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As every conference attendee knows, a few minutes with a researcher is worth many hours of reading their work. What researchers say in person will be up to date, generally unvarnished and to the point. Compared to writing, conversation is speedy, interactive, and tends towards confession: the spoken word accompanied by the revealed emotion, a multi-level signal, rich in content. Ambiguities can be probed with short queries about meaning and anything contentious subjected to rapid forensic examination, in a two-way process which homes in on core issues. All this would take weeks by email, and in 5 exchanges would lead to boiling rage on Twitter.

Minneapolis is a fine city, with an excellent gallery. Cranach knew a thing or two about the human condition.

ISIR2019 was a conference at which one was spoilt for choice, since within speaking distance over coffee one could chat with Charles Murray, Steve Hsu, James Lee, Greg Cochran, Greg Clark, Razib Khan, Bruce Lahn and Neven Sesardic and many others. At breakfast with Tim Bates I met an amiable couple and, assuming they were wild-variant humans who happened to be staying at the hotel, launched immediately into a general enquiry about life in Minneapolis. They were a sparky and fun couple, and later in the day I realized I had been giving car buying advice to Prof Tom Bouchard, a legendary figure in twin research.

Even better, all of the prominent researchers were excited to see so many younger researchers, whom they quizzed enthusiastically. There is an excellent crop of young scientists already making their mark, and they were the de facto stars of the event, because established participants are all too aware that a decade ago such new talent was rare: it was a conference for older researchers. (ISIR offers special inducements for researchers at the start of their careers).

The first day of the conference had a Symposium on Science and Ethics of genetic engineering, with Greg Cochran, Steve Hsu, Razib Khan, Bruce Lahn and Neven Sesardic. Sesardic argued that John Rawls’s work was a far from perfect guide to ethics in this field. Impossible to cover each contribution, but a general theme was that “designer babies” were unlikely, mostly because of doubts about unintended consequences. Crispr techniques are accurate for point deletions and small sequence insertions, but not so accurate when dealing with longer stretches of DNA. The panel as a whole was cautious about any gene editing procedures at this stage, though Razib Khan said that some in the genetics world, while condemning He Jiankui for his work on twin babies susceptible to HIV, were also grudgingly impressed with what he had done.

In answer to a question, Bruce Lahn said that genetic engineering in mouse was accurate, and came up with very few unintended effects, of the order of 1%. There was a common agreement among the panel that the appropriate ethical standards would prevent such experimentation in the West, but uncertainty about whether this would be the case in China. This raised a possibility that whichever nation relaxed ethical standards to allow experimentation might gain a considerable advantage over other, merely by the deletion of intelligence-lowering mutations. The panel also noted that screening for Down’s syndrome was now routine. In-vitro fertizilation was now running at over a million births a year, and these children has been previously stigmatized as “test tube babies”. Attitudes change if people are give the ability to choose new techniques.

This is a very brief summary, but here is the sequence as I see it, from those likely to happen soon to those much further downstream and happening later, if at all:

1) In countries where pregnancies can be terminated, more pre-natal screening, not only for Down’s syndrome, but for other forms of severe mental handicap and, when possible, for some genetic disorders like cystic fibrosis and Huntington’s chorea.
2) In the case of in-vitro fertilization, far more screening based on polygenic risk scores for a wider variety of disorders, concentrating initially on those with the very highest scores which put embryos most at risk. This depends on having viable foetuses to select from. No changes are made to the foetus, but choice is guided by polygenic risk scores.
3) Limited use of Crispr on foetuses to remove mutations directly linked to serious genetic disorders.
4) Crispr being used more generally to remove SNPs which increase vulnerability to a broader range of genetic disorders.
5) Crispr being used even more generally to remove SNPs which increase vulnerability to psychiatric disorders and low intelligence.
6) Crispr or other techniques being used to create “disease resistant” embryos.

Incidentally, one prominent researcher said that he and his colleagues were perplexed as to exactly what had been said at the London Conference which had caused so much trouble. I replied that I too was perplexed, but thought that it was because one of the 59 papers given at UCL was about eugenics, arguing it would only be contemplated in the setting of Malthusian over-population, and that it would not select for intelligence, but for a propensity to be happy. “Really” he replied “but that is far, far less than we have discussed here today”.

Strange are the ways of humankind.

• Category: Science • Tags: Genetic Engineering 
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  1. dearieme says:

    Down’s syndrome and selective abortion: it seems to me a wise thing to do if that’s what the parents want. That’s the whole purpose of the amnio, isn’t it?

    I don’t understand the American abortion wars. In particular, I don’t understand the people who are enthusiasts for abortion. Abortion reluctantly accepted as the lesser evil, fair enough. But abortion as a subject for enthusiasm: “weird”, as we youngsters say.

    I sympathise with the anti-abortionists on one point: Wade-Roe was a scandalously unconstitutional decision by SCOTUS. But that doesn’t seem to me to have any scientific import. It’s hardly news that the US Constitution doesn’t work properly.

    Anyway, at last, to the point: if aborting a Down’s baby is widely judged to be OK what other conditions are likely also to be judged OK as a reason for choosing to abort?

    • Replies: @davidgmillsatty
  2. Realist says:

    Strange are the ways of humankind.

    Genetic engineering can change that.

    • Replies: @Anonymous
  3. der einzige says: • Website

    such blah blah blah but it’s really all about
    step by step
    supposedly in the name of progress and crap like that
    to introduce human farming
    men will be custom-made
    bought as products
    the new brave world begins
    kind of human GMO
    soldier, athlete, worker, slave
    mascot for fun
    the new brave world begins
    kind of human GMO

    • Troll: Realist
    • Replies: @YetAnotherAnon
  4. After reading Jennifer Doudna’s book, Crack in Creation, I don’t agree with all the hand wringing about the rich people getting first access to germ-line editing. I say, let the wealthy have a couple of decades to experiment on themselves before requiring taxpayers to offer it to all.

  5. Lauro says:

    Thanks a lot. That was really informative.

  6. “Crispr or other techniques being used to create “disease resistant” embryos.”

    If it works as well as GMO seeds have…

    Will these embryos require companion “Roundup” infant formula?

    • Replies: @Anonymous
    , @J
  7. Anonymous[254] • Disclaimer says:

    Oh yes, certainly.
    Future humans are going to be engineered toward pristine integrity, fairness, tolerance and open-mindedness, among others.

    • Replies: @Realist
    , @Colin Wright
  8. Anonymous[254] • Disclaimer says:

    It’s already been, and it’s still going to be, unbelievably less easy than the more forward geneticists would have it.
    However, it may one day come true.

  9. Factorize says:

    Any word on an upcoming IQ/EA mega-GWAS? The EA GWAS from last July gave us 17 SD (250 points) of enrichment potential. There are now now tens of millions of genotype files that could be used to push us over the line. Might 400 or 500 additional points start people contemplating our future? One certainly could also wonder what cognitive potential humans now being genetically engineered in labs might have.

    • Replies: @James Thompson
  10. Realist says:

    Oh yes, certainly.
    Future humans are going to be engineered toward pristine integrity, fairness, tolerance and open-mindedness, among others.

    That is correct. Two of the most important human traits, integrity and intelligence can be vastly improved through genetic engineering, among others. Human traits are strongly controlled by DNA.
    Perhaps you should get educated on genetic science.

  11. J says: • Website

    GMO + Roundup is a successful combination and has changed food production -for good -in the last thirty years. That model is the way to go. In fact, already we have Celiac disease + gluten free food, and lactose intolerance + soy milk, and so. The “wild” phase of humanity is over, future generations will be so genetically modified that everybody will need some critical complement such as special food, drugs, surgical intervention or auxiliary machinery. CRYSPR or no CRYSPR, in a few generations they will be no more babies able to survive “naturally”. I am investing in gluten-free bakeries and searching for other conditions that necessitate their “Roundup” complement.

    Regarding the marshmallow test, no one has considered that maybe Africans like its taste more than others? Some people prefer sauerkraut over marshmallow. I do.

  12. @Anonymous

    ‘Future humans are going to be engineered toward pristine integrity, fairness, tolerance and open-mindedness, among others.’

    Redundant. Labrador Retrievers already exist.

  13. Encouraging news here, James, and reason for optimism – even as the theory of Idiocracy comes despairingly into view in lived time – that with the wide availability of low cost, government supported gene editing humanity may yet be up to adding some good measure to its achievements in science, art and engineering.

  14. Maciano says:


    Is it possible to visit such a conference as a non-academic? I would love to attend one of these some day. It’d be extremely interesting.

    • Replies: @James Thompson
  15. M Krauthammar [AKA "Laura McGrath"] says:

    Your grandchildren will be brown. Shut up, Bigots.

    • Troll: YetAnotherAnon
    • Replies: @silviosilver
    , @Loren
  16. pyrrhus says:

    Thanks for an incredibly informative summary, Dr. Thompson….One question…does anyone have an estimate for the likely costs/ per child? Governments are pretty much broke worldwide…

    • Replies: @James Thompson
  17. Laura McGrath: “Your grandchildren will be brown. Shut up, Bigots.”

    Since race differences cause strife, governments want to eliminate them. Genetic engineering will provide much more effective tools for doing this than leaving it to the chance results of long term race mixing. One way to do it would be to make everyone look the same. Whether that will be a stereotypically black or white appearance is for future generations to decide. As for today, can anyone doubt that if Current Year governments could eliminate race, they would? If you eliminate race, then you also eliminate that greatest of evils that plague the modern world, racism. Utopia, here we come!

    • Replies: @foolisholdman
  18. Factorize says:

    This is an absolutely terrifying idea! The technology that would allow for CRISPRing a desired skin color for one’s offspring is likely a near term possibility. There are only roughly 20 genes involved. Yet the psychometric view is that this should make little to no difference in IQ. Large differences in cognitive ability would still exist between ancestral groups, though one would then need a DNA test to identify group membership.

  19. @M Krauthammar

    Your grandchildren will be brown. Shut up, Bigots.

    Maybe. But blacks will still remain low IQ and impulsive, and burdens to any non-black population unlucky enough to be saddled with them.

    • Replies: @Mr. XYZ
  20. @Factorize

    I discussed this with researchers at the conference. Getting the number up to 1.7 million would be very time consuming, though the benefit is that it would cast more light on the evolution of intelligence. Personally, I think it would be a very worthwhile effort, but the researchers have to make their decision.

  21. @pyrrhus

    Well, no one is going to do any alterations at the moment, but just having a look at the relevant genome might be $2000. Then, once it is legal, and feasible, and wise, someone will offer the service, probably at a very high cost, simply because the implications and the insurance costs will be daunting.

  22. Loren says:
    @M Krauthammar

    typical lib. tell people to not vox their opinions.

    brown — read ‘negroes in negroland’

  23. Mr. XYZ says:

    If black dysgenic fertility trends will continue, then Yes, certainly.

  24. @der einzige

    “kind of human GMO”

    Maybe, but it’s swimming against a dysgenic tide in Western societies, who are both paying low-IQ people to have babies AND importing low-IQ people to have more babies. These things are in the control of governments.

    As for Dr Morgan’s “since race differences cause strife, governments want to eliminate them”, why then are Western governments (and only Western governments) importing different races if that’s true?

    The UK was pretty monocultural in 1950 (and even then there was strife with Irish/Welsh/Scots).

    I don’t see China or Israel doing it. They prefer to ‘eliminate race differences’ by having one dominant group in charge, and discouraging “problem” groups from having many children.

  25. YetAnotherAnon: “As for Dr Morgan’s “since race differences cause strife, governments want to eliminate them”, why then are Western governments (and only Western governments) importing different races if that’s true? ”

    Various theories have been proposed. Among them:

    1. “Hostile elites” want to breed out the white race by mixing it with non-white races. Under this theory, short term strife will nevertheless lead to a more docile, easily led populace in the future as whites are mixed out. This view sees whites as innately troublesome for the “hostile elites”, so they put high priority on trying to eliminate them. It’s essentially a conspiracy theory, premised on the idea that the importation of non-whites is being imposed on whites against their will.

    2. Elites, along with many or even most ordinary whites, sincerely believe that race differences are only superficial, and that once imported, non-whites will eventually adapt to white culture. This theory also relies on time to smooth over all differences, but envisions this happening mainly at the cultural level. Humanitarian motives are often cited as a reason for the importation; also economic reasons. This view sees whites as complicit in their own dispossession, either through greed (the economic reason) or “pathological altruism” (the humanitarian reason), or a combination of the two. This can be explained in several ways, some conspiratorial, and others not. It’s certainly consistent with the “brotherhood of man” nonsense that Christianity has taught the white man for two thousand years.

    Neither of these cases conflict with government-sponsored genetic manipulation in an attempt to eliminate racism.

  26. @dearieme

    Baloney about the case being scandalously unconstitutional. If the argument is that there was no right to privacy in the bill of rights, how about the third amendment which prevents the government from quartering soldiers in your house. If that is not a right o privacy I don’t know what is. That was not part of the case, but it certainly could have bolstered the right of privacy the court found that we have.

    Also, if a fetus is a life, as pro-lifers like to argue, then the thirteenth amendment which bans slavery also prevents the mother from having to be the slave of the fetus.

    These really are nonsense arguments that the anti-abortionists love to make.

    • Replies: @dearieme
  27. By your simple argument the government can’t enslave me by taxation which is in the words of Lincoln, earning bread by the sweat of my brow, and the bondsman (government) eats it.

    Your third amendment argument is quaint, the establishment of law by metaphor.

  28. dearieme says:

    Oh come off it. It was one of those absurd decisions that leave me thinking that the members of SCOTUS don’t want to be shunned at dinner parties. If the drafters of the Constitution had wanted to invent a right to privacy they’d have said so. They didn’t.

  29. @Dr. Robert Morgan

    Since race differences cause strife, governments want to eliminate them. Genetic engineering will provide much more effective tools for doing this than leaving it to the chance results of long term race mixing.

    This is ridiculously optimistic! Most governments, not all admittedly, try to divide and rule their working classes. Keeping the proles busy fighting each other means that they have little time, thought or energy to spare for their real oppressors, the ruling class.

  30. “Their is no cure for stupidity”. While that may be true today, it seems unlikely that it cannot be “crisped” out of the genome in the near future. What would that do to human society? Maybe, even more importantly, it will probably soon be possible to remove genes for psychopathy and sociopathy. Let’s hope we don’t all die of extreme weather before we can find out what that means!

  31. foolisholdman: “This is ridiculously optimistic! Most governments, not all admittedly, try to divide and rule their working classes. Keeping the proles busy fighting each other means that they have little time, thought or energy to spare for their real oppressors, the ruling class.”

    The idea that human beings would naturally exist in a state of universal brotherhood, and peace would rule the world were it not for “hostile elites” always trying to set every at each others’ throats, is of course an easy sell in societies shaped by Christianity. Karl Marx used it to great effect. The problem is, it doesn’t happen to be true. Darwin’s view of life as eternal struggle of all against all is the truth, not dreams born of religion.

    • Replies: @Factorize
  32. Factorize says:
    @Dr. Robert Morgan

    My impression is that the core supporters of Marxism are those who have fallen from the higher stratas and are horrified at the meager selection of fine French wine available to them in their new socioeconomic station. They are the regressors to the mean: a near statistical certainty given the extremely polygenic architecture of human intelligence.

    Being middle class is really not so bad, or at least you can get used to it. Yet, eviction from paradise and confinement in the heartland would likely seem unbearable. I think we on should feel their pain and take up a collection to help those who through no fault of their own can no longer afford those necessities of civilized existence to which they had grown accustomed.

  33. What is technologically impossible today is done with difficulty tomorrow, easily the da after, and appears in chemistry sets for fourth-graders the next week. If China came up with a reasonably safe, easy way of raising IQ by thirty points, does anyone think there would be any way of stopping it in the US? Would there be a brain race? You know, national security.

  34. Fred V. Reed: “If China came up with a reasonably safe, easy way of raising IQ by thirty points, does anyone think there would be any way of stopping it in the US? ”

    I don’t think so. Other countries would have to follow suit. They’d have no choice.

    Interestingly enough, gains of 15 points or so are already possible using embryo selection.

    China has gotten into embryo selection in a big way, though supposedly not for intelligence … yet.

    Once they do, and it’s shown to work, the IQ arms race will start. It might even start in the West, as a fashion among the rich. If it did, a one standard deviation gain in intelligence would confer a great advantage on their offspring. It would tend to entrench the moneyed classes even further. OTOH, perhaps it could be used to close the IQ gap between blacks and whites. That might be of benefit to society at large, although maybe it might just breed smarter criminals, and be a net loss. As usual, it’s hard to predict all the consequences of a new technological development.

  35. Factorize says:

    The storm is coming. The eye of a psychometric tornado of unimaginable ferocity is heading directly for human civilization.

    Archeological and genetic evidence can demonstrate the novel behaviors and social structures that emerged when human intelligence increased by a mere 1 IQ point in human settlements of vastly reduced scale. Surely, grownups with authority possessing even a slight familiarity with psychometric science must have already concluded that IQ uplift represents an existential threat to humanity. It needs to be recognized that even an increase of 10-30 IQ points in average human intelligence would be of monumental consequence: It would increase the rate of technological progress by 1-3 orders of magnitude.

    Is everyone truly all set to jump on the merry-go-round time machine and experience life in the year 3019? If that were not fun enough, then you could always wait a year to see if the year 4020 were more exhilarating. And of course, if that were still not thought amusing enough, each new generation of enhanced humanoids (possibly for centuries) would increase the rate of progress by another multiplicative factor of 1-3 (or more) orders of magnitude. Whatever comfort that might be derived from contemplating the mysteries of race or class would be lost as we all tried our best to cope with an ever accelerating frenzy of change. The question is no longer whether we can, but whether we should.

    The maelstrom of change unleashed by the Cognitive Singularity could quite reasonably be expected to induce a planetary scale psychosis.

    • Replies: @res
  36. res says:

    Any thoughts on whether the Cognitive Singularity or the AI Singularity will occur first?

  37. Factorize says:

    res, this is a slow pitch over the plate: The AI Singularity is expected in the 2045 time frame, while achieving full Cognitive Singularity (i.e., human IQ uplift) is possibly somewhat beyond even 2050. A realistic scenario is that the initial ramp up of IQ uplift (which is probably already underway) will advance the arrival of artificial general intelligence perhaps to 2040. However, once the sociopolitical machinery recognizes the threat of change (such as IQ uplift), countermeasures are begun to postpone the future from arriving, sometimes permanently.

    Nonetheless, my mind inevitably drifts back to contemplate the Cognitive Singularity. von Neumann’s intellect was described as fully awake in comparison to all others who were considered asleep. How will we cope with a world filled with the fully awake?

    Without question this has to be the most exciting moment in the history of the universe. We are awaiting the time when the entire genetically enhanced intellectual potential of humanity is turned on, powered up, and unleashed. What will such a mind force discover that has been right before our eyes but remained unrecognized? Imagine growing up in a world where instead of a brief instant of mental clarity during your high school graduation your entire life was as alive! Time to start the countdown for the liftoff of human potential!

  38. Factorize says:

    Very exciting! UKBB GWAS has found hundreds of SNPs related to executive function, which while being a somewhat independent concept to IQ is of central importance to many forms of psychopathology. I had understood g as a largely single dimension measure of intelligence, though with this research I might shift my understanding to include more of a slightly blurrier 2-dimensional construct of pure intelligence and executive functioning as without adequate executive functioning one might question whether “intelligent behavior” could even be possible. It is tremendously exciting that such a diverse range of psychological illnesses are related to executive functioning and that perhaps parents might select embryos based on the PGS for this trait: Such selection might create children free of mental illness and with enhanced IQ.

  39. Factorize says:

    “The storm is coming. The eye of a psychometric tornado of unimaginable ferocity is heading directly for human civilization.”

    That storm apparently is now much closer to shore than I appreciated 2 weeks ago. infoproc is reporting that a 5 million person GWAS is in preparation in the UK. I have been musing lately that perhaps we could plead with the UK to move up the UKBB to 750K or 1M (if we were persistent): 5 million was not even in the playbook. 5 million!!! This pushes us decisively through the phase transition and realistically would place inside of the time horizon of the Cognitive Singularity Event.

    The UK continues to be the only nation showing any obvious leadership on the Cognitive Singularity. Given that this is more a pre-news announcement perhaps it will serve as a final wake-up call to everyone that the future is moving at warp speed on an intercept course with humanity; a United Nations type science effort should be organized, along the lines of the Human Genome Project in order to clearly signal that the profound implications of what is being contemplated needs to be put in clear mental view of all of humanity.

    The science necessary for genotyping/sequencing 5 million people is already well established. For me what will be even more interesting is the ethical/group psychotherapy component related to this project. The Nature Genetics article from last July revealed 250 points of EA. If the UKBB 5M /UN Humanity Project reported 1000 points of IQ, then there would be valid grounds for people to become concerned (if not alarmed).

    If we could all somehow move past IQ denialism, accept that people are different yet possess equal inherent humanity, then we could start to feel better (instead of bad) about the journey towards Cognitive Singularity. How close to the precipice of ruin will humanity allow itself to go all in the name of blocking out unsettling ideas from genetics? It does not seem unreasonable to speculate that the UK’s ongoing global leadership on genetics directly relates to its early history of confronting the difficult topics arising from genetics rather than ignoring them. The UK has developed a clear culture of intellectual curiosity about genetics that has put it at the forefront of moving the Cognitive Singularity to reality.

    • Replies: @res
  40. Factorize says:

    Considering that the approaching storm will be of our own making, it is not entirely unreasonable that controls should be placed upon how our future will unfold. Given the profound consequences that will ensue from moving through the genetic phase boundary and revealing the entire genetic architecture of human IQ, legal barriers need to be enshrined into international law. The unilateral opening of the Pandora’s Box of genetics should be illegal. The consent of Humanity needs to obtained before the genetic unlock leads us to the Cognitive Singularity.

  41. res says:

    infoproc is reporting that a 5 million person GWAS is in preparation in the UK.

    Thanks for highlighting that. I read the post, but somehow skimmed over that comment.

    I recently participated in a meeting at No 10 Downing Street in the UK, to plan a project which will genotype 5 million individuals through their National Healthcare System.

    An indicator that the NHS is serious about this is that they are hiring for the project (posted yesterday).

    Genomics England has been asked to prepare a plan for up to 5 million genomic tests over the next 5 years.

  42. Factorize says:

    res, thank you for all the close reading that you do on this blog. I read that wealth article quite closely and I feel that I understood what conclusions the authors were asserting, though your analysis certainly has me questioning whether those conclusions actually follow from their dataset. I am surprised that even highly respected journals such as Intelligence could let the concerns that you have mentioned past their editing process. It would seem to me that when one is discussing extremely contentious topics such as intelligence that one needs to ensure that everything is done to a very high standard. There is peer review and then there is res review!

    Such close reading apparently will be necessary to keep us informed about the GWASes leading to the Cognitive Singularity. I honestly had not heard a word about the 5M plan until the infoproc post. With that post I had been very concerned that the note in fine print towards the bottom that you highlighted was the entire public disclosure that had been made. Would they really be that untransparent about essentially entirely unlocking the human genome? Embarrassingly, I actually thought the answer might have been “YES!”.

    Yet, of course that is completely incorrect: Democracies do not work like that. The story was widely circulated last October that Genomics England intended for 5M genomes in 5 years. {One might have thought that the UKBB would be the logical goto for such a project.} Somehow the news did not reach us. More oddly, when I asked about this on the blog one month ago (see post #9 above) indirectly to the world’s intelligence experts at ISIR, the thread reply (#20) was:

    “I discussed this with researchers at the conference. Getting the number up to 1.7 million would be very time consuming, though the benefit is that it would cast more light on the evolution of intelligence. Personally, I think it would be a very worthwhile effort, but the researchers have to make their decision.”

    They were unaware as well? In fairness, the 5M GWAS might be argued, given the sample envisioned (disabled etc, perhaps without cognitive testing etc.), not an IQ GWAS. Even still we know that there are so many correlated variables (Educational Attainment, income, etc.), that extracting a cognitive signal would not be challenging nor unexpected.

    I had thought that maybe if we were to call for grown-up supervision (the UN?), then perhaps humanity might be saved from itself, though after reading the background on the 5M project it would seem that we are well beyond such redemption. The game plan is to genotype/sequence a range of children’s and other diseases, making a call to deep contemplation (and with it near endless delay) a political non-starter. There are too many people who have too much to gain from this that road blocking is no longer plausible.

    Basically, the yeahs have it. Unlocking the pathology deeply embedded within the human genome will be an overwhelming advance for humanity, not to mention the very extreme cost savings that would ensue. Surprisingly, the UK (as far as I am aware) appears to be the only nation with enough g power to actually recognize the pay-offs and move this forward on the scale needed to date. The US does have the Million Veteran Project (now with 800,000 enrolled) and AllofUS with 210,000, though this is below the 5M which is required for an unlock of IQ etc. Given that there are roughly 50 million genomes out there globally for the asking, if the UK wanted to demonstrate true mastery, they could simply open up their servers and those interested could upload their data. This would be political gold, as it would cost them virtually nothing (return a very large return on their investment) while revealing the genetic origins of a great many traits/illnesses.

    Clearly the horse has left the barn; the Cognitive Singularity is imminent; and I am chewing my fingernails. This is super exciting and scary.

    • Replies: @res
  43. res says:

    though this is below the 5M which is required for an unlock of IQ etc.

    Have you seen anything claiming that? The original estimates were n = 30s for linear CS and 100s for nonlinear CS (s = # SNPs underlying trait). Steve Hsu had estimated 10k SNPs for both height and IQ giving 300k then derated that to 1M in his initial estimate. The number of SNPs appears to be larger for EA (and IQ?), heritability lower, and more measurement noise than for height. But I haven’t seen a revised estimate of sample size needed.

    It is worth noting that the largest quoted sample sizes I have seen are using summary data which reduces the power. I believe the largest aggregate of SNP level data being used is still the UKBB?

    I welcome corrections to any misconceptions above.

  44. Factorize says:

    res, yes, notwithstanding my previous comments concerning the importance of accuracy and close reading I did admittedly merely invent the 5 Meg target. My reasoning was that 5 Meg feels far beyond the level at which the unlock should occur. The previously reported formula which you noted (~30s or ~100s) unlocks IQ at ~1.0 Meg (with MVP, AllofUs and UKBB we are already there), though at 1.0 Meg there is considerably less confidence. The UK 5M in 5 plan gives us a decisive timeline for completely revealing the genetics of intelligence. Now that we have convincingly breached the 1M psychological barrier possibly others will also join the multi-M club.

    • Replies: @res
  45. res says:

    Thanks for replying. I wonder why the NHS chose 5M then. Just a convenient round number? It does seem large enough to give power to resolve many traits given sufficiently good phenotypic information.

  46. Factorize says:

    rest, or as Dr. Thompson now refers to you “res” (though as a sign of respect I prefer Mr. res, I believe you have earned this honorary title for your close readings and concise posts, no doubt such distinctions would be g loaded, distinctions which the many posters who have hurled uncalled for ad hominems in your direction are conspicuously lacking).

    Thank you for circling back to the 5M UK plan! The UK has been making a great many shrewd moves in the genetic space. From the g perspective, it seems that from fairly modest initital advantages Darwin, Galton, Spearman, Brave New World, etc., UKBB and now 5M N 5, cumulative advantages eventually become spontaneously reinforcing. It is typically not easy to surf the wave when scaling up, though so far so good.

    I think there are probably one or two main drivers that pushed them to 5M. One of them must be the politics involved. ALL the major disease communities must be banging on their door: Breast Cancer, Colorectal Cancer, CAD, Dementia, Diabetes: Everyone! They would all be after a nice GWAS of perhaps 1-2 M. Politically, how do you say No? At some point the gov must have blinked and said OK, ice cream and candy for all!
    I think this is made all the easier when you contemplate the economics involved.

    I can give a personal example to illustrate. A great many members of my family have a variant that causes a fairly serious medical condition, though it is typically not fatal. As a ballpark guess I suspect perhaps there are about 1000 family members who have the variant and possibly another 1000 family members who are worried that they might have the variant but don’t actually carry it. Those who were worried well might follow the standard of care screenings which might cost the health care system $25,000 to do futile screenings. I have done an exome scan and I learned that I was not a carrier. No need to waste that $25,000. I can go on line and find those relatives that are carriers and those that are not. Knowing that someone was a carrier would also allow great cost savings as emergency medicine procedures could then be avoided. This one fairly rare variant might cost the global health economy $100 million, yet by optimizing I suspect a great deal of money could be saved, or at least from the UK point of view with the NHS, reallocated.

    It would seem that the accountants are finally becoming aware of how truly large the cost savings probably will be in the age of genetics. It is only when you start to see the familial patterns of disease concentration that you can realize how much of this cost could be removed from the system. Ramping up to 5M seems somewhat flamboyant and perhaps foolhardy until you realize how foolish it would be not to do this. Given this lead others might be similarly emboldened.

    Of course, the great part of all this for the g watchers is that everyone in the 5M has an IQ. IQ tags along no matter what else is involved. If it were a straight question of doing a 2 M IQ/EA GWAS we might have to wait a while. Yet with all these other special interests involved we can simply coast in: not using all available information (IQ/EA etc. info) would probably be seen as squandering scarce tax resources.

  47. Factorize says:

    Genomics England has sequenced 100,000 genomes at a cost of a quarter billion pounds! Yet, I am having a bad feeling about this. There does not seem to be any mention of doing wide scale phenotyping as with the UKBB. Did they really drop a quarter billion and not ask questions such as highest school grade completed etc?

    • Replies: @res
  48. res says:

    High level link to the project:

    They provide a 112 page report:

    Agreed it does not look terribly encouraging for things like IQ/education. This chapter starting on page 29 seems relevant: 4 Opportunities to extend beyond the primary phenotypes

    Figures 3 and 4 on pages 26 and 28 give an interesting look at sample sizes required for different cases.

    I did not look at much beyond that in the report. If you do and see anything interesting please post.

  49. Factorize says:

    res, it looks like the 100K Genomes descended from the UK10K. Remember that one? It was about 10 years ago. That was the time before the wave of polygenics had reached shore. 100K is more focused on cancer and rare diseases. It is somewhat difficult to imagine, though from what I can see on their website the mega polygenic perspective embraced by UKBB has to a large extent not entered the consciousness of Genomics England. They have a much more of a focused clinical perspective devoted to helping patients with substantial health challenges as opposed to phenotyping essentially a typical population sample.

    There is probably at least some connection between GeL and UKBB, they must meet up at conferences or something, though from what I see online it does not appear as though the import of the quarter billion pound investment in the 100K genomes has as yet lead to any neuronal synapses firing and wiring. Basically, there is a rapidly depreciating asset of 250M pounds (possibly 10% per month), and no hint of any application to polygenics. The final release of 100K full genomes was reported in July of this year and their website does not appear to indicate that any research groups have expressed an interest in running the results against the UKBB (e.g., for EA/IQ, height etc.). This is one of the most impressive current global genomics resources that I am aware of at present, though not having the needed phenotypes would clearly be somewhat of a problem. The obvious workaround would be to simply designate the 100K sample as being under the umbrella of UKBB, pending patient consent, if thought necessary, though it is entirely possible that there has been a conscious effort to delink the 100K from the 500K projects.

    The irony here of course is that 100K full genomes for about 10 different types of cancer, childhood illnesses and others probably will not have enough scale to help with any of these problems, especially if they are mainly polygenic. However, if they could take the dataset and combine with the UKBB, then there would be a real treasure trove of information to mine. With EA, 100,000 full genomics would clearly have a large amount of datavalue. We have entered the exponential phase of the genome unlock for EA and other phenotypes so adding 100K genomes should give you in neighborhood of hundreds of new SNPs. This, it should be noted, is, in fact, quite remarkable, as it was not until 2017, only 2 years ago, that there were no replicated genome wide significant SNPs for EA, some thought the entire exercise was folly. So, while the information value for cancer and rare diseases of the dataset might be somewhat limited, the value of this same information given it is near the inflection point of many polygenic human traits including EA and others that are in the 500K sample range of the UKBB is quite large.

    It does not appear as though a full range of phenotypes is being collected in keeping with the UKBB approach, though it is difficult to be entirely sure.

    Here’s the press release for the data release for the full 100K genomes. One might have expected that if they intended to release polygenic phenotypes such as EA etc. that this information would be released in tranches the whole way along.

    This url reports on the ethical and social science research underway. There is no mention of an EA meta analysis with UKBB.

    The best UKBB has reported is 50K exomes.

    The research report on these 50K exomes is impressive. The power of a multi polygenic approach is shown on pdf page 4 where they have a pages of phenotypes linked with the genotypes from the exomes. This is clearly what you want to do, max out the phenotypic output from your investment. Strikingly there was a greater than 10 fold capture of loss of function variants in the sequenced over imputed genotypes. 25% of the imputed values were not found in the actual exomes (page 10) , suggesting that they might simply have been wrong. This information alone might allow for a recomputation of the existing dataset as the false imputations added noise to the signal for example with the EA GWAS. Another 450K exomes are on the conveyor belt and expected within 2 years along with full genomes at some point.

    The 100K full genomes are clearly the shiny coin here, though it is not entirely obvious whether the quarter billion investment will actually show much of a return in relation to a combination with the UKBB if the phenotypes were not to have been collected. res, why didn’t they ask us to help? We’re here to help! We all have a reasonably good idea of who might have the know how to do the analysis etc..

  50. Factorize says:

    res, thank you for all that you do! Your constant fact checking and demand that posters be intellectually honest is very refreshing. There is a constant deluge of distortions and outright falsehoods that appear with disturbing frequency here on unz. I am glad that you are here to push back against it. I do not relish a res take down of my own posts, though watching a master dismantle fuzzy logic is almost magical. Why do so many other posters even bother with their ad hominems? Humanity salutes you res!

    Thank you for pointing out the SD quote from The g Factor. I really wished that AAs might find something that could go in their favor. Yet, an SD of 12, means that 100 IQ goes from 15th to 10th percentile. That is a startling percentage shift.

    I am not fully aware of your thinking about how to go about juggling the admixture IQ calculations, though I felt very uneasy with the simple linear weighting used by other posters.

  51. Factorize says:

    I am working on an assignment for sociology that considers the Big question (the Biggest?) of history, namely the shift that occurred in our economy/society as we transitioned from a pre-industrial to an industrial (during the Industrial Revolution) and then a post-industrial society, along with all the counter-revolutions (such as communism that have occurred along the way). What I am particularly interested in is to provide graphics that demonstrate this process from a psychometric perspective.

    I am quite pleased with Claude le Lorrain’s Paysage pastoral as my artistic selection of the pre-industrial world. A number of psychometric features of interest are present. Specifically, very low density of people and also an economic system that is unable to produce much of a surplus (therefore, no concentration of g, and minimal development of the g that is present). The people apparently lounging around in the middle of the afternoon without information technologies helps to illustrate the social context of the times. The presence of water and the tight focus of the composition are somewhat problematic. Ideally one would want there to be no water as this introduces the potential for g to simply arrive from almost anywhere; some landlocked location possibly with rugged terrain would be better. Any suggestions for a similar work of art which had even more appealing psychometric features would be appreciated. Also any other examples of graphics with strong psychometric features would be welcome.

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