Chinese scientist who edited twin babies' genes jailed for 3 years
lite.cnn.io
lite.cnn.io
Quick reply with a false equivalency!!
Statistically cas9 is barely worse than just be born to a late parent.
Depends on what's being mutated. It seems likely that 1. random mutations with catastrophic outcome would be negatively selected for evolutionary, 2. Humans try to meddle with genes that may be disproportionately important.
So I'd put the risk of gene editing quite a bit higher.
Given China’s almost unique state capacity to think long term, history of eugenic policies in sport, an ironically less Lysenkoist population than America, and a cultural focus on educational achievement and competition, this seems overdetermined.
In fact, animal breeders are getting very keen on iterated embryo selection. So the technology will get investment even in environments where it is illegal for humans.
We live in interesting times. Even a 2 standard deviation increase would allow a small population to produce the vast majority of genius-level intellects. 2 standard deviations is on the way low end of what iterated embryo selection offers. Should we find the causal variants, direct editing offers vastly more.
A world-wide ban on this technology is not on the table. Plan accordingly.
Obviously, this is not an issue if there is state involvement.
Example:
>A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes.
There's also been large studies that have used years of educational attainment as a moderately-correlated proxy for IQ.
The abstract does not mention that; they claim:
"This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population."
I don't think anyone would seriously claim that high IQ is mostly not caused by genetic variants, given the prior knowledge of the heritability of IQ.
In the conclusions section they state:
>Focusing on the core 4-test g measure, we think that accounting for 1.6% of the variance of intelligence is exciting for several reasons. First, this effect size is greater than the effect sizes from previous GWA studies of the normal range of intelligence.45 The effect size of 1.6% represents >2.5% of the heritable variance of intelligence, which is comparable to the most robust effect sizes in behavioural research.46
That they are "excited" to account for at best 2.5% of high IQ through genetics suggests that genetics is not a large contributor to high intelligence.
Previous studies demonstrating high heritability of IQ did not discriminate between genetic inheritance and social/cultural/environmental inheritance. Clearly, the latter are more significant contributors than is genetics.
Bit of a stretch there mate; that doesn't follow at all.
Accounting for 2.5% of the intelligence variation through genetics does lead to the conclusion that 97.5% of high IQ is not accounted for by (known) genetic variation.
What the important factors are is obviously an interesting question.
This simply isn't true. Studies of twins not raised together provide evidence that IQ is more than 50% heritable. https://onlinelibrary.wiley.com/doi/epdf/10.1002/neu.10160
Strict genetic heritability studies do not support a stong association of genetics with intelligence.
So your your citation does not support a strong link between genetics and intelligence?
No. It does not mean that. As I literally just explained to you: a specific PGS variance != SNP heritability != heritability. (How could you possibly think that when I also just explained to you in my other comment that the current IQ SOTA is 11% and you replied acknowledging as much?) The best estimate of intelligence heritability in adulthood at the peak, using measurement-error-corrected estimates, is 70-80%. Very far from 3.5%. Or 11%, or 30%, or 50% for that matter.
For genetic factors alone, the consensus so far is that there is very weak correlation of genetic variation with intelligence, unless a not quite-yet-established polygenic score is constructed. To wit:
>From the 1990s until 2017 no replicable associations were found. GPS from these early GWAS, which we refer to as ‘IQ1’, predicted only 1% of the variance of intelligence in independent samples. It became clear that the problem was power: the largest effect sizes of associations between individual single nucleotide polymorphisms (SNPs) and intelligence were extremely small, accounting for less than 0.05% of the variance of intelligence.
However, things got "better":
>in 2016, a second meta-analytic GWAS analysis with a sample size of 294,000 identified 74 significant loci30. This analysis produced a GPS, EA2, that predicted 3% of the variance in years of education on average in independent samples30.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985927/
It stretches the imagination how one would go from these numbers to claiming that "The best estimate of intelligence heritability in adulthood at the peak, using measurement-error-corrected estimates, is 70-80%.
No, it doesn't. Heritability is intended and defined to include genetic factors only, unless you are referring to indirect genetic effects which are mediated through the environment but are still genetic in origin.
> For genetic factors alone, the consensus so far is that there is very weak correlation of genetic variation with intelligence, unless a not quite-yet-established polygenic score is constructed. To wit:
You are again being extremely misleading and selective in your quote-mining, and you omit all of the qualifiers that Plomin & Stumm include, eg "Recent genome-wide association studies have successfully identified inherited genome sequence differences" - 'identified genome sequence differences' does not imply that they are the only genes involved. Merely that some have been identified, and more will be. As they then go on to point out in the parts of the review you ignore, future GWASes will surely make much more progress in identifying SNPs, and approach the SNP heritability ceiling of ~30% given enough data.
> It stretches the imagination how one would go from these numbers to claiming that "The best estimate of intelligence heritability in adulthood at the peak, using measurement-error-corrected estimates, is 70-80%.
Er, because I'm not talking about SNP heritability estimates. I am talking about estimates from twin studies, adoption studies, and MZA studies, which estimate total genetic contributions. The lower-bound is 50%, you don't get anything lower from any twin studies, and this is deflated by the fact that many twin studies are looking at young kids and the Wilson Effect has not yet kicked in; this is then further deflated by the fact that they use noisy IQ measurements, which inflate the error variance component and hide the shared-environment/heritability components. Correct for those, and you get up to 70-80%. All of this is covered in the Plomin textbook cited there, starting pg171, where they cover things like how MZA designs deliver 72% heritability estimates and they explicitly mention that measurement error biases downwards ('Corrected for unreliability of measurement, heritability estimates would be higher...'). They are being highly conservative by using a lower bound of 50%, and they are wrong to, because as I already mentioned family-GCTA/GREML-KIN indicates that semi-rare variants alone get you up to 50% heritability, so we can be sure that 50% is a considerable underestimate (which is consistent with their expanded textbook discussion noting that the real heritability is much higher).
-Other models of intelligence as wrong and g is real because tests results correlate with each other, which is completely orthogonal to Shalizi's point. Because of the very nature of testing the results are going to correlate with each other; the most trivial example is, using Taleb's example, if dead people take the test. Dead people are dead and have an IQ of zero, and this is enough to increase the correlation (https://twitter.com/nntaleb/status/1114977580053147648).
-Apparently confirmatory factor analysis means g is relevant because...confirmatory factor analysis means g is relevant? Nothing addresses the fact that g could be an artifact that arises in any set of measures that correlate with each other regardless of the origin. Adding to that, there is scant evidence of any link between g and the underlying neurobiology and/or actual causal genetic mechanisms, beyond very trivial cases such as obvious malformations etc. On the contrary, neurological findings are pointing to the opposite direction (https://www.ncbi.nlm.nih.gov/pubmed/23259956).
-Even if we have no idea how g works it's still useful for predictions for stuff like educational attainment so it's relevant. Well duh, if you're good at taking tests you're going to do well in an environment where your attainment depends on your doing well in tests. Again, there is enormous circularity in reasoning. And as for the other outcomes, look at it this way: you could combine many measurements from your body (say, various analyzes from blood samples, but even trivial things like number of legs or amount of blood in your body could do), find they all correlate with each other (because when your body is breaking down it is likely damage to one organ that's spreading damage to other organs etc.), and from all that stuff you could draw a general "health quotient", or HQ. It would be highly heritable, there would be literal millions of SNPs that are associated with it. It would have immense predictive value for a variety of social outcomes. Does this mean that HQ reflects a unidimensional, physical reality in your body? Does this mean medical practitioners would have any use of it? And more crucially, does this mean that attempting to optimize for it (as opposed to, you know, optimize for actual real things that we can readily see) wouldn't be an utterly fruitless endeavor?
One last thing, since people seem to love brandishing GWASes around like a magic wand: people in the community are becoming increasingly disillusioned with them these days. (The head of EMBO, Ewan Birney, recently spoke about this. Note that I'm talking about academic geneticists, not the small clique of psychologists/"independents" from institutes with shady funding whose names invariably pop up when dealing with the less savory elements of the debate.) Again, for a geneticist, you need to find an actual genetic mechanism to prove something is "genetic", otherwise you end up with ludicrous associations (https://twitter.com/SbotGwa/status/1151964472921219073, or a GWAS for type of fat used in cooking). This has not deterred people from less rigorous fields such as psychology to attempt to GWAS for literally anything. A charitable interpretation is that people conducting such studies are unusually naive, a less charitable one would be to draw connections among the aforementioned small clique and correlate them with the views people in said clique have expressed, and reasonably infer that a motivated agenda might be at play here.
Of course I'm not looking to convince you since you appear to have read a truly gigantic amount on the subject and probably have a list of well-prepared rebuttals for literally any argument so that anyone with less time for online posting would never have the last word, so this is more of a post for any passer-by who'd think that IQ has any relevance beyond some niches of psychology. It's certainly not a thing in mainstream popgen or any field of genomics and if someone presented an abstract at any conference dealing with the kind of stuff posted on humanvarieties they'd be laughed out of the room.
No, it's not. There is no reason whatsoever that there has to be a positive manifold, attempts to construct batteries without it have failed, this is one of the most important empirical reasons for g, and you leading with this point demonstrates you didn't even bother to read the rebuttals to Shalizi.
> -Even if we have no idea how g works it's still useful for predictions for stuff like educational attainment so it's relevant. Well duh, if you're good at taking tests you're going to do well in an environment where your attainment depends on your doing well in tests. Again, there is enormous circularity in reasoning
This ignores the enormous number of correlations (and causality, via PGSes in within-family settings) with everything from brain volume to longevity, and also the fact that adding education as a mediation does not eliminate those correlations. The only circularity here are the strawmans you are erecting.
> It would be highly heritable, there would be literal millions of SNPs that are associated with it. It would have immense predictive value for a variety of social outcomes.
The heritability of longevity is actually quite low. You should think about why your thought experiment didn't work.
> The head of EMBO, Ewan Birney, recently spoke about this.
Birney is deeply ignorant. He makes mistakes all the time. For example, he claimed recently that embryo selection had never been done, not even in animals; actually, it's been done commercially for years. Or his most recent op-ed, where he confused SNP heritability with heritability and claimed that demonstrated that 90% of income is 'environmental' (a misunderstanding all too evident in this thread) - so embarrassingly obviously wrong even his geneticist friends had to correct him and he issued a mea culpa. You shouldn't take your beliefs about 'disillusionment' about GWASes from a guy who doesn't even understand the basics about them and spouts off claims that he didn't spend 30 seconds googling.
> Again, for a geneticist, you need to find an actual genetic mechanism to prove something is "genetic", otherwise you end up with ludicrous associations (https://twitter.com/SbotGwa/status/1151964472921219073, or a GWAS for type of fat used in cooking).
No, you don't. This is an extremely narrow conception of things. Preferring a specific type of fat in cooking is no more ludicrous than, say, preferring tea to coffee (which is heritable and the GWAS works fine for).
> Of course I'm not looking to convince you since you appear to have read a truly gigantic amount on the subject and probably have a list of well-prepared rebuttals for literally any argument so that anyone with less time for online posting would never have the last word, so this is more of a post for any passer-by who'd think that IQ has any relevance beyond some niches of psychology.
Passerbys should take into consideration the quality of evidence being cited by this throwaway account, and to what extent they appear to have not read a truly gigantic amount on the subject, when they read sweeping descriptions of what 'academic geneticists' think etc.
> It's certainly not a thing in mainstream popgen or any field of genomics and if someone presented an abstract at any conference dealing with the kind of stuff posted on humanvarieties they'd be laughed out of the room.
Results from SSGAC etc are extremely mainstream. They are published in Nature and similar outlets. Papers use IQ/EDU PGSes and the genetic correlations all the time for many purposes. Look at the reverse citations for papers like Okbay or Selzam. 'laughed out of the room' indeed!
Yes, there is. You didn't understand Taleb and Shalizi's point obviously. Look at the tweet.
>This ignores the enormous number of correlations (and causality, via PGSes in within-family settings) with everything from brain volume to longevity, and also the fact that adding education as a mediation does not eliminate those correlations. The only circularity here are the strawmans you are erecting.
"Adding education as a mediation" does a lot of work in this sentence here.
>The heritability of longevity is actually quite low. You should think about why your thought experiment didn't work.
Where in the world did I mention longevity?
>Birney is deeply ignorant.
Lol, so the head of the most prestigious center for genetics in the world is ignorant. Is Graham Coop ignorant as well? How many genomics professors are ignorant then? Also you didn't even bother to research what he actually said. He protested in response to the disillusion about GWASes from the community (again, we're talking about the community of academic geneticists with a PhD in biology, not social scientists or psychologists) and he was in favor of some of their predictive power.
>No, you don't. This is an extremely narrow conception of things.
Yes, you do. You have obviously never stepped in a single genetics lab or done any actual academic research if you think otherwise. That's how genetics works: you've got to show a genetic mechanism to show something is genetic. It's like the "all biologists are from Missouri" thing. GWASes suggest things, they may nudge in a direction, but they do not prove. This is like basic stuff.
>Preferring a specific type of fat in cooking is no more ludicrous than, say, preferring tea to coffee (which is heritable and the GWAS works fine for).
It's absolutely ridiculous and if you don't think otherwise I don't know what to tell you. The fact that you can GWAS for literally anything should be evidence against their predictive power, not for it.
>Passerbys should take into consideration the quality of evidence being cited by this throwaway account, and to what extent they appear to have not read a truly gigantic amount on the subject, when they read sweeping descriptions of what 'academic geneticists' think etc.
I use throwaway accounts because I can't be bothered to remember my password for this site. And, in case it wasn't obvious, and anyone may feel free to believe me or not: I happen to do genomics research for a living. It's literally my job, and I interact, for better or for worse, with hundreds of similarly minded people who do similar things. I didn't bother to read psych papers from 1983 but I do know the mainstream consensus, in 2019, in the genomics community (again, not in the social sciences).
>Results from SSGAC etc are extremely mainstream. They are published in Nature and similar outlets. Papers use IQ/EDU PGSes and the genetic correlations all the time for many purposes. Look at the reverse citations for papers like Okbay or Selzam. 'laughed out of the room' indeed!
Again, SSGAC is a social science institute. And again, doing a bunch of GWASes to "predict" (the word is used loosely) social outcomes is not how actual biology works. No, rallying behind the magic card "but I controlled for things!" does not work either. Biologists now how complicated things can be and are very hesitant to put forward causal mechanisms behind even minor, uncontroversial traits unless they're absolutely sure of what they're doing, and it usually involves tremendous amounts of money and often new technologies. That a bunch of social science guys put forward such very bold conclusions (involving, once again, a very distorted meaning of the word "predict") without batting an eye should tell you more about the researchers' bias than the "insight" they purported to discover.
Again, you just try to get a talk at the Biology of Genomes in CSHL or at the EMBL about the heritability of preference for cooking oil, see how that works.
It would be bad enough if you were linking to a rebuttal of the post on heritability linked to by the parent, but this is a blog post attacking a different post by Shalizi.
How is this in any way relevant? More importantly, why would this convince anyone that Shalizi gets heritability wrong?
The enriched population tends to have a higher population of these common variants. Saying it "does not help" is kinda silly-- the authors and reviewers behind this Nature MP pub disagree with you, as do I ;)
In the end, we have small randomized sample studies directly on IQ; enriched case-controlled studies like this one; and large studies looking at proxy variables (educational attainment). They have all come up with broadly similar estimates for the effects of polygenic variation on general intelligence. That is, we have enough information to be reasonably confident in an upper bound.
This is not a problem for embryo selection.
1. a polygenic score is not 'the impact of common variants'; that's the SNP heritability, such as the GCTA or LDSC. It's not 1.6%, it's closer to 30%. You edited out the part of the abstract which correctly specifies this: "the single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02)"
2. that is not the best predictor of intelligence; it is not now (that would be Allegrini et al 2018), and it was not then either - you have to go all the way back to like 2014 for 1.6% to be SOTA and I'm puzzled why you cite Zabaneh at all, which is one of the most obscure IQ GWASes... The actual SOTA is 11% or higher.
3. your claims about power are obviously wrong, as Allegrini et al 2018 uses far less than 'tens of millions' and still greatly outperforms it. (Which has something to do with those rare beneficial variants not existing which they were looking for...)
So, we can predict 11%, not 1.6%, and common variants have a large impact, 3x that, and rare variants account for even more, easily 50% including what you might call semi-rare variants (https://www.biorxiv.org/content/10.1101/106203v2).
I think the lift in IQ you get from embryo selection is counteracted by a lot of other (negative) factors.
It is also unclear to what degree epigenetic inheritance plays in IQ. My opinion is the 8-10 IQ point boost is less than variance from unknown factors relating to doing IVF versus natural birth. In other words I would still go with natural birth (which has been time tested by evolution)
Nope. IQ is negatively correlated with most mental illness. It is certainly not positively correlated with schizophrenia: https://www.gwern.net/iq
As it turns out, we have multiple contradictory findings about whether high IQ is positively or negatively correlated with mental illness.
But even if you believe there's a negative correlation, it doesn't mean that many predictive SNPs can't predict both.
E.g. cloud cover is predictive both for rainfall and heavy snow. However, heavy snow is negatively correlated with rainfall. The latter doesn't negate the former.
I am by no means saying that the underlying traits are casually related — only that metrics which predict one may also predict the other.
The human brain is a complex system and IQ itself is a very simplistic way to characterize it.
Think of it this way: imagine IQ is like electricity powering a city. Different city configurations have very different power and load requirements. You might find that, in general, cities with more power function better.
But perhaps the well functioning cities also had better transmission infrastructure. If you applied the rule of “more power is better” to a city without that infrastructure it would blow fuses everywhere and cause chaos.
With this example aside, In fact the science does say that there is a relationship: https://www.nature.com/articles/s41380-018-0332-x?WT.feed_na...
Given China's complete disregard for human life, I don't find it odd that they're the ones doing it, but we should not praise the effort.
Apart from that I do believe, that in the future human gene editing makes sense. Once it is actually understood. (until then volunteers are allright with me, but experimenting with babys ... is a bit off)
Because we are successfully eliminating natural selection in various ways. But evolving works naturally through selection. Degeneration would be the long term effect, unless we find other ways. And improving our genes as we see fit ... seems to be a solution.
In the short term though, it seems like a good idea. Regardless, in a multipolar world we don’t have much choice in the matter.
"My gift to industry is the genetically engineered worker, or Genejack. Specially designed for labor, the Genejack's muscles and nerves are ideal for his task, and the cerebral cortex has been atrophied so that he can desire nothing except to perform his duties. Tyranny, you say? How can you tyrannize someone who cannot feel pain?"
- Chairman Sheng-ji Yang, "Essays on Mind and Matter"
I have no idea how you'd manufacture both a loyal and genius breed - what/whom are they loyal to?
"Bokanovsky's Process"... x-ray, and alcohol to clones of the "worker class" to make them slow and stupid to do your bidding.
Generational planning...who will be at the helm 20+ years later? "The Party"? Maybe if it was a Medieval Kingdom, but even then you'd wonder how that would affect the fighting spirit of the people. Might commit national suicide
This will probably happen in the distant future. Most of the genetic research this decade will be driven by national competition. it's an arms race
To back this up, at least this paper claims that the idea that natural selection is being referred inoperative in modern human populations is widely rejected by evolutionary biologists.[1] Changes in human society have actually accelerated selection for certain types of traits that we know of. For example, genes that help people deal with our increasingly unhealthy diet may be strongly selected for.
Chinese technological dominance seems likely even ignoring embryo selection. This will likely be amplified by better agglomeration in cities.
Were western institutions capable of thinking long-term, this would add to their desire for human enhancement.
Western institutions biggest advantage is the ability to easily leverage worldwide talent, which is incidentally China’s biggest deficiency. A lot of China’s human capital, for example, has helped with the success of America’s tech industry.
Humans can be enhanced in other ways that don’t involve messing so finely with Mother Nature. We can simply develop and use better tools, for example.
Let a hundred flowers bloom, as they say.
Beijing is presently a dictatorship. It is making the classic short-term decisions associated with placing personal political survival over national imperatives. (It made terrific capital investments between Xiaoping and Jintao. But the incentives changed with Xi for life.)
What makes China uniquely positioned with respect to human genetic engineering is its willingness to treat its population as test subjects. That’s a huge advantage, albeit one with the predictable downsides.
It's either for show, or perhaps to punish/keep him for publicizing the national superhuman program
Not content with simple fraud charge, those guys always go for complete demonisation of the persona accused and self-denunciation.
Had he given more of those to the government officials and/or jurisdiction, he wouldn't even have to face the charges in the first place.
> Zhang was sentenced to two years in prison and fined 1 million yuan ($143,000), while Qin was given a suspended sentence of one year and six months in prison and fined 500,000 yuan ($71,600).
I find many comments on this thread pretty despicable.
So, I guess they’re already trying on my future children?
"Comments should get more thoughtful and substantive, not less, as a topic gets more divisive."
Don't get seduced by the dream he was selling. He was in fact a fraud, not a researcher.
Endangered the health of two people