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Comment by technotony | Hacker News Reader

This has several big implications:

1. Women will soon not need to go through the painful (and expensive) process of freezing eggs. (soon being when this is shown to be safe and equivalent to existing eggs). This will enable older women to have kids and solve some reproductive issues.

2. This will lead to a massive rise in availability of human eggs for scientific research, accelerating many fields. Lack of availability of eggs (as they get prioritized for other uses) restricts things like embryo research and other genetic analysis of human germline

3. Potentially this could lead to gay couples being able to have genetically descended children (obviously male couples here, but similar work on sperm is being done that could potentially enable lesbian couples to have kids too). This can be done as skin cells can be turned into pluripotent stem cells, and then maybe into the eggs (still some missing pieces in this process)

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> This will lead to a massive rise in availability of human eggs for scientific research, accelerating many fields.

It will also mean a massive rise in the availability of human eggs for turning into embryos, which in turn will mean the ability to be much more selective about which embryos to to implant during IVF.

Currently egg harvesting is such an arduous process that embryos can only realistically be selected for viability and a handful of generally fatal diseases. When you are choosing 1 out of 7-10 embryos, you can't be all that picky. But between having access to hundreds of eggs, sperm obviously not being an issue, the ever decreasing cost of genomic sequencing, and the ever increasing knowledge of how specific genes relate to traits, parents undergoing IFV could start to apply many selection criteria. That wouldn't be genetic engineering in the classic sense, nothing would be available that wasn't in one of the parent's DNA, but it would get a lot of the way there.

Edit: If I was going to be beaten to the punch by anyone on this subject, I'm happy it was gwern.

And one day soon children conceived the 'natural' way will be at a disadvantage. Reminds me of Gattaca...

it's happening already

No it's not. I don't know of any non-naturally born people who have an advantage. Currently, people born via IVF are more likely to be born prematurely and with increased risks of mental and physical problems.

We may be there soon, but we're definitely not there yet.

> Currently, people born via IVF are more likely to be born prematurely and with increased risks of mental and physical problems.

Cite? The research I found on this indicated that IVF children were exactly average, and IVF with use of sperm donors actually had considerably lower risk of birth defects.

I can second this from a non-statistical point of view. IVF is pretty common in my relative circle and I do not find the kids to have any sort of mental/physical issues

The research is still uncertain, and it may also depend on whether or not you do ICSI. When you do IVF though you need notarized signatures from both partners next to a dozen or so possible categories of birth defects where the child may have an increased risk, e.g.:

https://www.ncbi.nlm.nih.gov/pubmed/29164811

If you're curious you can probably just stop by your local teaching hospital and ask for a copy of the 50+ page contract with all the informed consent details.

If things like congenital heart defects are a real risk (especially a doubling), it should show up very easily in mortality and other hard endpoints. As it is, that just sounds like another anomaly from observational data. (Reading that one in particular, none of the studies use any kind of strong controlling for parental factors, to mention the most obvious problem with trying to infer causation of harm in IVF.)

> If you're curious you can probably just stop by your local teaching hospital and ask for a copy of the 50+ page contract with all the informed consent details.

What a contract says is of little scientific value, unless one is studying tort law and the finer details of butt-covering.

As for the mortality issue, the oldest IVF baby is currently something like 38. And given that it didn’t become common until even later, we’re not going to have that data for several decades.

> What a contract says is of little scientific value, unless one is studying tort law and the finer details of butt-covering.

They have actual statistics though if not references to the primary sources, so that was more the reasoning.

> As for the mortality issue, the oldest IVF baby is currently something like 38.

My point is that a congenital heart defect is something that should strike early, especially in childhood (and that's one of the usual ways to find out about it, kids dropping dead for no good reason, like after being lightly hit in a football game). If a doubling of defects can be detected, so too should a doubling of heart-related mortality. There's on the order of a million IVF kids annually in the USA alone; it's not possible for that to have gone unnoticed. So either their risk is the same as their non-IVF peers and such defects are just common among older mothers, or the defects are not actually serious (pace studies showing that things like cancers or spinal anomalies are common among healthy people, or, more IVF related, that many embryos discarded for chromosomal abnormalities turn out, when implanted, to work perfectly fine because the abnormal cells die or the embryo otherwise recovers during development).

> it's not possible for that to have gone unnoticed

Keep in mind that 93% of heart defects are detectable via an echocardiogram around week 24 of pregnancy. So I would imagine that in most cases where the heart defect is fixable then it's repaired, or else if it's not fixable but also not serious then the kid is just prevented from doing sports. Or else if it's serious and not fixable then pregnancy is terminated.

So I would expect the actual mortality to be substantially less than 2x. And given that heart-related mortality in children is extremely rare, I suspect it would be quite tricky to detect. Especially when you need to account for confounding issues like maternal age during pregnancy, ICSI use, etc.

Given that there are around 5,000 CHD-related deaths in children per year, and around 1.5% of babies are IVF births, we're talking at most 150 deaths per year instead of 75, probably less due to the reasons mentioned above. And once you start trying to take into account imperfect data confounding variables, it's hard to say whether having definitive proof one way or the other is even within the realm of science at that point.

Embryo selection is an advantage for IVF children

Parents' primary responsibility is to ensure that the environment in which their kids grow up, the food they eat etc promote healthy development. For many practical purposes, the kids' protein-building machinery including the nucleic acids, can be treated the same way as the environment, the food etc - another critical input to a developing human life.

In this view, it is scarcely surprising that parents would want to give their kids viable genetic information just like they want to give their kids a good home, healthy food and challenging education.

This desire to ensure the good of the kids is a strong force pushing humanity forward and I see no reason to object.

Unequal access to shelter, food, education or genetic techniques is a different matter. But our failure to ensure universal access to the spoils of a new invention does not imply that there is something wrong with the invention. The real problem is more like the lack of compassion for other folks...

So let's not throw the baby out with the bathwater.

> 2. This will lead to a massive rise in availability of human eggs for scientific research, accelerating many fields. Lack of availability of eggs (as they get prioritized for other uses) restricts things like embryo research and other genetic analysis of human germline

Don't forget embryo selection: if you can create on demand several dozen or hundred eggs, the estimates of gains from embryo selection go from ~0.5 IQ points to 5-10 IQ points (and similarly for any other trait you might want to select for). 0.5 points is pretty trivial and no one will be beating down doors for that; 10 points, however, is a different proposition.

Perhaps more importantly, it's a step towards iterated embryo selection - fertilizing, selecting, then regressing to stem cells, and progressing to sperm/eggs - and doing so for multiple generations, getting +10 points each time, for largely unbounded gains.

Where are you getting the IQ boost from?

It's from my analysis of embryo selection (https://www.gwern.net/Embryo-selection). But you can do it without the complications by treating it as an order statistic (https://en.wikipedia.org/wiki/Order_statistic): what is the expected maximum of a sample of 5 Gaussians (rough current average egg harvest) vs 20 or 100 Gaussians, where the Gaussian is N(0, 0.5 * sqrt(polygenic score))? (Since you are selecting on the polygenic scores, not the unknown adult scores, and 0.5 because you are selecting from embryos which are 50% related ie. siblings.) X_5 vs X_100 is a big difference.

(To save you the trouble, it's +1.16SD vs +2.51SD; the difference is actually much bigger than it looks because you lose so many embryos in the IVF process, so it's really more like X_1 vs X_196 or +0.56 vs +2.48SD, but to be more precise, you need to go into the weeds of PGSes and per-stage losses in IVF etc. But the order statistics are a good starting point.)

What's the reason for thinking the gains are unbounded? AFAICT we could reasonably suppose something like 50 IQ points is within reach via embryo selection, but what would a something like a 300 IQ even mean, and even if it does mean something tangible, why should we assume that's biologically reachable in the same way that a 150 IQ would be?

Since historical estimates of figures like von Neumann or Sidis are more like +70-100 points, I would add at least 20 to that as the lower bound on the upper bound. Since such people existed, at least that much must be possible.

Of course, there's no way to definitively prove there's any potential to reach above that short of the existence proof of actually creating such people, but there's a lot of considerations which point to much more being possible: many complex traits have been pushed by selective breeding by many SDs, no one has ever been remotely close to genetically optimal and humans are minimally selected for intelligence, there's a large mutation load in terms of gene breakage, absolute measures of cognitive functioning like vocab size or digit span or reaction time generally show humans are nowhere near limits, brain scaling laws do not put humans at near any 0 marginal returns point, etc.

Even if there really is a bound at +100 and being able to increase IQ that much doesn't impress you for some reason, then you can simply spend your selection power on selecting for everything else... I shouldn't need to point out that many other traits are very important aside from intelligence.

When you wrote "largely unbounded gains" I thought not only in terms of genetic potential but also the impact on science / technology / society / culture this would likely have.

Pulling numbers out of a hat here: if we could have even, say, 0.015% of the global population, approximately 1 million people, with an IQ of ~200, the effects on the evolution of knowledge could be staggering.

If you look at actual people with 190+ IQ's their contributions are generally minor. We estimate that historic people that did great things had very high IQ's but that's our biases talking.

EX: Garry Kasparov is often said to have a sky high IQ but he tested at 135. He did however have an unusually good memory.

Do we even know whether IQ is all that comprehensive a test of the different aspects of intelligence? Memory obviously plays a large role in many ways.

But IQ tests are affected by memory, quite a bit. Memory tests are in fact some of the best ways to measure intelligence, like backwards digit span. Unsurprisingly, the genetics of memory and IQ overlap as do lots of other cognitive traits (https://en.wikipedia.org/wiki/Genetic_correlation#Intelligen...).

Lol, I'll take your word as a good authority, and read up. I imagine you've looked into it more than the average person... ;)

>if it does mean something tangible, why should we assume that's biologically reachable in the same way that a 150 IQ would be?

For that, consider the case of distinguished mathematicians who did not score high on IQ like tests.

If we had the tech to do that we would already have the ability to genetically modify embryos with heightened intelligence. Do we even know what genes are responsible for that?

Found your counter interesting so looked up this[1].

We already have the tech to do selection as above but it is cost prohibitive to produce the number of embryos required to do it at scale.

Where you misunderstood was that this is selection, not modification.

We do not know which genes to modify specifically.

We can however, using commonality and statistics, select embryos for increased likelihood of increased intelligence based on a number of different phenotypes.

That's where my understanding ends but the link below has more.

The interesting idea was that we can repeat the selection process using the already selected for embryos - effectively skipping potentially many generations. As in, your kids could more correctly be your great great great great great grandkids.

What I want to know is how far you could theoretically take it before the statistical analysis starts to break down.

As in, can we get to twice as intelligent? Does our statistics / scoring even know what that might look like?

Could we be looking at human induced evolution?

[1] https://www.gwern.net/Embryo-selection#polygenic-scores-for-...

> As in, can we get to twice as intelligent? Does our statistics / scoring even know what that might look like?

No to your second question; that being the case, your first question has no meaning.

We don't score intelligence with cardinal numbers, which would be required for "twice as intelligent" to make sense as a concept.

> We don't score intelligence with cardinal numbers, which would be required for "twice as intelligent" to make sense as a concept.

We actually do score intelligence with cardinal numbers if one wants to. As I mentioned in my other comment, a number of subtests have absolute scales with true zeros: digit span, vocab, and reaction time come to mind. Quite helpful for cross-species comparisons like humans and chimpanzees...

The fact that we score some intelligence correlates on scales with true zeros does not mean intelligence itself can be treated this way. Indeed, since the rigorous way to define intelligence is to do so perturbatively (e.g., as a certain principal components in data, or as the first-order effects of flipping a bunch of SNPs), we should generically expect it to break down as a robust concept outside the perturbative regime.

Or in other words, the fact that one person can be twice as fast as another person in the 100m dash does not make it meaningful to say that one person is twice as athletic as another. In particular, we don't expect the person who is twice as fast to also be twice as flexible or throw the shot-put twice as far, even if those can be made true statements for small (e.g. 5%) difference with appropriate multiplicative factors (e.g., a 5% increase in top-speed predicts a 10% = 2*5% increase in shot-put distance).

> Or in other words, the fact that one person can be twice as fast as another person in the 100m dash does not make it meaningful to say that one person is twice as athletic as another.

It does make it meaningful to say they are twice as fast, though. Which provides a basis for discussing improvements to the general factor. Since there are meaningful zeroes for speed or flexibility or throw distance, it must also be meaningful to discuss doubling the effect of fitness on them. Whether it works out in practice is the question, but it is meaningful and not nonsense.

> Since there are meaningful zeroes for speed or flexibility or throw distance, it must also be meaningful to discuss doubling the effect of fitness on them.

I feel like something's gotten switched around here. We can measure reaction time with cardinal numbers. Check.

This makes it meaningful to talk about doubling or halving reaction time. Check.

We could attribute part of reaction time performance to the general factor of intelligence. OK... but this will be variable.

It's not obvious to me that if we allot responsibility for someone's reaction time scores among several factors, perform an intervention, get improved reaction times, perform the same allocation, and calculate that the contribution from g has doubled, that we can then conclude that the subject's g has itself doubled.

We want to measure that g has doubled, and we have no numbers for that.

> Since there are meaningful zeroes for speed or flexibility or throw distance, it must also be meaningful to discuss doubling the effect of fitness on them.

If the effect of fitness on speed is small (as a fraction of absolute speed), then doubling the effect has little to do with doubling speed. If it's large (order unity), then we don't generically expect to be able to double the effect while staying in the regime where intelligence is well defined. These two notions of double are just completely different -- one is a derivative, one is a magnitude -- and it's a mistake to link them.

I don't think you read the article. The process is the growing of pre-existing egg cells from ovarian tissues into mature egg cells.

> This will enable older women to have kids and solve some reproductive issues.

Under 35, the success rate for IVF is ~40%. Between 35 and 42, it's about 10%. After 42 it's about 4%. Each time you try it costs around 20k, albeit sometimes the first one or two tries are subsidized by insurance or state grants. And there are also all sorts of health risks to both the mother and baby.

So even if you can safely create unlimited eggs at a nominal cost, I don't see this having any practical effect on family planning. (Other than as a treatment for certain infertility issues.)

Given that it takes around two years to have a baby, pragmatically you're still going to ideally want to start having kids no later than 35 - 2 * (desired kids), at least for the foreseeable future.

20k! Here in the UK, the NHS will pay for up to 3 attempts (only if you haven't been able to conceive naturally), but even if you pay privately the cost is around 4k USD.

More like $7,000. Your point still stands of course. US healthcare is typically twice as expensive as equally high income nations. Adjust the $7k UK figure up to US income levels, you get around $10k. So that 2x rate remains pretty accurate.

https://www.nhs.uk/conditions/ivf/

> Potentially this could lead to gay couples being able to have genetically descended children (obviously male couples here, but similar work on sperm is being done that could potentially enable lesbian couples to have kids too)

I would actually argue that the latter (lesbian couple->kids) will become feasible first - https://www.theguardian.com/science/2016/feb/25/lab-created-...

Which probably means we will reduce the combinations of genes we use, more and more. And hence, lessen the genetic diversity of our specie. What can go wrong ?

    Using strips of ovarian tissue removed in a biopsy, it 
    represents an advance on IVF (in vitro fertilisation), 
    where a mature egg is fused with a sperm in the lab and 
    the fertilised embryo is implanted.

Eggs aren't frozen, but it still sounds like a painful and expensive process.

> This will enable older women to have kids and solve some reproductive issues.

AFAIK, there's far more problems to solve than just this before older women in general can just have kids like they're 20 again.

Surrogate pregnancies?

Other problems remain, such as genetic degradation and questions about epigentic content.

>gay couples being able to have genetically descended children

What steps are missing? I'm extremely interested in this but I've had a hard time finding more information.

Producing the egg cells from pluripotent stem cells, then figuring out any immune response from growing them in the system described in this article.

> This will lead to a massive rise in availability of human eggs for scientific research

Depending on where you are, that's not really a problem. We did IVF, and we still have an embryo left over. When we asked about donating it to science, they told us not to bother because it would just be thrown away, since they already have too many in California (the embryos can't cross state lines apparently).

Don’t you still have to do egg harvesting? Or where are these coming from?

Do we really want to increase the human races ability to procreate? We already have enough children that have been abandoned or live in terrible conditions. The earth is overpopulated as it is.

This has many implications, not the least of which that the simplest way to reduce carbon emissions is fewer people.

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