[HN Gopher] Scientists say they can read nearly the whole genome...
___________________________________________________________________
Scientists say they can read nearly the whole genome of an IVF-
created embryo
Author : Metacelsus
Score : 61 points
Date : 2022-03-21 16:40 UTC (6 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| throw0101a wrote:
| _Gattaca_ here we come! \o /
|
| * https://en.wikipedia.org/wiki/Gattaca
|
| :)
| monkeybutton wrote:
| Onwards to the Eugenics Wars and then the post scarcity
| Startrek future!
| [deleted]
| whatshisface wrote:
| 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
| legalcorrection wrote:
| 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.
| unsupp0rted wrote:
| 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 wrote:
| 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 wrote:
| 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.
| jacquesm wrote:
| A 120 average IQ population would be normalized to a 100
| average IQ population.
| legalcorrection wrote:
| Is this a joke? Yes, by definition an IQ test is
| normalized to 100 for the population it's targeted for.
| But that doesn't mean that you can't compare intelligence
| across different populations, by not doing that
| normalization.
| jacquesm wrote:
| Average IQ will always be 100, but 100 today is not the
| same as 100 50 years ago. Renormalization is about 3
| points per decade, so you have to take that into account
| when you compare IQ results across longer time spans.
|
| So a person that would have scored '100' on an IQ test 50
| years ago would be expected to score about 85 on a test
| administered today. Note that I'm not a fan of collapsing
| everything about human intelligence to a single number,
| but if you are going to use that number then you at least
| should be aware of how it is defined and how it develops
| over time.
| bpodgursky wrote:
| Redefining what 100 IQ means is a distraction (which
| feels like a malicious distraction) from the actual topic
| here.
| unsupp0rted wrote:
| The average IQ in Singapore is 105 and next door in
| Malaysia is 88.
|
| Singapore does run circles around Malaysia on most
| measures.
|
| The hard part is attributing any of this to average IQ, or
| determining if average IQ has been measured accurately
| enough.
| ch4s3 wrote:
| We don't have a very good understanding of the genetics of many
| of these traits. Intelligence is especially thorny, involves
| numerous genes, and is probably only about half hereditable
| which is actually reasonably high.
|
| We're likely to get a bunch of tall people, until everyone
| remembers they die younger due to cardiovascular strain. We'll
| probably wipe out most single gene hereditable diseases, which
| will be great. We're also somewhat likely to see fads around
| eye color in "designer" babies. We may also get people
| selecting for a single gene that make for great endurance
| athletes.
|
| Anything much beyond that is science fiction in the near
| future. The knock on effects of tinkering with more than a
| handful of well understood genes is going to be really
| dangerous.
|
| Quick Edit* There are around 1000 genes that have some bearing
| on intelligence. The 22 most impactful together account for 5%
| of variation.
| dekhn wrote:
| This is sort of naive. Even the chinese have backed off from
| their plans on doing this, both before and after the Jiankyu
| debacle. https://singularityhub.com/2013/03/19/chinas-bgi-to-
| sequence...
| https://www.technologyreview.com/2015/08/20/166465/is-it-pos...
|
| By the way, I spent about 20 years of my life pursuing this
| goal, and I've concluded that most cultures aren't that keen on
| superintelligent babies right now.
| evan_ wrote:
| > 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.
| 015UUZn8aEvW wrote:
| Embryo selection based on genome sequencing is already being
| done:
|
| https://astralcodexten.substack.com/p/welcome-polygenically-...
| dekhn wrote:
| Your example is "genetic" testing- it only samples a limited
| number of locations in the genome. This method is more like
| whole genome sequencing.
| belval wrote:
| 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.
| vsef wrote:
| Some people do choose to have deaf children:
| https://jme.bmj.com/content/28/5/283
|
| There was quite a bit of outrage around that case from hearing
| people, but it seems no different than two parents with genetic
| deafness choosing each other and then not trying to use genetic
| testing/embryo selection to have a hearing baby.
|
| I do think when this type of genetic manipulation becomes
| possible/mainstream there will be many traits chosen by parents
| that aren't considered universally desirable.
| Scarblac wrote:
| Blind or deaf people would probably feel pretty bad hearing
| "you don't want a blind or deaf kid".
| whatshisface wrote:
| That's a phrasing-based argument, it disappears if you
| replace it with "you don't want your kid to be deaf or
| blind."
| belval wrote:
| I don't think there's anything wrong with having a blind or
| deaf kid. I take issue with the idea that given the
| technology we would refuse to fix their disability before
| they are born.
|
| Try explaining to your son or daughter that they could've
| been able to see and hear, but you refused to avoid hurting
| the feelings of existing blind and deaf people...
| bobthechef wrote:
| whatshisface wrote:
| > _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.
| belval wrote:
| 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.
| mywittyname wrote:
| Those kids would still potentially breed the normal way. If a
| rich kid knocks up a bunch of poor ones, those children will
| have similar genetic advantages.
|
| And rich people fall from grace all the time. It's difficult
| for families to hold onto their wealth over successive
| generations. One of the keys to maintaining wealth is to keep
| it from being diluted, which means that some kids are going
| to get cut off.
| thegrimmest wrote:
| Doesn't that just mean that the bar for "greatness" will have
| risen? Isn't that a net gain?
| whatshisface wrote:
| 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.
| [deleted]
| [deleted]
| workaccount21 wrote:
| Because we have no idea how any of this works, selecting
| against one gene may have negative externalities that we don't
| even know how to measure. For example: a genetic cure for
| schizophrenia also dulling the creative traits it's correlated
| with. We cant even really understand how an emergent property
| like language works (see: every conlang), and you think we can
| engineer a civilization to be better by radically altering the
| balance of potential equality that we have been genetically
| optimized for?
|
| A society of 120 IQ adults would probably be an insufferable
| hell beyond comprehension, considering the track record of
| intellectual movements and the proclivity of smart individuals,
| probably like yourself, to vastly overestimate the merits of
| rationality and concepts that can be limited to the mind of one
| human.
| ALittleLight wrote:
| That's a good argument for not engineering all children all
| at once - we don't understand the consequences. It seems like
| a good argument for starting to engineer a few children so we
| can start to learn what the consequences are. As engineering
| becomes more palatable to the general population we will
| better able to deliver good results.
| whatshisface wrote:
| _Engineering_ children would likely introduce horrible
| diseases because as you say, nobody understands the
| consequences. What 's being proposed is selection, the
| selection of embryos which have already proven themselves
| to be viable and passed several steps of Nature's disease
| filtration.
| ALittleLight wrote:
| I'm using "engineering" in a sense that encompasses
| informed embryo selection. I don't think it's "likely" to
| have horrible results.
| belval wrote:
| > A society of 120 IQ adults would probably be an
| insufferable hell beyond comprehension, considering the track
| record of intellectual movements and the proclivity of smart
| individuals, probably like yourself, to vastly overestimate
| the merits of rationality and concepts that can be limited to
| the mind of one human.
|
| Disregarding the personal attack (I am well aware of
| downsides, but it's called having a discussion), higher
| median IQ is not really the point, it's about giving the same
| chances to everyone.
|
| We could use this to eradicate a wealth of issues that we do
| understand, there's no good reason to have babies born with
| Cystic Fibrosis, we know what genes are causing it.
| riskQtempAcc wrote:
| (Use of the pronoun "you" as the impersonal)
|
| You're not curing cystic fibrosis, or any other genetic
| disease, are you? You're just stopping disabled people from
| being born because you've decided their lives have no
| intrinsic value.
|
| This can be said to a wide swath of people. Down syndrome
| people, bipolar people, blue people, people with physical
| deformities.
|
| Why do you get to choose? Have you ever asked one of these
| people if they find their lives to be meaningless? How
| about their parents?
|
| I can think of few hells more dull than a world of smart
| ass public radio listeners providing unrequested comments
| lathered in snark and cynicism.
| whatshisface wrote:
| > _there 's no good reason to have babies born with Cystic
| Fibrosis, we know what genes are causing it._
|
| IVF is expensive and difficult and all easily identified
| genetic diseases are rare, so until one of those conditions
| changes (cost reduction and better techniques, or so many
| diseases being discovered that the odds that you will be
| saving your kid from one become significant), it will not
| be used for this purpose but rather as something extra to
| do when IVF is required for other reasons.
| belval wrote:
| We agree on that part, I am not advocating for editing
| every foetus' genome in the next 10 years. I just think
| it's short-sighted to put a ban on that kind of research
| based on fear of inequalities.
| whatshisface wrote:
| > _A society of 120 IQ adults would probably be an
| insufferable hell beyond comprehension, considering the track
| record of intellectual movements and the proclivity of smart
| individuals, probably like yourself, to vastly overestimate
| the merits of rationality and concepts that can be limited to
| the mind of one human._
|
| The world is full of societies of 120 IQ individuals. That
| would be, like... a typical office full of programmers.
| That's 1 in 10 people. Even 145 is 1 in 1,000. This gene
| stuff could only begin to surpass what you'd be able to do by
| holding a conference in an academic field at... 170? 180? For
| the foreseeable future the kinds of selection that operate on
| full-grown adults will greatly surpass this other kind which
| is limited to four or five embryos.
|
| In so many words, more than four or five former embryos are
| selected between in a typical round of SWE interviews.
| mywittyname wrote:
| >A society of 120 IQ adults would probably be an
| insufferable hell beyond comprehension
|
| > That would be, like... a typical office full of
| programmers.
|
| Is this an argument in support of the OP?
|
| Anyway, much like with global warming, the issue isn't so
| much the averages, but the impact on the extremes. Now the
| world suddenly has 10x as many 140 people or 100x as many
| 160s, etc.
|
| This cuts both ways too. A smart person isn't necessarily a
| nice person. A 20 point IQ increase could make the
| difference between someone who is a successful telephone
| scammer, and someone who brings down entire economies.
| taylorius wrote:
| >>an insufferable hell beyond comprehension
|
| >That would be, like... a typical office full of
| programmers
|
| Well, quite... ;-)
| bpodgursky wrote:
| Spend a week in a workplace with an average IQ of 80 and
| get back to me about which feels worse.
| Gatsky wrote:
| 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 wrote:
| _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.
| programmertote wrote:
| 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 wrote:
| 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-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/
| [deleted]
| Flatcircle wrote:
| 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 wrote:
| It only has to be better than random, right?
| jacquesm wrote:
| Indeed. And it could be worse.
| TOMDM wrote:
| 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 wrote:
| 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
| topynate wrote:
| 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 wrote:
| I think what people are worried about is that parents may
| neglect to take measures they otherwise would based on
| overconfidence in genetic screening.
| [deleted]
| exdsq wrote:
| What's the choke point of scanning an entire genome? Is it purely
| computational? Imaging? Biological unknowns?
| jkingsman wrote:
| 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-
| sequencin.... [2]: https://en.wikipedia.org/wiki/Single-
| nucleotide_polymorphism
| exdsq wrote:
| Thanks for your response! So is it true to say every genome
| could be sequenced, assuming time and money isn't an issue?
| dekhn wrote:
| 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.
| timy2shoes wrote:
| 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/bioinforma
| tics/article/30/22/3159/2...
| tux1968 wrote:
| 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.
| inciampati wrote:
| Different grades of sequencing are basically down to the
| technology and depth.
|
| The short read sequencing you're describing makes reads that
| are like motes of dust in comparison to the genome.
|
| More modern long read methods can read off sequences with
| high accuracy and/or length. These tend to be much higher in
| cost and substantially higher in the completeness and quality
| of the resulting bioinformatically inferred genome.
| jfengel wrote:
| _Average WGS times for something a person can buy for a
| couple hundred dollars take a few weeks,_
|
| I hadn't realize that we'd actually gotten the $1,000 genome.
| It was a big point of discussion 20 years ago, but seems to
| have arrived without the fanfare I would have expected.
| According to Wikipedia, it's been around for a few years, and
| claims the X-prize for it was canceled before that since it
| no longer looked like much of a challenge.
|
| So we sailed right through it and are now pushing an order of
| magnitude below that. Thanks; I had missed it.
| gwern wrote:
| As someone who was interested in projecting that back in
| like 2013 and watched the $1k arrive, I got the impression
| that it never became headlines in part because there was
| never a crystal-clear moment for the "$1k genome".
|
| Someone spends $1k and gets back a DVD of data ~2017. Well,
| is that $1k just the cost of the reagents? What about
| storage/assembly/analysis? How many samples did you run in
| that batch? Are you including the amortized cost of the
| sequencer (what utilization, discount rate, and upfront
| cost)? Are these long reads or short reads? To what depth?
| (There being energetic advocates for low depth / few passes
| + imputation.) Is this list price or institutional bulk
| price? Did Illumina give you a special deal (everyone knows
| they have hefty margins)? Are you even allowed to talk
| about the cost by Illumina? And so on. If the genome were
| $100k, or $10k, these could be rounded off, but as the cost
| drops, these nuisance factors become ever more of the
| price.
|
| There just was never a specific moment where you could
| write a headline "$1k Genome Arrives At Long Last!", and by
| the time you get Dante Labs doing consumer sales for $500
| or whatever (as long as you don't mind waiting half a year
| for the results), it's a bit late to write any articles as
| it is no longer 'news', now is it? So, people just stopped
| talking about the $1k genome because it had arrived quietly
| in the night, and switched to the $0.1k genome. And then
| you get similar issues, like that '$100 genome' BGI
| announced the other year - yes, there's a '$100' number
| there, kinda sorta, but there are so many caveats and
| questions that it discourages anyone from saying 'the $100
| whole genome is here at long last!'
| [deleted]
___________________________________________________________________
(page generated 2022-03-21 23:01 UTC)