It never really got any traction. And I think you're right about the similarity to eugenics somewhat defeating the purpose.

I think terms like "reproductive freedom" or "reproductive choice" actually get the idea across better anyways since you don't have to stop and explain the meaning of the word.

This is one of my favorite articles I've read on this website in months. Since I'm guessing most people won't read the whole thing, I'll just quote a few of the highlights here:

Measles is an unremarkable disease based solely on its clinical progression: fever, malaise, coughing, and a relatively low death rate of 0.2%~. What is astonishing about the disease is its capacity to infect cells of the adaptive immune system (memory B‑ and T-cells). This means that if you do end up surviving measles, you are left with an immune system not dissimilar to one of a just-born infant, entirely naive to polio, diphtheria, pertussis, and every single other infection you received protection against either via vaccines or natural infection. It can take up to 3 years for one's ‘immune memory’ to return, prior to which you are entirely immunocompromised.

I had literally no idea Measles did this. As if I needed another reason to get vaccinated.

On the highest end, Alzheimer's received $3538M in funding in 2023, and caused 451 DALYs per 100k people worldwide. So, 3538:451, or 7.8.

Then Crohn’s Disease, which has the ratio 92:20.97 (4.3).

Slightly lower is diabetes, 1187:801.5 (1.4).

Close to it is epilepsy, 245:177.84 (1.6).

Finally, near the bottom of the list is endometriosis, 29:56.61, or .5.

It's kind of shocking there is such a big difference between diseases when it comes to funding. Literally a 16x discrepancy between Alzheimer's funding and endometriosis (and a 52x difference between Alzheimer's and COPD!) I so wish that DOGE had been functional because it's exactly situations like this that pose the biggest opportunity for improved government operations.

I think the most interesting part of this disease is how it's kind of sort of not really a form of cancer. It's basically cancer that causes a lot of issues but very rarely grows in the aggressive way that other cancers do.

The fact that you literally find endometrial lesions with some of the mutations that are hallmarks of cancer implies that there's probably a lot of endometriosis cases that are cleared up by the immune system naturally which no one ever finds out about. These mutations show up because they provide a survival advantage to the endometrial cells.

Minor nitpick about heritability

Lastly I have a very minor nitpick. The Nature paper you linked ostensibly showing very high heritability doesn't actually mention heritability in the abstract. The paper made a genetic predictor for endometriosis which explained 5% of the variance (not particularly high, especially given the sample size they were working with). 

It does cite a paper about heritability, but that paper doesn't showing endometriosis as being unusually heritable; it shows 47% of the variance can be explained by additive genetic factors. That's pretty middle-of-the-pack as far as heritability goes. Conditions like Alzheimer's and Schizophrenia are significantly more heritable; roughly 70% and 80% respectively.

Actual heritability of Endometriosis is likely somewhat higher than that because most conditions have some non-additive genetic variance. This paper (somewhat questionably) attributes the entire remainder of the variance to "unique environmental factors".

The actual genetics of the disease itself are almost shockingly polygenic. The study had 61k cases, yet only identified 42 genome-wide significant hits. I can't look at the rest of the paper due to a paywall (SciHub has stopped archiving new articles :() but it seems there aren't any especially common alleles with large effect sizes.

This actually strongly the supports the "multiple causes of endometriosis" narrative you explore in your post: if there are that many genetic variants with small effects, there are probably many different ways the disease can manifest (or at least many influences on when and how it shows up).

Sounds like we should talk

I agree this is a worry. Apart from this stuff just not mattering because AI takes over first, dramatic acceleration of inequality is my biggest worry.

This tech almost certainly WILL accelerate inequality at the start. But in the long run I think there's no reason we can't make gene editing available for almost everyone.

Editing reagents are cheap. We're working with at most a few microliters of editing agents (more realistically a few nanoliters).

It costs a lot of money to collect the data and put it into biobanks, but once that is done you've got the data forever.

And at SCALE the cost of absolutely everything comes down.

Maybe we'll get there someday. I think for the next decade at least it's going to be hard to beat lead paint elimination or animal welfare initiatives that get a hundred million chickens out of battery cages.

Care to explain how you think it's being misused?

I find this argument fairly compelling. I also appreciate the fact that you've listed out some ways it could be wrong.

Your argument matches fairly closely with my own views as to why we exist, namely that we are computationally irreducible

It's hard to know what to do with such a conclusion. On the one hand it's somewhat comforting because it suggests even if we fuck up, there are other simulations or base realities out there that will continue. On the other hand, the thought that our universe will be terminated once sufficient data has been gathered is pretty sad.

DE-FACTO UPLOADING

Imagine for a moment you have a powerful AI that is aligned with your particular interests.

In areas where the AI is uncertain of your wants, it may query you as to your preferences in a given situation. But these queries will be "expensive" in the sense that you are a meat computer that runs slowly, and making copies of you is difficult.

So in order to carry out your interests at any kind of scale with speed, it will need to develop an increasingly robust model of your preferences.

Human values are context-dependent (see shard theory and other posts on this topic), so accurately modeling one's preferences across a broad range of environments will require capturing a large portion of one's memories and experiences, since those things affect how one responds to certain stimuli.

In the limit, this internal "model" in the AI will be an upload. So my current model is that we just get brain uploading by default if we create aligned AGI.

I'm not sure I buy that they will be more cautious in the context of an "arms race" with a foreign power. The Soviet Union took a lot of risks their bioweapons program during the cold war.

My impression is the CCP's number one objective is preserving their own power over China. If they think creating ASI will help them with that, I fully expect them to pursue it (and in fact to make it their number one objective)

So in theory I think we could probably validate IQ scores of up to 150-170 at most. I had a conversation with the guys from Riot IQ and they think that with larger sample sizes the tests can probably extrapolate out that far.

We do have at least one example of a guy with a height +7 standard deviations above the mean actually showing up as a really extreme outlier due to additive genetic effects.

The outlier here is Shawn Bradley, a former NBA player. Study here

Granted, Shawn Bradley was chosen for this study because he is a very tall person who does not suffer from pituitary gland dysfunction that affects many of the tallest players. But that's actually more analogous to what we're trying to do with gene editing; increasing additive genetic variance to get outlier predispositions.

I agree this is not enough evidence. I think there are some clever ways we can check how far additivity continues to hold outside of the normal distribution, such as checking the accuracy of predictors at different PGSes, and maybe some clever stuff in livestock.

This is on our to-do list. We just haven't had quite enough time to do it yet.

The second point is the distinction between causal for the association observed in the data, and causal when intervening on the genome, I suspect more than half of the gene is only causal for the association. I also imagine there are a lot of genes that are indirectly causal for IQ such as making you an attentive parent thus lowering the probability your kid does not sleep in the room with a lot of mold, which would not make the super baby smarter, but it would make the subsequent generation smarter.

There are some, but not THAT many. Estimates from EA4, the largest study on educational attainment to date, estimated the indirect effects for IQ at (I believe) about 18%. We accounted for that in the second version of the model.

It's possible that's wrong. There is a frustratingly wide range of estimates for the indirect effect sizes for IQ in the literature. @kman can talk more about this, but I believe some of the studies showing larger indirect effects get such large numbers because they fail to account for the low test-retest reliability of the UK biobank fluid intelligence test.

I think 0.18 is a reasonable estimate for the proportion of intelligence caused by indirect effects. But I'm open to evidence that our estimate is wrong.