Genetic Enhancement as a Cause Area

post by Galton · 2019-12-25T11:30:09.638Z · score: 93 (40 votes) · EA · GW · 19 comments

Contents

  Basic argument
    The short-term case for genetic enhancement
    The long-term case for genetic enhancement
  Interventions
  Objections and responses
  Conclusion
  Appendix 1: Selected traits with heritability estimates
  Appendix 2: Genetic enhancement for animal welfare
None
19 comments

Originally posted on the EA subreddit.

First, I will present a rough sketch for why genetic enhancement could be a plausible cause X [? · GW]. Then I will list some specific proposals for genetic interventions. I will conclude by responding to objections. If there is interest, I may write more posts on this topic.

Basic argument

There are two main ways to think about genetic enhancement as a potential EA cause area. One perspective is focused on improving short-term human welfare. While reducing “defects” (disabilities, depression, etc.) would be a major focus, this perspective could additionally encompass increasing the frequency of beneficial traits, such as longevity-promoting alleles of the FOXO3 gene. The key idea is that enhancement is performed to increase individual well-being.

The other way of thinking about genetic enhancement, and the one I prefer, takes a long-term view. Changes are made with the far-future of our society in mind. For instance, by drastically increasing IQs, we could put our civilization in a better position to solve complex challenges that exist today or will arise down the line. Other interventions such as increasing empathy and decreasing Dark Triad personality traits could be used to influence the values of our descendents and avert future moral catastrophes.

The short-term case for genetic enhancement

If we want to improve short-term human well-being, we can group most possible interventions into two broad categories:

  1. Improve the quality and duration of life for presently-existing humans.
  2. Change which (and how many) humans will be born in the first place.

The first method is far less philosophically controversial. Everyone agrees that once you’re born, it’s better to live a happy life than a miserable one. On the other hand, when it comes to changing the number and identity of people in existence, we enter the muddy waters of population ethics, fraught with paradoxes and impossibility theorems. For the most basic version of my argument to work, it suffices to assume that when selecting among a fixed number of “potential children” who could be born, we should choose the ones with the highest expected well-being.

I have not yet said anything about genes specifically! Of course, both environment and genetics could be factors when evaluating the expected well-being of potential future humans. However, living environment in general is already subject to more optimization (see next paragraph). It also appears that many traits that contribute to a happy, successful life are highly heritable, including psychological traits (see appendix 1). Further, taking a slightly longer-term view, genetic information is directly passed on for multiple successive generations, while environment is ephemeral. I think a focus on genes is justified.

Going back to the dichotomy of altruistic interventions, the first option is the tack that most effective altruists interested in short-term human welfare have taken. It is also the strategy most popular among do-gooders in general. In comparison, little philanthropic effort is devoted to efforts to (e.g.) decrease the number of children born with severe congenital diseases or to increase the frequency of welfare-promoting alleles in the population. Aside from philanthropy, people in general seek out the best living environment for themselves and their children. On the other hand, although sexual selection does exist, people generally do not explicitly optimize the genetics of their progeny. So it’s clear that improving population genetics is comparatively neglected.

Further, I would argue that genetic enhancement is quite important. A meta-analysis of twin studies found that genetic factors explain 36% of variation in subjective well-being (appendix 1). While environmental conditions obviously play a huge role in well-being as well, the role of genes cannot be understated. If all EA optimization to date has only been targeting 64% of the problem, there might be a lot of low-hanging fruit in that remaining 36%.

It is harder to tell how tractable genetic enhancement is, which depends on the specific type of intervention. I may write a follow-up post exploring this issue in depth if there is sufficient interest.

The long-term case for genetic enhancement

The long-term trajectory of our civilization depends largely on how we navigate the minefield of emerging technologies that will be developed over the next couple of centuries. It likewise depends on the values that our descendents hold.

It seems that increasing IQ and other traits such as affective empathy (see appendix 1) could help humanity to reach a prosperous future. Imagine a world full of people as bright as John von Neumann and as ethical as Gandhi. Wouldn’t such a world be in a vastly better position to avoid existential risks and risks of future suffering than our present Earth?

Bostrom, and others, are fond of saying that we are the “stupidest possible biological species capable of starting a technological civilization.” In many ways, genetic enhancement would change this outlook. If the brightest humans on Earth one day become much wiser than we currently are, then I believe it is highly likely that we could improve the chances of successfully mitigating existential risk.

Consider the case of aligning an artificial intelligence. One model of AI development is that it is a constant race between capabilities gained by factors which provide virtually no safety guarantees, such as increasing hardware capacity, and capabilities gained by a principled understanding of AI design, such as the presentation of causality provided by Judea Pearl. MIRI believes that if we have a principled understanding of advanced AI design before we can build it via stupid means, like simulating evolution, then our chances of aligning such AI are increased dramatically.

In order to gain the upper hand in this race for technological capabilities, we could leverage genetic enhancement to maintain a favorable balance in differential technological development. For instance, progress in hardware is arguably bottlenecked by economic demand, and would not be significantly accelerated by the advent of a hundred John von Neumann level scientists. However, deep insights into the nature of intelligence are the type of thing we should expect if we have a highly competent core group of humans working on the problem.

Ensuring that this highly skilled group of people comes into existence would be much easier to accomplish than the widespread adoption of genetic enhancement implied by the short-term view I presented above. Therefore, it is likely more tractable. Still, selecting embryos for intelligence is highly controversial, and would not be something that most ethics panels would currently approve of. 

In the long term, I believe selecting embryos for favorable traits will happen anyway, regardless of ethical qualms, because once the technology has been demonstrated, countries unwilling to adopt it will risk falling far behind. EAs can therefore do research to track attitudes, and find the right time to begin implementing the strategy outlined above.

Interventions

I have explained why genetic enhancement is an area worth considering, but what can effective altruists actually do to advance the cause? I will now list a few promising, non-coercive forms of genetic enhancement. For each of the following items, EA work could focus on advocacy, research, or technical implementation.

I would highly recommend Gwern’s article on “Embryo selection for intelligence” for a detailed comparison of the feasibility and effectiveness of several different genetic interventions. (Although the title refers to intelligence, the analysis applies equally well to other genetic traits.)

Incentive-based genetic enhancement: We might consider programs that pay for people with desirable traits to reproduce. For example, we could provide high pay to quality sperm and egg donors based on their genetic profiles. We can also leverage recent research in genetics that predicts success based on one’s genetic profile, and pursue further research along these lines. This will help us make the case for incentive-based genetic enhancement, and will provide an effective means to discover high-quality donors.

Embryo selection: First performed in 1990, preimplantation genetic diagnosis (PGD) is a process by which a handful of eggs fertilized via IVF are screened for genetic diseases prior to being implanted in utero. The screening has traditionally been done using FISH (to detect chromosomal abnormalities like Down’s syndrome) or PCR (to diagnose monogenic disorders like sickle-cell anemia). Of the screened embryos, the healthiest one is implanted. There are several different potential variations of the procedure. As would be expected:

Germline gene engineering: There is a lot of hype surrounding the idea of using CRISPR to modify embryos. As many of you know, it’s already been done. While CRISPR does have a great potential to e.g. treat monogenic diseases, Gwern doesn’t think it will produce enormous effects like future versions of embryo selection could. This is partially because genetic studies are not good at isolating which specific single nucleotide polymorphisms are causally responsible for a trait. If we modify a gene which is merely correlated with the trait we are trying to augment, it may be ineffective or possibly even backfire. Moreover, if we want to edit polygenic traits, many individual edits would be required, but currently CRISPR can only be used to make ~5 edits reliably. On the bright side, CRISPR would allow us to increase the frequency of rare beneficial alleles and even create novel “mutations” that we hypothesize to be beneficial (the latter, though, is very risky and wouldn’t pass an ethics board).

Iterated embryo selection: This is a hypothetical technology that could be used to exert a great degree of control over the genome. It involves collecting stem cells from different donors, differentiating these cells into sperm and eggs, and then allowing the gametes to fertilize each other. The zygotes with the most desirable genomes would be differentiated back into sperm and eggs, and the rest discarded. The process can be repeated for several iterations, “compressing multiple generations of selection into a few years or less.” Gwern is quite optimistic about the potential of this technology, expecting it to increase IQ by multiple standard deviations in one generation.

Genome synthesis: This refers to creating a completely new genome from scratch. This procedure would allow the greatest degree of control, and Gwern is quite optimistic about it, but there are several technical challenges that would need to be overcome for implementation.

In general, I think there is high value in having EAs enter government and work on shaping relevant regulations in a more positive direction. It’s additionally possible that conducting more rigorous genetic studies would be useful, but it’s not clear how EA can have a large counterfactual impact there, because academia and the genetic profiling industry are already working on the issue.

Objections and responses

What if increasing these supposedly positive traits results in negative consequences?

It’s important to avoid status quo bias. To quote Bostrom and Ord:

Reversal Test: When a proposal to change a certain parameter is thought to have bad overall consequences, consider a change to the same parameter in the opposite direction. If this is also thought to have bad overall consequences, then the onus is on those who reach these conclusions to explain why our position cannot be improved through changes to this parameter. If they are unable to do so, then we have reason to suspect that they suffer from status quo bias.

But we can give an explanation: evolution! Doesn’t natural selection already work in favor of desirable traits? Isn’t it hubris to think we know better than nature?

Bostrom and Ord give four reasons why this argument is dubious:

  1. The environment of our evolutionary ancestors is different in many ways from our modern world. It’s possible that what is beneficial today was an evolutionary disadvantage for our ancestors, or vice versa.
  2. There may have been trade-offs in the past that are no longer relevant. For instance, we no longer have to worry so much about large brains imposing high metabolic costs, because food is widely available.
  3. Evolution is a blind process, and it’s possible it just never happened to stumble onto the correct combination of genes.
  4. What we care about is not the same as evolutionary fitness. Evolution doesn’t optimize for happiness. The ability to rape and plunder might increase genetic fitness, but we don’t consider them good. Likewise, there could be traits which humans value but that hurt fitness.

Genetic enhancement technology would only be available to the rich. It would greatly increase inequality.

I would like to point out that genetic enhancement is not necessarily a zero-sum game. Sure, there are some genetic traits that are almost exclusively positional goods, i.e. they benefit one person by increasing their status over others. Examples might include physical attractiveness or height. On the other hand, many other characteristics such as health, well-being, and intelligence are considered good in and of themselves. We should focus on the latter.

The enhancement of economically advantageous traits such as intelligence would grow the overall pie of the economy, which we could then redistribute more equitably. Then we’re back to standard political debates about how to set the marginal tax rate.

While it is quite probable that the wealthy would have earlier access to reproductive technology, the price would eventually drop to the point where it could be made available to anyone. If necessary, governments could provide social security benefits to subsidize access for the poor.

One way of alleviating the harm due to inequality is by advocating a tax on innate, unearned qualities, such as favorable genetics and inheritance. I believe that these policies will be popular once the technology comes up on the horizon, and will likely play a large role in mitigating the worst risks of inequality.

Genetic enhancement is too taboo for advocacy to make headway.

I see a few reasons for optimism. First of all, surveys indicate significant support for genetic enhancement and similar ideas. A Pew Research poll found that a majority of Americans would support using gene editing on embryos to treat diseases, although only 20% supported using the same technique to increase IQ. Furthermore, when push comes to shove, 90% of fetuses diagnosed with Down syndrome are aborted.

The bottom line is that genetic enhancement isn’t too far out of the Overton window for advocacy to be futile. At the same time, it’s not so universally accepted that we can assume highly effective enhancement will happen before artificial intelligence arrives. It’s in the perfect zone where a concerted effort on the part of EA advocates could make a difference, either by shifting the development timelines or by influencing policies and norms surrounding its use.

AI timelines are too short for genetic enhancement to have any impact

AI timelines are quite uncertain. According to a survey of AI researchers, the median estimate for the arrival date of “high-level machine intelligence,” defined as AI capable of exceeding humans at all tasks, is 40–50 years away, which would allow for one or two intermediate generations. On the other hand, the 75th percentile date is more than 100 years away. Personally, I’m skeptical of the reliability of these estimates, and I recommend to take them with a grain of salt.

In any case, Bostrom and Shulman have argued that even a single generation of iterated embryo selection for intelligence, limited to a small proportion of the population, could have a massive impact on society. The same goes for genome synthesis and advanced forms of “one-shot” embryo selection. There is likely substantial room for impact in the median scenario.

Genetic enhancement would greatly decrease genetic diversity, leaving us more vulnerable to pandemics or other unforeseen disasters.

While this is technically true, I’m not too worried about it personally. The marginal risk increase seems small enough that the benefits of genetic enhancement dwarf it. It should be noted that this objection is strongest in scenarios where enhancement is highly widespread and where technology enables large jumps in one or two generations.

Selecting for high IQ would make the world more vulnerable to agential risks (e.g., lone wolf extremists building nukes in their backyard)

(Relevant background reading: Torres, Bostrom)
While a society composed of high IQ individuals would indeed be more likely to contain individuals capable of building WMDs in their backyard, such a society would also have smarter control and surveillance methods for preventing acts of terror. Moreover, intelligent people tend to commit less crime. But even if we assume that this one specific risk would increase, it still seems likely to me that total existential risk would decrease, for the reasons I mentioned in the “long-term” argument.

We risk creating a race of enhanced humans who won’t care about (or will subjugate) the rest of us.

First of all, this concern is usually based on science fiction like Gattaca. I would warn that generalizing from fictional evidence is not a reliable way to arrive at true beliefs.

Beyond that, research shows that intelligent people are more altruistic and less discriminatory rather than the opposite.

Even assuming the above research is false, from a principled perspective, there seems to be no compelling moral reason to keep our gene pool the way it is. It is typically assumed that creating a class of people who are highly cognitively capable would be unfair to the rest of us.

However, disparities in cognitive ability already exist via natural means. To the extent that these natural disparities are acceptable, then inducing further changes doesn’t fundamentally “change the rules of the game.” In fact, these technologies could actually level the playing field, if we allowed broad distributed access to them.

Historically, increases in the average intelligence of populations has been overwhelmingly considered a positive thing. The long running Flynn effect has likely contributed to lifting nations out of poverty, achieving the exact opposite effect of the dystopian worries we are often reminded of.

Conclusion

Genetic enhancement is a plausible candidate for a cost-effective cause area. There are both short-term and long-term arguments for the desirability of genetic enhancement, and several different approaches that could be used to improve the gene pool. The field is highly neglected and important, but tractability remains uncertain.

The Centre for Effective Altruism has stated that they believe EA needs to incorporate a variety of different approaches to addressing existential risk. I believe genetic enhancement is a cause area that belongs within the effective altruist portfolio. At the very least, it deserves much more attention at the level of cause prioritization than it has received until now.

Appendix 1: Selected traits with heritability estimates

You can see more at SNPedia.

Neuropsychological disorders

Physical disorders

Important psychological constructs

Also worth pointing out: George Church has a list of single gene variants that have already been shown to have a large effect on human welfare.

Appendix 2: Genetic enhancement for animal welfare

We already have evidence that artificial selection pressure applied by humans can powerfully shape evolution. Look no further than the wide variety of domestic animals and cultivated plants that owe their unique features to the whims of their breeders. Unfortunately, animals have generally been bred for their utility to humans even when this comes at the expense of their own welfare. Over the past century, livestock breeders have substantially increased productivity through genetic modifications. The same modifications have introduced a plethora of horrific afflictions that affect billions of farm animals every year.

While animal breeding may seem like a cause for despair, it also offers us a potential solution to reduce farm animal suffering. Adam Shriver has argued that we should genetically engineer livestock that have a diminished (ideally eliminated) capacity for suffering. This is a research area with huge potential for impact, although it does have some drawbacks as well. Specifically, we would need to be sure that we were actually reducing the feeling of suffering, and not just the behavioral reaction to the feeling. Furthermore, some ethical theories suggest that it is wrong to exploit and kill animals full stop, even if the animals are not in pain. Finally, reducing pain may hamper efforts to completely end the practice of animal farming, as animal rights “abolitionists” argue. Despite the concerns, I would nonetheless be excited to see more research on this issue.

In recent years, there has been growing moral concern for the suffering that wild animals experience due to natural processes such as disease, parasitism, and Malthusian scarcity. Geneticist Kevin Esvelt, one of the pioneers of CRISPR/Cas9 gene drive technology, has suggested that we may have a moral obligation to use our technological powers for the benefit of wild-animal welfare. For decades, transhumanist philosopher David Pearce has been arguing along similar lines. While these ideas are still extremely speculative, further research on the topic could be valuable.

19 comments

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comment by David_Althaus · 2019-12-25T17:31:01.386Z · score: 15 (9 votes) · EA(p) · GW(p)

Great post!

I've been thinking along similar lines though I put the emphasis on selecting against dark tetrad traits.

I've written a longer Google Doc (which is not quite ready for publication yet). Would you be interested in taking a look?




comment by gwern · 2019-12-26T22:15:09.219Z · score: 14 (5 votes) · EA(p) · GW(p)

How do you plan to deal with the observation that GWASes on personality traits have larger failed, the SNP heritabilities are often near-zero, and that this fits with balancing-selection models of how personality works in humans?

comment by David_Althaus · 2019-12-28T16:28:06.920Z · score: 17 (7 votes) · EA(p) · GW(p)

(Epistemic disclaimer: My understanding of genetics is very limited.)

If additive heritability for all the relevant personality traits was zero, many interventions in this area are pointless, yes.

I might have underestimated this problem but one reason why I haven’t given up on the idea of selecting against “malevolent” traits is that I’ve come across various findings indicating SNP heritabilities of around 10% for relevant personality traits. (See the last section of this comment for a summary of various studies).

SNP heritabilities of ~10% (or even more) for relevant personality traits seem also not implausible on theoretical grounds. If I understand Penke et al. (2007, see Table 1 in particular) correctly, balancing-selection models of personality predict that personality traits should show less additive heritability than, say, cognitive ability, but not (necessarily) zero additive heritability.

Granted, 10% is pretty low, but is it hopelessly low? According to Karavani et al. (2019), a polygenic score for IQ which explains 4% of the variance, would enable an average increase of 3 IQ points (assuming 10 available embryos). I infer from this that a polygenic score which can explain only ~4% of the variance in, say, psychopathy would still enable the reduction of ~ 1/5 of a standard deviation in average psychopathy scores, assuming 10 embryos. Polygenic scores explaining ~10% of the variance might thus enable considerably larger average reductions of ⅓ - ½ of a standard deviation or so (numbers pulled out of my posterior).

Again, ⅓ of a SD might seem underwhelming but, as you emphasize in your essay on embryo selection, small changes in the mean of a normal distribution can have large effects out on the tails, so this could still lead to surprisingly large reductions in the frequency of extreme psychopathy or sadism (~psychopathy scores 2-3 SDs above the norm), even in “normal” IVF embryo selection. When applied in iterated embryo selection (IES), this could result in much stronger effects still.

Again, I could easily be wrong about any of the above.

Will SNP heritability estimates increase with larger sample sizes?

This is at least what Tielbeek et al. (2017) suggest: “Recent GWASs on other complex traits, such as height, body mass index, and schizophrenia, demonstrated that with greater sample sizes, the SNP h2 increases. [...] we suspect that with greater sample sizes and better imputation and coverage of the common and rare allele spectrum, over time, SNP heritability in ASB [antisocial behavior] could approach the family based estimates.”

Higher additive heritability for personality disorders?

Another point that makes me somewhat hopeful is that specific personality disorders seem to show larger additive heritabilities than personality traits. For example, the meta-analysis by Polderman et al. (2015, Table 2) suggests that 93% of all studies on specific personality disorders “are consistent with a model where trait resemblance is solely due to additive genetic variation”. (Of note, for “social values” this fraction is still 63%).

And a lot of the benefits in this area might come from selecting against, say, antisocial or narcissistic personality disorder (sadly, sadistic personality disorder is not a thing anymore but it was included in the appendix of DSM-II).

But it’s been a while since I read the Polderman paper and I’m also a bit confused by how there can be high additive heritability for, say, narcissistic personality disorder but very low additive heritability for narcissism as a trait, so the above might be wrong.

Some interventions in this area don’t require additive heritability

There are also interventions that work, even if additive heritability is zero though they assume that the non-additive genetic variance is at least partly due to dominance and not solely due to epistasis; I think. For example, ensuring that the parents of the first generation of IES embryos score low on dark tetrad traits or influencing the first genome synthesis projects to make their first genomes as similar to those of people scoring low on dark tetrad traits as possible (alongside edits to achieve substantial IQ increases, of course).

Lastly, there are interventions that have nothing to do with genetic enhancement but would benefit from more research on and advocacy for screening against malevolent traits and are thus somewhat related to the above. For example, it seems valuable to develop better measures of malevolent traits, potentially ones that are impossible to game such as neuroimaging techniques. Such measures could then be used in various high-impact settings to. For example, they would enable decision makers to better screen for highly elevated dark tetrad traits in government officials, humans whose brains will be used to create the first ems, and human overseers in AI projects. (Currently, all measures of malevolence seem to be self-report questionnaires or interviews which seem easily gameable by smart psychopaths.)

Is non-additive genetic variance really useless?

(No need to reply to the questions in this section.)

Assume that all of the genetic variance in trait A is due to dominance. Wouldn’t it still be possible to achieve non-zero increases/decreases in trait A via (iterated) embryo selection?

And what about epistasis? Is it just that there are quadrillions of possible combinations of interactions and so you would need astronomical sample sizes to achieve sufficient statistical power after correcting for multiple comparisons?

Some evidence for non-zero SNP heritabilities of relevant personality traits

Table 4 of Sanchez‐Roige et al. (2018) provides a good summary. Below, I focus on studies examining traits that likely correlate with dark tetrad traits, such as agreeableness and conscientiousness.

The UK biobank (N ≈ 290k) estimates SNP heritabilities of around 10% for various personality traits, some of which probably even correlate with psychopathy, such as the items “do you often feel guilty?” and “Do you worry too long after an embarrassing experience?”. (Don’t get me wrong, I’m not saying that we should select against traits that only correlate with psychopathy while being completely fine in themselves, like e.g. not often feeling guilty. I'm just listing these items to support the hypothesis that as long as we can find SNP heritability for them, we can expect to find SNP heritabilities for related traits as well.) Unfortunately, the UK biobank didn’t seem to measure any personality trait apart from neuroticism (estimated SNP heritability: 11%). Also, they usually didn’t even use likert scales, only dichotomous yes/no responses, which might reduce heritability estimates (??).

A GWAS (N = 46,861) by Warrier et al. (2018) found an additive heritability, explained by all the tested SNPs, for the Empathy Quotient of 11%. (The Empathy Quotient contains items like “I get upset if I see people suffering on news programmes” and “I really enjoy caring for other people” and thus probably correlates negatively with dark tetrad traits.)

Verweij et al. (2012) give a SNP heritability of 6.6% for harm avoidance which likely correlates with dark tetrad traits.

Lo et al. (2017) estimate SNP-based heritabilities of 18% for extraversion, 8.5% for agreeableness and 9.6% for conscientiousness (see supplementary table 2). (N = 59,176).

Granted, Power and Pluess (2015) estimate SNP heritability of agreeableness and conscientiousness as 0%. However, their sample size of 5,011 is much smaller than the sample sizes above and they write: “It is worth noting that the large standard errors around the negative findings suggest increased sample size may identify a low but significant level of heritability.”

comment by gwern · 2020-01-13T00:28:20.347Z · score: 4 (3 votes) · EA(p) · GW(p)
“Recent GWASs on other complex traits, such as height, body mass index, and schizophrenia, demonstrated that with greater sample sizes, the SNP h2 increases. [...] we suspect that with greater sample sizes and better imputation and coverage of the common and rare allele spectrum, over time, SNP heritability in ASB [antisocial behavior] could approach the family based estimates.”

I don't know why Tielbeek says that, unless he's confusing SNP heritability with PGS: a SNP heritability estimate is unconnected to sample size. Increasing n will reduce the standard error but assuming you don't have a pathological case like GCTA computations diverging to a boundary of 0, it should not on average either increase or decrease the estimate... Better imputation and/or sequencing more will definitely yield a new, different, larger SNP heritability, but I am really doubtful that it will reach the family-based estimates: using pedigrees in GREML-KIN doesn't reach the family-based Neuroticism estimate, for example, even though it gets IQ close to the IQ lower bound.


For example, the meta-analysis by Polderman et al. (2015, Table 2) suggests that 93% of all studies on specific personality disorders “are consistent with a model where trait resemblance is solely due to additive genetic variation”. (Of note, for “social values” this fraction is still 63%).

Twin analysis can't distinguish between rare and common variants, AFAIK.

The SNP heritabilities I'm referring to are https://en.wikipedia.org/w/index.php?title=Genome-wide_complex_trait_analysis&oldid=871623331#Psychological There's quite low heritabilities across the board, and https://www.biorxiv.org/content/10.1101/106203v2 shows that the family-specific rare variants (which are still additive, just rare) are almost twice as large as the common variants. A common SNP heritability of 10% is still a serious limit, as it upper bounds the PGS which will be available anytime soon, and also hints at very small average effects making it even harder. Actually, 10% is much worse than it seems even if you compare to the quoted IQ's 30%, because personality is easy to measure compared to IQ, and the UKBB has better personality inventories than IQ measures (at least, substantially higher test-retest reliabilities IIRC).

Dominance...And what about epistasis? Is it just that there are quadrillions of possible combinations of interactions and so you would need astronomical sample sizes to achieve sufficient statistical power after correcting for multiple comparisons?

Yes. It is difficult to foresee any path towards cracking a reasonable amount of the epistasis, unless you have faith in neural net magic starting to work when you have millions or tens of millions of genomes, or something. So for the next decade, I'd predict, you can write off any hopes of exploiting epistasis to a degree remotely like we already can additivity. (Epistasis does make it a little harder to plan interventions: do you wind up in local optima? Does the intervention fall apart in the next generation after recombination? etc. But this is minor by comparison to the problem that no one knows what the epistasis is.) I'm less familiar with how well dominance can work.

----

So to summarize: the SNP heritabilities are all strikingly low, often <10%, and pretty much always <20%. These are real estimates and not anomalies driven by sampling error, nor largely deflated by measurement error. The PGSes, accordingly, are often near-zero and have no hits. The affordable increases in sample sizes using common SNP genotyping will push it up to the SNP heritability limit, hopefully; but for perspective, recall that IQ PGSes 2 years ago were *already* up to 11% (Allegrini et al 2018) and still have at least 20% to go, and IQ isn't even that big a GWAS success story (eg height is >40%). The 'huge success' story for personality research is that with another few million samples years and years from now, they can reach where a modestly successful trait was years ago before they hit a hard deadend and will need much more expensive sequencing technology in generally brandnew datasets, at which point the statistical power issues become far more daunting (because rare variants by definition are rare), and other sources of predictive power like epistatic variants will remain inaccessible (barring considerable luck in someone coming up with a method which can actually handle epistasis etc). The value of the possible selection for the foreseeable future will be very small, and is already exceeded by selection on many other traits, which will continue to progress more rapidly, increasing the delta, and making selection on personality traits an ever harder sell to parents since it will largely come at the expense of larger gains on other traits.

Could you select for personality traits? A little bit, yeah. But it's not going to work well compared to things selection does work well for, and it will continue not working well for a long time.

comment by David_Althaus · 2020-01-20T17:02:46.986Z · score: 3 (3 votes) · EA(p) · GW(p)
I don't know why Tielbeek says that, unless he's confusing SNP heritability with PGS: a SNP heritability estimate is unconnected to sample size. Increasing n will reduce the standard error but assuming you don't have a pathological case like GCTA computations diverging to a boundary of 0, it should not on average either increase or decrease the estimate... Better imputation and/or sequencing more will definitely yield a new, different, larger SNP heritability, but I am really doubtful that it will reach the family-based estimates: using pedigrees in GREML-KIN doesn't reach the family-based Neuroticism estimate, for example, even though it gets IQ close to the IQ lower bound.

Thanks, all of that makes sense, agree. I also wondered why SNP heritability estimates should increase with sample size.

To summarize, my sense is the following: Polygenic scores for personality traits will likely increase in the medium future, but are very unlikely to ever predict more than, say, ~25% of variance (and for agreeableness maybe never more than ~15% of variance). Still, there is a non-trivial probability (>15%) that we will be able to predict at least 10% of variance in agreeableness based on DNA alone within 20 years, and more than >50% probability that we can predict at least 5% of variance in agreeableness within 20 years from DNA alone.

Or do you think these predictions are still too optimistic?

https://www.biorxiv.org/content/10.1101/106203v2 shows that the family-specific rare variants (which are still additive, just rare) are almost twice as large as the common variants.

Interesting, thanks.

But couldn’t one still make use of rare variants, especially in genome synthesis? Maybe also in other settings?

The value of the possible selection for the foreseeable future will be very small, and is already exceeded by selection on many other traits, which will continue to progress more rapidly, increasing the delta, and making selection on personality traits an ever harder sell to parents since it will largely come at the expense of larger gains on other traits.

I agree that selecting for IQ will be much easier and more valuable than selecting for personality traits. It could easily be the case that most parents will never select for any personality traits.

However, especially if we consider IES or genome synthesis, even small reductions in dark personality traits—such as extreme sadism—could be very valuable from a long-termist perspective.

For example, assume it’s 2050, IES is feasible and we can predict 5% of the variance in dark traits like psychopathy and sadism based on DNA alone. There are two IES projects: IES project A only selects for IQ (and other obvious traits relating to e.g. health), IES project B selects for IQ and against dark traits, otherwise the two projects are identical. Both projects use 1-in-10 selection, for 10 in vitro generations.

According to my understanding, the resulting average psychopathy and sadism scores of the humans created by project B could be about one SD* lower compared to project A. Granted, the IQ scores would also be lower, but probably by no more than 2 standard deviations (? I don’t know how to calculate this at all, could also be more).

It depends on various normative and empirical views whether this is worth it, but it very well might be: 180+IQ humans with extreme psychopathy or sadism scores might substantially increase all sorts of existential risks, and project A would create almost 17 times** as many such humans compared to project B, all else being equal.

The case for trying to reduce dark traits in humans created via genome synthesis seems even stronger.

One could draw an analogy with AI alignment efforts: Project A has a 2% chance of creating an unaligned AI (2% being the prevalence of humans with psychopathy scores 2 SDs above the norm). Project B has only a 0.1% chance of creating an unaligned AI. Project B is often preferable even if it's more expensive and/or its AI is less powerful.

*See the calculation in my above comment: A PGS explaining 4% of variance in a trait can reduce this trait by 0.2 standard deviations in one generation. This might enable 1 SD (?) in 10 in vitro generations; though I don’t know, maybe one would run out of additive variance long before?

**pnorm(12, mean=10, sd=1, lower.tail=FALSE) / pnorm(12, mean=9, sd=1, lower.tail=FALSE) = 16.85. This defines extreme psychopathy and/or sadism as being 2 SDs or more above the norm, assumes that these traits are normally distributed, and that project B indeed has average scores of 1SD less than project A. (It also assumes IQ means for the two projects are identical, which is not realistic.)

comment by Galton · 2019-12-26T00:10:42.256Z · score: 1 (1 votes) · EA(p) · GW(p)

Yes, I'd love to see it!

comment by David_Althaus · 2019-12-26T16:01:15.546Z · score: 1 (1 votes) · EA(p) · GW(p)

Great! Sent you a PM.

comment by lynettebye · 2019-12-27T17:39:03.738Z · score: 11 (5 votes) · EA(p) · GW(p)

Do you know what the landscape is of people working on this now, and whether any of them are doing it in an EA-ish way?

comment by Larks · 2020-01-05T01:42:48.853Z · score: 7 (4 votes) · EA(p) · GW(p)

I thought this was a very interesting article, but I would question how much counterfactual difference we could expect intervention to make here. My default expectation is that a lot of this is going to happen anyway due to demand from parents. My impression is that IVF and PGS screening both became very commonplace with little explicit policy support for exactly this reason. This doesn't apply to setting external incentives, but does apply to many of the specific technologies you mention.

I also thought this was a little strange:

One way of alleviating the harm due to inequality is by advocating a tax on innate, unearned qualities, such as favorable genetics and inheritance. I believe that these policies will be popular once the technology comes up on the horizon, and will likely play a large role in mitigating the worst risks of inequality.

With genetic enhancement, favourable genetics are (no longer) random - they are the result of a deliberate decision that you are trying to encourage. How many parents would want to curse their child with higher taxes? It seems rather strange that we should start taxing (e.g. discouraging) this good thing precisely at the moment it becomes possible to promote it!

Finally, you might enjoy this article [LW · GW] by Eliezer. One interesting point is that there is something of a collective action problem, because each mutation is probably bad for the individual/family with it but provides useful information for everyone else.

comment by EdoArad (edoarad) · 2019-12-25T12:13:22.337Z · score: 6 (4 votes) · EA(p) · GW(p)

Thanks for this post! Without knowing much, genetic enhancement feels to me exactly like the kind of cause we should look into deeply.

The paper of Shulman and Bostrom is from 2013, and focused on policy. I guess that advances in biological techniques and the "crispr babies" story has decision makers take it more seriously. Is there anything close to an accepted global ethical conventions around it? Or major conferences/initiatives that do good work on the policy side?

Also, how mature is the concept of Iterated Embryo Selection?

comment by gwern · 2019-12-26T21:05:15.823Z · score: 16 (6 votes) · EA(p) · GW(p)
Also, how mature is the concept of Iterated Embryo Selection?

The concept itself dates back to 1998 , as far as I can tell, based on similar ideas dating back at least a decade before that.

There has been enormous progress in various parts of the hypothetical process, like just yesterday Tian et al 2019 reported taking ovarian cells (not eggs) and converting them into mouse eggs and fertilizing and yielding live healthy fertile mice. This is a big step towards 'massive embryo selection' (do 1 egg harvesting cycle, create hundreds or thousands of eggs from the collected egg+non-egg cells, fertilize, and select, yielding >1SD gains), and of course, the more control you have over gametogenesis in general, the closer you are to a full IES process.

The animal geneticists are excited about IES, to the point of reinventing it like 3 times over the past few years, and are actively discussing implementing it for cattle. Humans, of course, who knows? But I wouldn't want to bet against IES happening during the 2020s for some species, at least in lab demonstrations. (For comparison, think about the state of the art for GWASes, editing, gametogenesis, and cloning in 2010 vs now.)

So I would phrase it as, much more obscure an idea than it deserves to be, with lots of challenging technical & engineering work still to be done, but well within current foreseeability; and will likely happen quite soon on the scale of 1-3 decades (being highly conservative) even without any particularly focused research efforts or 'Manhattan projects', because the required technologies are either far too useful in general (stem cell creation, gametogenesis), or have constituencies who want it a lot (animal breeders/geneticists, wealthy gay couples).

comment by meerpirat · 2019-12-29T18:24:57.650Z · score: 3 (3 votes) · EA(p) · GW(p)

Thank you for writing this, I find the idea very interesting.

Your argument against worrying about negative consequences didn't pick me up.

What if increasing these supposedly positive traits results in negative consequences?
It’s important to avoid status quo bias. To quote Bostrom and Ord:
"Reversal Test: When a proposal to change a certain parameter is thought to have bad overall consequences, consider a change to the same parameter in the opposite direction. If this is also thought to have bad overall consequences, then the onus is on those who reach these conclusions to explain why our position cannot be improved through changes to this parameter. If they are unable to do so, then we have reason to suspect that they suffer from status quo bias."

I take issue with the Reversal test because it seems very difficult to have a realistic picture of a world where a parameter like IQ is increased or decreased significantly. Therefore, the "status quo bias" might be a reasonable attitude if we have very little understanding of the dynamics of our system and there is little chance of reversing the intervention (e.g. you mention a slippery slope dynamic where once genetic enhancement is used everyone will more or less have to use it).

Imagine that I currently feel more or less content with the broad trends of humanity and would like to be very careful before supporting profound interventions like widespread availability of genetic enhancement.

comment by xccf · 2020-01-02T21:21:42.274Z · score: 2 (4 votes) · EA(p) · GW(p)

I think a good way to explore potential downsides of this proposal, and also potentially reduce the taboo around genetic enhancement, would be to steelman the concerns of people who are reflexively opposed to it.

For example, how likely is it that talking about genes more (e.g. the genetic basis of intelligence) will cause people to associate moral value with genes or feel contempt for those are genetically unlucky? You could do psychology experiments where you tell participants that X% of variation in some trait is genetic and see how that affects their attitude towards people without that trait. Does the framing matter? Do some framings cause dehumanization and others cause compassion?

You could also look at historical case studies and try to tease apart causality: Did the progressive eugenics movement amplify the racism of that time period or just reflect it? Did Hitler become interested in genes because he was racist, or did he become racist because he was interested in genes?

You're both looking for potential downsides to this kind of advocacy, and also looking for framings which will minimize potential downsides while framing genetic enhancement in a way that broadens support among those who might consider it taboo. For example, subsidize it as a way to decrease inequality. Genetic inequality is arguably more unfair than any other kind!

Finally, regarding the We risk creating a race of enhanced humans who won’t care about (or will subjugate) the rest of us. point, one idea for mitigating this is to introduce genetic enhancement soon, before we are very good at it, so there is a gradual increase in the level of e.g. intelligence instead of a sudden one. That could decrease tribalism, since instead of there being an "ultra-enhanced" tribe and a non-enhanced tribe with nothing in between, there are many people with many different levels of enhancement in the middle to keep the peace and foster compassion and understanding.

comment by kewlcats · 2020-07-07T15:32:16.019Z · score: 1 (1 votes) · EA(p) · GW(p)

I'm wondering if there are any updates here?

A plausible next step seems to be quantifying the counterfactual impact that EA could have, and comparing that to other cause areas.

China seems to be doing a lot of secretive research in this domain.

IMHO, I think this is an excellent cause area, and would be interested in brainstorming further steps with like-minded folks.

comment by MichaelA · 2020-05-29T05:56:31.438Z · score: 1 (1 votes) · EA(p) · GW(p)

Interesting post!

For instance, progress in hardware is arguably bottlenecked by economic demand, and would not be significantly accelerated by the advent of a hundred John von Neumann level scientists. However, deep insights into the nature of intelligence are the type of thing we should expect if we have a highly competent core group of humans working on the problem.

I'm not sure I understand the reasoning here. Does it not largely depend on what those hundred JVN-level scientists end up using their talents for? I.e., if they all happened to focus on making breakdowns in hardware (or in related areas, perhaps more theoretical/fundamental ones), wouldn't that mean that hardware would be considerably advanced? Or couldn't it be that they all focus on areas fairly unrelated to either hardware or the nature of intelligence, leaving us in roughly the same position we were in before?

(These questions are more sincere than rhetorical; I may just be missing something.)

comment by cole_haus · 2020-01-03T02:45:32.425Z · score: 1 (1 votes) · EA(p) · GW(p)

I think an interesting target for genetic enhancement is moral enhancement--both because it plausibly seems quite valuable and because it seems to avoid many of the most obvious objections to more stereotypical genetic enhancement. There's a fair bit of existing work in the area and Moral Neuroenhancement is a good (in my amateur opinion) introduction.

(Also, I think Modelling the social dynamics of moral enhancement: social strategies sold over-the-counter and the stability of society is a fun/interesting paper on the topic. (One of the authors is Sandberg of FHI.))

comment by eFish · 2019-12-26T20:35:55.409Z · score: 1 (1 votes) · EA(p) · GW(p)

Thanks for bringing up the topic!

In the long term, I believe selecting embryos for favorable traits will happen anyway, regardless of ethical qualms, because once the technology has been demonstrated, countries unwilling to adopt it will risk falling far behind.

Another reason how selecting embryos may become a norm is that, as the technology matures, parents will eventually have a choice to have at least a slightly higher hedonic set-point for their children. Why would they choose not to have happier children? Presumably, more positive children are more fun to raise and are expected to be successful in life. So, other time, psychological pain may be genetically eliminated / reduced. See perhaps this line of argument in David Pearce’s The Reproductive Revolution.

Also, “short-term” improvement in well-being may be considered the long-termist’s goal as WMD, which are expected to be much more available in future, are arguably less likely to be used by “life lovers”.

comment by ishi · 2019-12-25T14:33:19.185Z · score: 1 (5 votes) · EA(p) · GW(p)

Though I find alot of EA writing to be basically a different dialect (eg 'Overton window...') and difficult to read this article seems fairly well written and complete (though often its easy to miss some important issues for complex topics). Theoretical genetics and evolutionary theory are among my pet interests though I am not employed in the field.

But i basically support the precautionary principal so I would not 'cause prioritize' genetic enhancement at present any more than I think going to and colonizing Mars or developing a 'superintelligence' is a priority. I view these as causes worth thinking about and perhaps working on---and many people are already doing that---but they do not take priority over other causes in my view. If EA is about 'doing the greatest good' I would place many of my bets on other causes. (Also given the intricacies of genetics, its very possible alot of research and money can be wasted on things that basically do not turn out to be effective---they just become big money sinks for people with vested interests in their narrow interests.)

In fact i would say learning and studying (or doing research in) theoretical genetics and evolution , and also getting many more people in the population interested in practicing that to be a greater priority. (This may be partly my bias--I'm not interested in policy work promoting this cause (i don't like most policy work, unless its more like doing reseach) and I don't want to work in genetic or other labs.)

I similarily don't see promoting new advanced weapons developement in Federal agencies as a priority because many of the people who would decide how to use them i don't have confidence in--their judgement or competency.

Despite my views, I know alot of people will prioritize this cause and already do, and crowd out resourcces for what i think are more cost effective projects.

(The link to the paper blog on how more intelligent people tend to be more tolerant/less discriminitary is interestng though i think issue is also very complex---and I might dispute it because 'underspecified' (there are lots of forms of discriminatory attitudes ). However the author of that blog does have another one on another cause 'Universal Basic income' --his paper is very interesting , and UBI as a cause I think may rank above genetic enhancement---but is an equally complex issue (i.e. just handing out money could be as disastrous as giving geneticists huge budgets to design the future).




comment by eFish · 2019-12-27T14:37:02.670Z · score: 1 (1 votes) · EA(p) · GW(p)

[...] UBI as a cause I think may rank above genetic enhancement [...]

I would counter that genetic enhancement would be the only cause that could address the root problem - the biology of suffering itself. Environmental interventions, on the other hand, are ultimately limited by the "hedonic" treadmill effect (that is not to say, of course, that the worst cases like factory farming and extreme poverty should not be solved ASAP).