Scientists say they can read nearly the whole genome of an IVF-created embryo
science.org
science.org
https://astralcodexten.substack.com/p/welcome-polygenically-...
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.
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.
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.
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.
The whole polygenic thing isn’t very compelling, I agree.
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.
> 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%.
True Positive: non-viable, next embryo/round of IVF
False Positive: non-viable, next embryo/round of IVF
True Negative: Cool, parents move ahead with a healthy (in this regard) child.
False Negative: Parents move ahead with a false confidence.
Going in blind for muscular dystrophy, parents may hedge their bets by ensuring they live close to a school that can deliver against their childs needs, housing that is accessable (no stairs, easily accessable etc.), setting aside money for healthcare.
Of course the testing is only worse off in the case of a False Negative. I have no idea what the odds on that are, but I can imagine it'd be quite the shock for some people. In all I'm very bullish on the good IVF testing has the potential to do.
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
Source: I worked on the computational modeling of this problem in grad school, https://academic.oup.com/bioinformatics/article/30/22/3159/2...
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.
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.
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!'
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.
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/
Where all the women are strong, all the men are good-looking, and all the children are above average.
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.
Who knows, maybe our IQ 120 overlords will be kind to make the tech available for everyone else.
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.
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.
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.
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.
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.
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.
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.
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.
This doesn't set off your dystopia alarm?
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.
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.
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.
> 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?
My hope with this technology is that we can give prospective parents the kind of tools that allow them to make reproductive choices that best reflect their desires and hopes and dreams for their children. The question of course is what are they going to do with these tools? Will they eagerly use them or throw them away in disgust?
And then what do we do as a society in response to that?
Is it legal to feed your new born child alcohol? Is it legal for pregnant women to drink alcohol? Is it legal for two cystic fibrosis gene carriers to knowingly produce a child who will suffer from cystic fibrosis? Is it legal for someone to modify their embryo so that it turn into a child that will be a cystic fibrosis carrier? Is it legal for someone to modify their embryo so that it turn into a child that will suffer from cystic fibrosis?
Which of these things should be legal and which shouldn't? How do we enforce them?
I have a couple of disabilities and genetic diseases. They utterly, inarguably, and completely suck.
Presumably this "you" is the parent. They get to decide when (or if) they have kids and they can now decide what kind of kids they have. Just like folks can (and should) already screen for certain heritable disabilities.
> Have you ever asked one of these people if they find their lives to be meaningless?
They'll either be depressed or they won't feel this way. By definition, the ones that are well-functioning parts of society won't feel this way. I don't see why it should matter.
> 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.
For someone who finds that dull, there is a lot of snark and cynicism in this comment. It's really not necessary, we're all here to engage with each others' view points.
No. I explicitly stated that I was using “you” as the impersonal pronoun, which English otherwise lacks (although “one” is often used instead)
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.
> 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.
>That would be, like... a typical office full of programmers
Well, quite... ;-)
Or jazz musicians.
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...
more like try explaining to your son or daughter that they wouldn't have been born at all
I am legally blind. I would not want my children to have any disability whatsoever because it's difficult and miserable.
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.
Fear of the unknown and distrust of everyone else. This might give someone an advantage, so it must be bad for me. I view it kind of like metaphorical crabs trying to climb out of a bucket.
* https://en.wikipedia.org/wiki/Gattaca
:)
[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