gattaca here we come! \o/ * https://en.wikipedia.org/wiki/Gattaca https://en.wikipedia.org/wiki/Gattaca :)
- monkeybutton 5y ago
  Onwards to the Eugenics Wars and then the post scarcity Startrek future!
- whatshisface 5y ago
  Directly testing people's IQ through say contrived interview questions (ever wondered why people care about leetcode[0]?) will always be more accurate than predicting it from their DNA. It is difficult to say how much of IQ is genetic, but estimates range from 50% to 80%, placing an upper bound on the effectiveness of the exact technique they used in GATTACA. (But, I want to emphasize, the more accurate way of doing it is already being done.) [0] One objection to calling leetcode an IQ test would be that some people "grind leetcode," as in, practice at it to get better, but did you know that Raven's progressive matrices has a large practice effect? In fact, I might raise your score just by telling you that a lot of the questions are based around XORing the presence of symbols in the pictures. If companies were giving culture-free IQ tests rather than leetcode ones we'd see the exact same pre-interview behaviors, including practicing tasks that don't resemble the job being interviewed for. [1] https://en.wikipedia.org/wiki/Heritability_of_IQ#Estimates https://en.wikipedia.org/wiki/Heritability_of_IQ#Estimates
- deleted 5y ago
  [deleted]
Flatcircle 5y ago
Expecting a contrarian article in 10 to 15 years that says the IVF genome analysis is imperfect and parents have been making incorrect decisions on flawed data.
- whatshisface 5y ago
  It only has to be better than random, right?
  - jacquesm 5y ago
    Indeed. And it could be worse.
  - TOMDM 5y ago
    Not necessarily, if the confidence of the prediction doesn't match the real odds of outcome. Parents may make special accommodations for the needs of children with genetic difficulties that they otherwise wouldn't based on their confidence in genetic screening.
- areoform 5y ago
  The error rate for sequencing is significant and can easily lead to incorrect assumptions + decisions, > The average error rate determined was 0.24 ± 0.06% per base and the percentage of mutated sequences was found to be 6.4 ± 1.24%. https://www.nature.com/articles/s41598-018-29325-6 https://www.nature.com/articles/s41598-018-29325-6
  - topynate 5y ago
    Won't matter for highly polygenic traits. For monogenetic disorders like Tay-Sachs, it will provide another line of defence along with conventional pre-implantation screening and pre-natal screening.
    - TOMDM 5y ago
      I think what people are worried about is that parents may neglect to take measures they otherwise would based on overconfidence in genetic screening.
legalcorrection 5y ago
Thinking about the social and political implications of this in the long run. Any society or segment of any society that isn't producing average 120 IQ babies with superior sensory perception, physical strength, dexterity, and so forth, is going to turn itself into a permanent human underclass. Eugenics is here to stay this time.
- evan_ 5y ago
  > Any society or segment of any society that isn't producing average 120 IQ babies with superior sensory perception, physical strength, dexterity, and so forth Where all the women are strong, all the men are good-looking, and all the children are above average.
  - sweetbitter 5y ago
    Haha, Lake Wobegon?
- unsupp0rted 5y ago
  That particular underclass problem seems unlikely, relative to how much any 120 IQ human pales in comparison to any synthetic AGI or even domain-expert AI. The real underclass would be humans vs. machines, which would 10x, 100x or 1000x IQ, perception, strength, dexterity... pretty much any measure. By the time we can make 120 IQ humans consistently, we'll be able to make 120 IQ machines consistently. And a couple years or perhaps hours after that the 120 IQ machines will be able to make 240 IQ machines and so on.
- ajconway 5y ago
  The world is massively unfair as it is. Would anyone even notice already "privileged" societies becoming a little bit more privileged? Who knows, maybe our IQ 120 overlords will be kind to make the tech available for everyone else.
  - legalcorrection 5y ago
    A 120 average IQ population would run circles around a 100 average IQ population, even starting from a much lower position. Of course, there's still the question of whether society is organized such that people of exceptional talent rise to power, and whether they have the incentive to do great things. My main concern isn't the tech being inaccessible to poorer people or countries. International intellectual property protection has always been precarious, and I guarantee that e.g. India won't just accept having a dumber population because "oh well, an American company owns the patents and we can't afford mass licensing." Rather, Western societies have strong anti-eugenic impulses because of 1) the Christian legacy, 2) the popular fixation on WW2 atrocities, and 3) a political taboo against acknowledging population-level differences in mental (and to a lesser extent, even physical) attributes. I could see China being much more willing to embrace eugenic technology on a shorter timescale than the United States. And that could be the death blow to the US.
015UUZn8aEvW 5y ago
Embryo selection based on genome sequencing is already being done: https://astralcodexten.substack.com/p/welcome-polygenically-screened-babies?s=r https://astralcodexten.substack.com/p/welcome-polygenically-...
- dekhn 5y ago
  Your example is "genetic" testing- it only samples a limited number of locations in the genome. This method is more like whole genome sequencing.
  - abcc8 5y ago
    There really aren't that many reasons to sequence the entire genome in this context. Specific disease causing mutations in the parents can be specifically targeted in the embryo/fetus. Similarly, PRS scores don't require full genome sequencing to generate (but also aren't ready for prime time routine usage). Also, aneuploidy detection doesn't require genome sequencing. This is just a few examples.
    - dekhn 5y ago
      I was just pedantically correcting the person I was replying to.
- Metacelsus 5y ago
  This method is similar, but uses the parents' genomic data to improve predictions of the embryo's genome (since sequencing only a few cells gives low-quality data).
belval 5y ago
I see a lot of comments underscoring the possible eugenics implication of this, but I am curious as to why everyone always paints it as a negative? Even in our very diversity-conscious institutions we can generally agree that some things are plain bad. You don't want a blind or deaf child. You don't want one with down syndrome or deformities that would just make their life difficult. I wonder if the high level of opposition to this does not come from us being naturally scared of becoming irrelevant. A society capable of producing disease-less 120 IQ adults would progress faster. Yes there are a ton of ethical concerns about building a society where hierarchical boundaries find their justification in science, but I see these arguments as myopic. Inequalities have always existed, the only difference is that now nobody would have genetic diseases.
- whatshisface 5y ago
  >now nobody would have genetic diseases. Nobody with parents who can afford IVF would have genetic diseases. Nobody would rise from an ignoble birth to greatness ever again... or at least not in countries without universal healthcare.
  - thegrimmest 5y ago
    Doesn't that just mean that the bar for "greatness" will have risen? Isn't that a net gain?
    - whatshisface 5y ago
      The real world is a mixture of zero-sum and positive-sum games, and people do not like the idea that they and their descendants will be destined to lose (in a compounding way) every competition. After a few generations of selection you will have a large population of people who wouldn't be good starting points even if they could afford it, because their genomes would be far behind by that point. Unless you want that you happen, you'd better make sure that everybody gets it if anybody does.
  - belval 5y ago
    Equality is great, but the situation would be no different than someone having access to healthcare/higher education/equal opportunities. After a few decades that technology would become commoditized just like everything else. It's not as if it was impossible to enforce regulations around that sort of thing.
Gatsky 5y ago
Impressive study, kudos to the bioinformaticians who did this! This could be an option for parents with a genetic condition who don’t want to pass it on. In terms of gattaca style super people (which I find quite repugnant) the recombination events are still random at the end of the day, so you’d have to screen quite a few embryos and there would be trade-offs. If you were really serious about it, the process would start with selecting partners based on their genetic fitness, and also using young fathers.
- bradleyjg 5y ago
  This could be an option for parents with a genetic condition who don’t want to pass it on. Most of the genetic disorders we know about can already be screened for (those that involve a single gene). This opens the door for polygenic screening but the underlying patterns to screen for are, in most cases, only weakly understood. We’d need to do a lot more research on adults with these diseases to get to the point where we can select against them in embryos. On top of that the amount of selection we can do is limited by the number of embryos to choose between. In many cases that’s a very small number.
  - Gatsky 5y ago
    There are quite a lot of less severe conditions which aren’t easily testable on an embryo. That was the motivation for the research as I understand it. The whole polygenic thing isn’t very compelling, I agree.
    - bradleyjg 5y ago
      My understanding is monogenomic testing has gotten very extensive as well as less expensive and faster. It’s gotten to the point where if you can get genetic samples from the parents and all grandparents the only limitation is knowing what to look for.
  - oneoff786 5y ago
    I’m starting to look into this. We have a single uncommon mutation to deal with, that’s just a fairly large cancer risk. Early advice has been that it’s still pretty hard to do single gene mutation screens. Needing samples from multiple relatives with the mutation to build a reliable screen.
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programmertote 5y ago
Coincidentally, I have a friend who is in the second cycle of this IVF procedure to select an embryo that does not carry the genes associated with polycystic kidney disease (PKD). When I heard it last week for the first time, I thought it is already an established procedure. Here, I'm learning that it is a relatively cutting-edge approach and I am now looking forward to asking my friend more about this next time we meet.
- llebttam 5y ago
  Commercial products in the space have been around for several years but can only screen for a small number of genetic diseases at a time. For example, Natera's Spectrum screens for chromosomal abnormalities (eg Down Syndrome) plus one custom genetic problem for a single condition of greatest concern. https://www.natera.com/womens-health/spectrum-preimplantation-genetics/ https://www.natera.com/womens-health/spectrum-preimplantatio... Some polygenic screening services that look at a much larger number of conditions are just reaching market now (eg Orchid Health), though our ability to map genes correlated with polygenic traits to phenotype results is still in its early stages. https://www.orchidhealth.com/ https://www.orchidhealth.com/
WheelsAtLarge 5y ago
Anyone know of any unexpected consequences of using this for IVF? It seems to me that we are falling into brave-new-world territory without really trying. I'm sure parents will do this to help their kids but I wonder what the negative issues will be? Gender selection is one but that's already being done by other means. What will this particular technology bring?
- musicale 5y ago
  The Gattaca premise sounds pretty logical but not unexpected. Presumably they will optimize for what they might view to be "favorable" genes associated with preferred traits (skin/hair/eye color, beauty/symmetry, strength, height, intelligence, disease resistance, aggression, etc.) while attempting to eliminate the others. This will (possibly) convey an increased "genetic" advantage upon the wealthy and privileged, while reinforcing societal structures that punish and exploit those who haven't been engineered the same way.
  - WheelsAtLarge 5y ago
    Good point, people don't realize it or admit it but being born with what society defines as beautiful features gives a person big advantages in life. It's like hitting the lottery as far as advantages vs someone that's not. If you're already wealthy you'll be able to buy those advantages for your kids. It will be one of the greatest inheritance parents can give them.
  - 0ldskool 5y ago
    Well the governments job is to create laws to make it easier for humans to live together. Even if Gattaca style gene selection is available, laws can be put into place to prevent discrimination. I.e. it is 100% illegal to do genetic testing for anyone other then yourself or your under-aged children. Those tests can only be done by a doctor and cannot be transferred or shared with anyone other than another doctor. Any employer or person that attempts to do a genetic test on someone can face jail-time.
- ravi-delia 5y ago
  Check out Gwern's analysis(https://www.gwern.net/Embryo-selection https://www.gwern.net/Embryo-selection) of this kind of technology. It suggests a somewhat noticeable effect, but not a particularly large or worthwhile one. That doesn't factor in new technology, but the methodology is all there so it shouldn't be too hard to plug in the new values. I haven't done that yet, but I'd be surprised if there was a big shift.
flobosg 5y ago
The actual paper: https://www.nature.com/articles/s41591-022-01735-0 https://www.nature.com/articles/s41591-022-01735-0

81 points by Metacelsus 5y ago

deleted 5y ago

[deleted]

exdsq 5y ago

What’s the choke point of scanning an entire genome? Is it purely computational? Imaging? Biological unknowns?

jkingsman 5y ago
For IVF embryos, it's the small amount of genetic material which makes accurate sequencing difficult. For standard human whole genome sequencing (WGS), the fastest times are down to five hours[1] (although that is exceptional), for which the imaging was massively parallelized and it seems that the choke point was computational for that particular case (sequencing like this basically multiples the DNA, shreds all the copies, images each shred in a reasonably-parallel manner, and then uses longest-common-subsequence to put all the shreds back together digitally). Average WGS times for something a person can buy for a couple hundred dollars take a few weeks, and will usually be bottlenecked by logistics (mailing things, getting it to the lab, etc.) and then the imaging (a flow cell runs the fragments over an imaging device; parallelization is accomplished by running multiple flow cells at once). I might be slightly off on my terminology here but the idea is broadly correct, I think: Differing grades of sequencing are determined by the average depth of fragments for each base-pair -- e.g. 1x sequencing implies an average coverage of one fragment per base-pair, which could lead to mis-aligned or improperly joined samples. 30x-50x sequencing is pretty common for consumer grade WGS these days, which gives a higher number of fragments that allows you to weed out bad reads or incorrect joins of the sequence, though errors can still occur. This is usually sufficient for diploid (having two values for each base pair, one maternal and one paternal) humans, since it's important to determine if the basepair is heterozygous (different bases from each parent) or homozygous (same base from each parent). However, if you're doing cancer sequencing, a tumor may contain many many more different genes, so a massively deeper sequencing depth is required to ensure you have reasonable statistical certainty on what variations occur within the different genomes. Higher depth == more material == longer time to sequence since you have more material to image. Note that services like 23andMe are NOT doing whole genome sequencing; they are using specialized flow cells that only examine certain specific sites on the genome called single nucleotide polymorphisms[2], which are traits or indicators that are turned on or off by a single nucleotide, hence it being much cheaper and faster to run. [1]: https://med.stanford.edu/news/all-news/2022/01/dna-sequencing-technique.html#:~:text=A%20research%20effort%20led%20by,5%20hours%20and%202%20minutes https://med.stanford.edu/news/all-news/2022/01/dna-sequencin.... [2]: https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism
- exdsq 5y ago
  Thanks for your response! So is it true to say every genome could be sequenced, assuming time and money isn’t an issue?
  - timy2shoes 5y ago
    Starting material is a huge problem. You need at least 50ng of DNA for an Illumina sequencing run, usually more if you want to sequence ultra deep, which you will need for whole genome sequencing. For PCR you need at least 0.1ng (usually higher) of DNA. But a single cell has about 80 pg of DNA. So you need to amplify the DNA several orders of magnitude before you can apply standard PCR. Several approaches can solve this problem, DOP-PCR, MDA, MALBAC. But each results in biased amplification, with differing biases with each method. Source: I worked on the computational modeling of this problem in grad school, https://academic.oup.com/bioinformatics/article/30/22/3159/2391301 https://academic.oup.com/bioinformatics/article/30/22/3159/2...
    - tux1968 5y ago
      The most interesting idea from the article, that was new to me, was using larger samples available from each parent, to augment and guide the analysis of the small amount of material available from the embryo. Obvious idea after you hear it, but very clever nonetheless.
  - dekhn 5y ago
    if you're asking whether we could sequence 7 billion people, yes, it would be absolutely possible. Obtaining samples would be harder than the sequencing. If you really took this seriously there would be only 3 sequencing sites in the world and they would be located close to the largest datacenters. Each sequence is about 100G data (the raw data file that's shipped around) so if you really wanted to keep all of that it's 700 exabytes, but since you're sequencing everybody, you can instead create a tree structure of deltas from references with additional nodes representing major haplotypes and other structure. This would be more like ~1M-1G/person, so 7 petabytes to 7 exabytes, well within the storage limits of a modern datacenter cluster. To go along with that storage, you'd also need ~1M fast CPUs and ~250K fast GPUs, plenty of RAM, and a really good privacy and security story. All of that could be formatted for large-scale analytics and the problem treated much like machine learning/data science problems in ads and other similar areas. If you're really serious, this is just a bulk buy for one of the data center providers and they would be happy to make a fixed profit margin contract to do this for you. I helped set up all the infrastructure to enable google to do this ~10 years ago (I got a patent on compressing DNA for storage) and now they're at the point of hosting this sort of service (terra bio). I could do everything I described above for $25B but there is absolutely no medical reason to do anything of this scale.
arrosenberg 5y ago
It's very doable, but we only know what a small amount of the genome is actually doing. Whole Exome testing hits the majority of the points people are interested in and is way less computationally expensive, since it's a fraction of the genome.
- exdsq 5y ago
  Okay interesting - so reading the genome is basically solved nowadays and it's understanding what it's actually doing where we're working atm?

throw0101a 5y ago

Gattaca here we come! \o/ * https://en.wikipedia.org/wiki/Gattaca https://en.wikipedia.org/wiki/Gattaca :)

monkeybutton 5y ago
Onwards to the Eugenics Wars and then the post scarcity Startrek future!
whatshisface 5y ago
Directly testing people's IQ through say contrived interview questions (ever wondered why people care about leetcode[0]?) will always be more accurate than predicting it from their DNA. It is difficult to say how much of IQ is genetic, but estimates range from 50% to 80%, placing an upper bound on the effectiveness of the exact technique they used in GATTACA. (But, I want to emphasize, the more accurate way of doing it is already being done.) [0] One objection to calling leetcode an IQ test would be that some people "grind leetcode," as in, practice at it to get better, but did you know that Raven's progressive matrices has a large practice effect? In fact, I might raise your score just by telling you that a lot of the questions are based around XORing the presence of symbols in the pictures. If companies were giving culture-free IQ tests rather than leetcode ones we'd see the exact same pre-interview behaviors, including practicing tasks that don't resemble the job being interviewed for. [1] https://en.wikipedia.org/wiki/Heritability_of_IQ#Estimates https://en.wikipedia.org/wiki/Heritability_of_IQ#Estimates
deleted 5y ago
[deleted]

Flatcircle 5y ago

Expecting a contrarian article in 10 to 15 years that says the IVF genome analysis is imperfect and parents have been making incorrect decisions on flawed data.

whatshisface 5y ago
It only has to be better than random, right?
- jacquesm 5y ago
  Indeed. And it could be worse.
- TOMDM 5y ago
  Not necessarily, if the confidence of the prediction doesn't match the real odds of outcome. Parents may make special accommodations for the needs of children with genetic difficulties that they otherwise wouldn't based on their confidence in genetic screening.
areoform 5y ago
The error rate for sequencing is significant and can easily lead to incorrect assumptions + decisions, > The average error rate determined was 0.24 ± 0.06% per base and the percentage of mutated sequences was found to be 6.4 ± 1.24%. https://www.nature.com/articles/s41598-018-29325-6 https://www.nature.com/articles/s41598-018-29325-6
- topynate 5y ago
  Won't matter for highly polygenic traits. For monogenetic disorders like Tay-Sachs, it will provide another line of defence along with conventional pre-implantation screening and pre-natal screening.
  - TOMDM 5y ago
    I think what people are worried about is that parents may neglect to take measures they otherwise would based on overconfidence in genetic screening.

legalcorrection 5y ago

Thinking about the social and political implications of this in the long run. Any society or segment of any society that isn't producing average 120 IQ babies with superior sensory perception, physical strength, dexterity, and so forth, is going to turn itself into a permanent human underclass. Eugenics is here to stay this time.

evan_ 5y ago
> Any society or segment of any society that isn't producing average 120 IQ babies with superior sensory perception, physical strength, dexterity, and so forth Where all the women are strong, all the men are good-looking, and all the children are above average.
- sweetbitter 5y ago
  Haha, Lake Wobegon?
unsupp0rted 5y ago
That particular underclass problem seems unlikely, relative to how much any 120 IQ human pales in comparison to any synthetic AGI or even domain-expert AI. The real underclass would be humans vs. machines, which would 10x, 100x or 1000x IQ, perception, strength, dexterity... pretty much any measure. By the time we can make 120 IQ humans consistently, we'll be able to make 120 IQ machines consistently. And a couple years or perhaps hours after that the 120 IQ machines will be able to make 240 IQ machines and so on.
ajconway 5y ago
The world is massively unfair as it is. Would anyone even notice already "privileged" societies becoming a little bit more privileged? Who knows, maybe our IQ 120 overlords will be kind to make the tech available for everyone else.
- legalcorrection 5y ago
  A 120 average IQ population would run circles around a 100 average IQ population, even starting from a much lower position. Of course, there's still the question of whether society is organized such that people of exceptional talent rise to power, and whether they have the incentive to do great things. My main concern isn't the tech being inaccessible to poorer people or countries. International intellectual property protection has always been precarious, and I guarantee that e.g. India won't just accept having a dumber population because "oh well, an American company owns the patents and we can't afford mass licensing." Rather, Western societies have strong anti-eugenic impulses because of 1) the Christian legacy, 2) the popular fixation on WW2 atrocities, and 3) a political taboo against acknowledging population-level differences in mental (and to a lesser extent, even physical) attributes. I could see China being much more willing to embrace eugenic technology on a shorter timescale than the United States. And that could be the death blow to the US.

015UUZn8aEvW 5y ago

Embryo selection based on genome sequencing is already being done: https://astralcodexten.substack.com/p/welcome-polygenically-screened-babies?s=r https://astralcodexten.substack.com/p/welcome-polygenically-...

dekhn 5y ago
Your example is "genetic" testing- it only samples a limited number of locations in the genome. This method is more like whole genome sequencing.
- abcc8 5y ago
  There really aren't that many reasons to sequence the entire genome in this context. Specific disease causing mutations in the parents can be specifically targeted in the embryo/fetus. Similarly, PRS scores don't require full genome sequencing to generate (but also aren't ready for prime time routine usage). Also, aneuploidy detection doesn't require genome sequencing. This is just a few examples.
  - dekhn 5y ago
    I was just pedantically correcting the person I was replying to.
Metacelsus 5y ago
This method is similar, but uses the parents' genomic data to improve predictions of the embryo's genome (since sequencing only a few cells gives low-quality data).

belval 5y ago

I see a lot of comments underscoring the possible eugenics implication of this, but I am curious as to why everyone always paints it as a negative? Even in our very diversity-conscious institutions we can generally agree that some things are plain bad. You don't want a blind or deaf child. You don't want one with down syndrome or deformities that would just make their life difficult. I wonder if the high level of opposition to this does not come from us being naturally scared of becoming irrelevant. A society capable of producing disease-less 120 IQ adults would progress faster. Yes there are a ton of ethical concerns about building a society where hierarchical boundaries find their justification in science, but I see these arguments as myopic. Inequalities have always existed, the only difference is that now nobody would have genetic diseases.

whatshisface 5y ago
>now nobody would have genetic diseases. Nobody with parents who can afford IVF would have genetic diseases. Nobody would rise from an ignoble birth to greatness ever again... or at least not in countries without universal healthcare.
- thegrimmest 5y ago
  Doesn't that just mean that the bar for "greatness" will have risen? Isn't that a net gain?
  - whatshisface 5y ago
    The real world is a mixture of zero-sum and positive-sum games, and people do not like the idea that they and their descendants will be destined to lose (in a compounding way) every competition. After a few generations of selection you will have a large population of people who wouldn't be good starting points even if they could afford it, because their genomes would be far behind by that point. Unless you want that you happen, you'd better make sure that everybody gets it if anybody does.
- belval 5y ago
  Equality is great, but the situation would be no different than someone having access to healthcare/higher education/equal opportunities. After a few decades that technology would become commoditized just like everything else. It's not as if it was impossible to enforce regulations around that sort of thing.

Gatsky 5y ago

Impressive study, kudos to the bioinformaticians who did this! This could be an option for parents with a genetic condition who don’t want to pass it on. In terms of gattaca style super people (which I find quite repugnant) the recombination events are still random at the end of the day, so you’d have to screen quite a few embryos and there would be trade-offs. If you were really serious about it, the process would start with selecting partners based on their genetic fitness, and also using young fathers.

bradleyjg 5y ago
This could be an option for parents with a genetic condition who don’t want to pass it on. Most of the genetic disorders we know about can already be screened for (those that involve a single gene). This opens the door for polygenic screening but the underlying patterns to screen for are, in most cases, only weakly understood. We’d need to do a lot more research on adults with these diseases to get to the point where we can select against them in embryos. On top of that the amount of selection we can do is limited by the number of embryos to choose between. In many cases that’s a very small number.
- Gatsky 5y ago
  There are quite a lot of less severe conditions which aren’t easily testable on an embryo. That was the motivation for the research as I understand it. The whole polygenic thing isn’t very compelling, I agree.
  - bradleyjg 5y ago
    My understanding is monogenomic testing has gotten very extensive as well as less expensive and faster. It’s gotten to the point where if you can get genetic samples from the parents and all grandparents the only limitation is knowing what to look for.
- oneoff786 5y ago
  I’m starting to look into this. We have a single uncommon mutation to deal with, that’s just a fairly large cancer risk. Early advice has been that it’s still pretty hard to do single gene mutation screens. Needing samples from multiple relatives with the mutation to build a reliable screen.

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programmertote 5y ago

Coincidentally, I have a friend who is in the second cycle of this IVF procedure to select an embryo that does not carry the genes associated with polycystic kidney disease (PKD). When I heard it last week for the first time, I thought it is already an established procedure. Here, I'm learning that it is a relatively cutting-edge approach and I am now looking forward to asking my friend more about this next time we meet.

llebttam 5y ago
Commercial products in the space have been around for several years but can only screen for a small number of genetic diseases at a time. For example, Natera's Spectrum screens for chromosomal abnormalities (eg Down Syndrome) plus one custom genetic problem for a single condition of greatest concern. https://www.natera.com/womens-health/spectrum-preimplantation-genetics/ https://www.natera.com/womens-health/spectrum-preimplantatio... Some polygenic screening services that look at a much larger number of conditions are just reaching market now (eg Orchid Health), though our ability to map genes correlated with polygenic traits to phenotype results is still in its early stages. https://www.orchidhealth.com/ https://www.orchidhealth.com/

WheelsAtLarge 5y ago

Anyone know of any unexpected consequences of using this for IVF? It seems to me that we are falling into brave-new-world territory without really trying. I'm sure parents will do this to help their kids but I wonder what the negative issues will be? Gender selection is one but that's already being done by other means. What will this particular technology bring?

musicale 5y ago
The Gattaca premise sounds pretty logical but not unexpected. Presumably they will optimize for what they might view to be "favorable" genes associated with preferred traits (skin/hair/eye color, beauty/symmetry, strength, height, intelligence, disease resistance, aggression, etc.) while attempting to eliminate the others. This will (possibly) convey an increased "genetic" advantage upon the wealthy and privileged, while reinforcing societal structures that punish and exploit those who haven't been engineered the same way.
- WheelsAtLarge 5y ago
  Good point, people don't realize it or admit it but being born with what society defines as beautiful features gives a person big advantages in life. It's like hitting the lottery as far as advantages vs someone that's not. If you're already wealthy you'll be able to buy those advantages for your kids. It will be one of the greatest inheritance parents can give them.
- 0ldskool 5y ago
  Well the governments job is to create laws to make it easier for humans to live together. Even if Gattaca style gene selection is available, laws can be put into place to prevent discrimination. I.e. it is 100% illegal to do genetic testing for anyone other then yourself or your under-aged children. Those tests can only be done by a doctor and cannot be transferred or shared with anyone other than another doctor. Any employer or person that attempts to do a genetic test on someone can face jail-time.
ravi-delia 5y ago
Check out Gwern's analysis(https://www.gwern.net/Embryo-selection https://www.gwern.net/Embryo-selection) of this kind of technology. It suggests a somewhat noticeable effect, but not a particularly large or worthwhile one. That doesn't factor in new technology, but the methodology is all there so it shouldn't be too hard to plug in the new values. I haven't done that yet, but I'd be surprised if there was a big shift.

flobosg 5y ago

The actual paper: https://www.nature.com/articles/s41591-022-01735-0 https://www.nature.com/articles/s41591-022-01735-0