I’m a software developer by training with an interest in genetics. I currently run a startup working on multiplex gene editing technology.
GeneSmith
Do you have any estimate of how much more expensive testing in cynomolgus macaques or rhesus monkeys would be?
The issue is that it takes a long time for PGC-like cells to develop to eggs, if you’re strictly following the natural developmental trajectory.
Thanks for the clarification. I’ll amend the original post.
It’s a fair concern. But the problem of predicting personality can be solved! We just need more data.
I also worry somewhat about brilliant psychopaths. But making your child a psychopath is not necessarily going to give them an advantage.
Also can you imagine how unpleasant raising a psychopath would be? I don’t think many parents would willingly sign up for that.
Very little at the moment. Unlike intelligence and health, a lot of the variance in personality traits seems to be the result of combinations of genes rather than purely additive effects.
This is one of the few areas where AI could potentially make a big difference. You need more complex models to figure out the relationship between genes and personality.
But the actual limiting factor right now is not model complexity, but rather data. Even if you have more complex models, I don’t think you’re going to be able to actually train them until you have a lot more data. Probably a minimum of a few million samples.
We’d like to look into this problem at some point and make scaling law graphs like the ones we made for intelligence and disease risk but haven’t had the time yet.
It’s a good question. The remarkable thing about human genetics is that most of the variants ARE additive.
This sounds overly simplistic, like it couldn’t possible work, but it’s one of the most widely replicated results in the field.
There ARE some exceptions. Personality traits seem to be mostly the result of gene-gene interactions, which is one reason why SNP heritability (additive variance explained by common variants) is so low.
But for nearly all diseases and for many other traits like height and intelligence, ~80% of variance is additive.
This might seem like a weird coincidence. After all, we know there is a lot of non-linearity in actual gene regulatory networks. So how could it be that all the common variants simply add together?
There’s a pretty clear reason from an evolutionary point of view: evolution is able to operate on genes with additive effects much more easily than on those with non-additive effects.
The set of genetic variants inherited is scrambled every generation during the sperm and egg formation process. Those that need other common variants present to work their effects just have a much harder time spreading among the population because their benefits are inconsistent across generations.
So over time the genome ends up being enriched for additivity.
There IS lots of non-additivity happening in genes which are universal among the human population. If you were to modify two highly conserved regions, the effects of both edits could end up being much greater or much less than the sum of the effects of the two individual variants. But that’s also not that surprising; evolution has had a lot of time to build dependencies on these regions, so we should expect modifying them to have effects that are hard to predict.
You also had a second question embedded within your first, which is about second order effects from editing, like increased IQ resulting in more mental instability or something.
You can just look at people who naturally have high IQ to see whether this is a concern. What we see is that, with the exception of aspbergers, higher IQ actually tends to be associated with LOWER rates of mental illness.
Also you can see from my chart looking at genetic correlations between diseases that, with a few exceptions, there just isn’t that much correlation between diseases. The set of variants that affects two different diseases are mostly disjoint sets.
Yes, that’s more or less the plan. I think it’s pretty much inevitable that the United States will fully legalize germline gene editing at some point. It’s going to be pretty embarassing if rich American parents are flying abroad to have healthier children.
You can already see the tide starting to turn on this. Last Month Nature actually published an article about germline gene editing. That would NEVER have happened even just a few years ago.
When you go to CRISPR conferences on gene editing, many of the scientists will tell you in private that germline gene editing makes sense. But if you ask them to go on the record as supporting it publicly, they will of course refuse.
At some point there’s going to be a preference cascade. People are going to start wondering why the US government is blocking technology to its future citizens healthier, happier, and smarter.
This was a fun podcast. Thanks for having me on!
How to Make Superbabies
Probably because he thinks there’s a lower chance of it killing everyone if he makes it. And that if it doesn’t kill everyone then he’ll do a better job managing it than the other lab heads.
This is the belief of basically everyone running a major AGI lab. Obviously all but one of them must be mistaken, but it’s natural that they would all share the same delusion.
It’s nice to hear that there are at least a few sane people leading these scaling labs. It’s not clear to me that their intentions are going to translate into much because there’s only so much you can do to wisely guide development of this technology within an arms race.
But we could have gotten a lot less lucky with some of the people in charge of this technology.
I guess I somewhat agree with this, but I’ve also seen many examples of regulations that were passed in response to a particular incident decades ago, whose other non-incident related harms were completely ignored.
Compliance costs are real, and my experience dealing with the federal bureaucracy is that they’re often completely ignored.
Take my comments with a grain of salt because I haven’t thought too deeply about this, but if I think to myself what I would do if I was tasked with cutting government waste and modernizing IT systems, it would probably look something like what Musk is doing.
You have a sprawling complex of legacy systems, a federal bureaucracy that (let’s face it) is institutionally obsessed with process, often at the expense of getting thigns done. You’re tasked with cutting out fraud and bloat and increasing efficiency but everything is all over the place. So the first place you go is directly to the treasury, because at least government payments are centralized.
Could the power they’ve been given be abused? Yes of course. And I think it’s worth keeping an idea of signs that the team Musk has hired is abusing its authority.
If someone knows something I’m missing, such as clear signs that they’re using their power for self-dealing or to target political rivals, please let me know. But until I see such signs my attitude is mostly just “wait and see”.
EDIT: After talking about this more with a friend, I’m more concerned about DOGE. I think many of the things they’re doing are pretty blatantly unconstitional (changing allocation of funds in ways that a pretty obvious violations of article 1).
I personally find the defunding of USAID (especially PEPFAR) to be pretty horrible. That’s one of the best programs the government invests money in.
I think a lot of their actions will get thrown out by the courts. But they’ll do some damage in the meantime.
In hindsight, the answer here was “buy NVIDIA call options”
We’re pretty firmly committed to at least 3. I think whether we have more than that depends on how well we’re doing financially and whether the world is still around at that point.
Ask all your friends. How many are excited and aiming for 3+ children? Really excited and joyously motivated—not because it’s their duty for humanity and they’re on the EA burnout path. The life worth living is one with one child per couple among happy couples. Or 1.35 on average when you count the outliers.
I’m almost certainly somewhat of an outlier, but I am very excited about having 3+ children. My ideal number is 5 (or maybe more if I become reasonably wealthy). My girlfriend is also on board.
I just can’t picture anything more joyous in a normal life (i.e. excluding upload enabled perma-jhana) than finding someone I deeply love and combining ourselves to make new people. It’s a miracle that’s even possible! If this wasn’t a normal part of everyday life people would laugh at you for proposing such an absurd thing could ever be real.
EDIT: One more thing worth mentioning: If we ignore AGI for a second (not much point in talking about this otherwise), I think the long term solution to this problem is to create pro-natalist microcultures. Groups of friends living around each other raising their children in a shared environment. My dream is to live close to friends who also have a bunch of kids and raise them alongside people I love.
I know from reading reports of parents who have done or tried this that it’s not trivial. One of the most difficult parts seems to be getting everyone to agree to a set of parenting standards and having the flexibility and acceptance to not require perfect adherence to every rule from every parent all the time. But we are still going to try to make this happen, probably somewhere close by the bay area.
I think the response to 9/11 was an outlier mostly caused by the “photogenic” nature of the disaster. COVID killed over a million Americans yet we basically forgot about it once it was gone. We haven’t seen much serious investment in measures to prevent a new pandemic.
Seems like the only thing that could stop the train at this point is a few tens or hundreds of millions of deaths from out of control AI. Doesn’t seem like anyone in government wants to cooperate to reduce the risk of everyone dying. Both the US and China have individually decided to roll the dice on creating machines they don’t understand and may not be able to control.
I really should have done a better job explaining this in the original comment; it’s not clear we could actually make someone with an IQ of 1700, even if we were to stack additive genetic variants one generation after the next. For one thing you probably need to change other traits alongside the IQ variants to make a viable organism (larger birth canals? Stronger necks? Greater mental stability?). And for another it may be that if you just keep pushing in the same “direction” within some higher dimensional vector space, you’ll eventually end up overshooting some optimum. You may need to re-measure intelligence every generation and then do editing based on whatever genetic variants are meaningfully associated with higher cognitive performance in those enhanced people to continue to get large generation-to-generation gains.
I think these kinds of concerns are basically irrelevant unless there is a global AI disaster that hundreds of millions of people and gets the tech banned for a century or more. At best you’re probably going to get one generation of enhanced humans before we make the machine god.
For a given level of IQ controlling ever higher ones, you would at a minimum require the creature to decide morals, ie. is Moral Realism true, or what is?
I think it’s neither realistic nor necessary to solve these kinds of abstract philosophical questions to make this tech work. I think we can get extremely far by doing nothing more than picking low hanging fruit (increasing intelligence, decreasing disease, increasing conscientiousness and mental energy, etc)
I plan to leave those harder questions to the next generation. It’s enough to just go after the really easy wins.
additionally believe that they would not be able to persuade lower IQ creatures of such values, therefore be forced into deception etc.
Manipulation of others by enhanced humans is somewhat of a concern, but I don’t think it’s for this reason. I think the biggest concern is just that smarter people will be better at achieving their goals, and manipulating other people into carrying out one’s will is a common and time-honored tactic to make that happen.
In theory we could at least reduce this tendency a little bit by maybe tamping down the upper end of sociopathic tendencies with editing, but the issue is personality traits have a unique genetic structure with lots of non-linear interactions. That means you need larger sample sizes to figure out what genes need editing.
I can’t really speak to your specific experience too well other than to simply say I’m sorry you had to go through that. We actually see that in general, mental health prevalence actually declines with increasing IQ. The one exception to this is aspbergers.
I do think it’s going to be very important to address mental health issues as well. Many mental health conditions are reasonably editable; we could reduce the prevalence of some by 50%+ with editing.
Agreed. I’ve actually had a post in draft for a couple of years that discusses some of the paralleles between alignment of AI agents and alignment of genetically engineered humans.
I think we have a huge advantage with humans simply because there isn’t the same potential for runaway self-improvement. But in the long term (multiple generations), it would be a concern.