I’m a software developer by training with an interest in genetics. I currently run a startup working on multiplex gene editing technology.
GeneSmith
Karma: 5,004
Well we have it in cows. Just not in mice.
I think many people in academia more or less share your viewpoint.
Obviously genetic engineering does add SOME additional risk of people coming to see human children like commodities, but in my view it’s massively outweighed by the potential benefits.
you end up with a child whose purpose is to fulfill the parameters of their human designers
I think whether or not people (and especially parents) view their children this way depends much more on cultural values and much less on technology.
There are already some parents who have very specific goals in mind for their children and work obsessively to realize them. This doesn’t always work that well, and I’m not sure it will work that well even with genetic engineering.
Sure we will EVENTUALLY be able to shape personality better with gene editing (though I would note we don’t really have the ability to do so currently), but human beings are very complicated. Gene editing is a fairly crude tool for shaping human behavior. You can twist the knobs for dozens of human traits, but I think anyone trying to predetermine their child’s future is going to be disappointed.
The tremendous effort involved in trying to fit the child to the design parameters betrays a lack of belief in the child’s inherent value as themselves, and they will be able to tell.
The thing about this argument is you could easily apply it to other interventions like medicines or education. “The tremendous effort involved in trying to fit the child to the design parameters through tutoring and a specialized education program betrays a lack of belief in the child’s inherent value as themselves, and they will be able to tell.”
Does working hard to give your child the best shot of a healthy, happy and productive life show a lack of true affection for them? I think it shows the exact opposite; you loved them so much that you were willing to go to extra lengths to give them the best life you could. I think this is no different than parents moving to America to give their child a chance at economic opportunity, or parents working extra shifts to send their children to a better school.
But no “super” people can exist in an ethical system where people are of equal intrinsic worth.
The term “super” is not a description of the relative moral worth of these future children. It is a description of their capabilities and prospects for a healthy life.
Good genes enable human productivity and happiness. They don’t determine moral worth. That exists independent of ability.
Confering a genetic immunity to HIV on a child might help them out, but it does not, for example, license them to win the trolly problem.
Agreed. I don’t get the sense we have any disagreement about the moral worth of people being tied to their genetics.
It’s written to explore the principle that there are no bad genes, only genes badly adapted to their environments, and our heroine is an aspiring apprentice baby designer with sickle cell. While it’s a challenging position to take, I’m not sure it’s a bad guiding principle for somebody made of genes.
I think we need to separate judgment of genes from judgment of the people who have them. You are not your genes. Sure they shape you and influence your experience of the world, but I think a lot of these kinds of books make the mistake of starting with the mistaken premise that our worth IS determined by our genes, and then ask how we can still be equal.
I think the premise is just wrong. It’s like saying that you are your trauma, or you are your leg injury. People are much deeper than their experiences or their predispositions, even if all those things have a strong influence on their behavior.
I would love to try this in mice.
Unfortunately our genetic predictors for mice are terrible. The way mouse research works is not at all like how one would want it to work if we planned to actually use them as a testbed for the efficacy of genetic engineering.
Mice are mostly clones. So we don’t have the kind of massive GWAS datasets on which genes are doing what and how large the effect sizes are.
Instead we have a few hundred studies mostly on the effects of gene knockouts to determine the function of particular proteins.
But we’re mostly not interested in knockouts for genetic engineering. 2/3rds of the disease related alleles in humans are purely single letter base pair changes.
We have very little idea which specific single letter base pair changes affect things like disease risk in mice.
MAYBE some of the human predictors translate. We haven’t actually explicitly tested this yet. And there’s at least SOME hope here; we know that (amazingly), educational attainment predictors actually predict trainability in dogs with non-zero efficacy. So perhaps there’s some chance some of our genetic predictors for human diseases would translate at least somewhat to mice.
We do need to do more thorough investigation of this but I’m not really that hopeful.
I think a far better test bed is in livestock, especially cows.
We have at least a few hundred thousand cow genomes sequenced and we have pretty well labelled phenotype data. It should be sufficient to get a pretty good idea of which alleles are causing changes in breed value, which is the main metric all the embryo selection programs are optimizing for.
Yes, I pretty much agree with this
I’m not saying his experiments show germline editing is safe in humans. In fact He Jiankui’s technique likely WASN’T safe. Based on some talks I heard from Dieter Egli at Colombia, He was likely deleting chromosomes in a lot of embryos, which is why (if I recall correctly) only 3 out of about ~30 embryos that were transferred resulted in live birth. Normally the live birth rate per transfer rate would be between 30 and 70%.
It’s also not entirely clear how effective the editing was because the technique He used likely created a fair degree of mosaicism since the editing continued after the first cell division. If the cells that ended up forming hematopoietic stem cells DIDN’T receive the edits then there would have been basically no benefit to the editing.
Anyways, I’m not really trying to defend He Jiankui. I don’t think his technique was very good nor do I think he chose a particularly compelling reason to edit (HIV transmission can be avoided with sperm washing or anti-retroviral drugs to about the same degree of efficacy as CCR5 knockout). I just think the reaction was even more insane.
It doesn’t make sense to ban germline editing just because one guy did it in a careless way. Yet in many places that’s exactly what happened.
I’d be interested in hearing where specifically you think we are doing that.
Yes, the two other approaches not really talked about in this thread that could also lead to superbabies are iterated meiotic selection and genome synthesis.
Both have advantages over editing (you don’t need to have such precise knowledge of causal alleles with iterated meiotic selection or with genome synthesis), but my impression is they’re both further off than an editing approach.
I’d like to write more about both in the future.
It’s just very hard for me to believe there aren’t huge gains possible from genetic engineering. It goes against everything we’ve seen from a millenia of animal breeding. It goes against the estimates we have for the fraction of variance that’s linear for all these highly polygenic traits. It goes against data we’ve seen from statisitcal outliers like Shawn Bradley, who shows up as a 4.6 standard deviation outlier in graphs of height:
Do I buy that things will get noisier around the tails, and that we might not be able to push very far outside the +5 SD mark or so? Sure. That seems unlikely, but plausible.
But the idea that you’re only going to be able to push traits by 2-3 standard deviations with gene editing before your predictor breaks down seems quite unlikely.
Maybe you’ve seen some evidence I haven’t in which case I would like to know why I should be more skeptical. But I haven’t seen such evidence so far.
There is one saving grace for us which is that the predictor we used is significantly less powerful than ones we know to exist.
I think when you account for both the squaring issue, the indirect effect things, and the more powerful predictors, they’re going to roughly cancel out.
Granted, the more powerful predictor itself isn’t published, so we can’t rigorously evaluate it either which isn’t ideal. I think the way to deal with this is to show a few lines: one for the “current publicly available GWAS”, one showing a rough estimate of the gain using the privately developed predictor (which with enough work we could probably replicate), and then one or two more for different amounts of data.
All of this together WILL still reduce the “best case scenario” from editing relative to what we originally published (because with the better predictor we’re closer to “perfect knowledge” than where we were with the previous predictor.
At some point we’re going to re-run the calculations and publish an actual proper writeup on our methodology (likely with our code).
Also I just want to say thank you for taking the time to dive deep into this with us. One of the main reasons I post on LessWrong is because there is such high quality feedback relative to other sites.
Ha, sadly it is a pseudonym. My parents were neither that lucky nor that prescient when it came to naming me.
A brief summary of the current state of the “making eggs from stem cells” field:
We’ve done it in mice
We have done parts of it in humans, but not all of it
The main demand for eggs is from women who want to have kids but can’t produce them naturally (usually because they’re too old but sometimes because they have a medical issue). Nobody is taking the warning to not “Build A Method For Simulating Ovary Tissue Outside The Body To Harvest Eggs And Grow Clone Workers On Demand In Jars” because no one is planning on doing that.
Even if you could make eggs from stem cells and you wanted to make “clone workers”, it wouldn’t work because every egg (even those from the same woman) has different DNA. They wouldn’t even be clones.
Thanks for catching that! I hadn’t heard. I will probably have to rewrite that section of the post.
What’s your impression about the general finding about many autoimmune variants increasing protection against ancient plauges?
No, the problem really is technical right now.
There may be additional societal and political problems afterwards. But none of those problems actually matter unless the technology works.
Obviously we are going to do it in animals first. We have in fact DONE gene editing in animals many times (especially mice, but also some minor stuff in cows and other livestock). But you’re correct that we need to test massive multiplex editing. My hope is we can have good data on this in cows in the next 1-3 years.
I don’t understand your question
Agreed, though unfortunately it’s going to take a while to make this tech available to everyone.
Also, if you want to prevent your children from getting hypertension, you can already do embryo selection right now! The reduction isn’t always as large as what you can get for gene editing, but it’s still noticeable. And it stacks generation after generation; your kids can use embryo selection to lower THEIR children’s disease risk even more.
Kman and I probably differ somewhat here. I think it’s >90% likely that if we continue along the current trajectory we’ll get AGI before the superbabies grow up.
This technology only starts to become really important if there’s some kind of big AI disaster or a war that takes down most of the world’s chip fabs. I think that’s more likely than people are giving it credit for and if it happens this will become the most important technology in the world.
Gene editing research is much less centralized than chip manufacturing. Basically all of the research can be done in normal labs of the type seen all over the world. And the supply chain for reagents and other inputs is much less centralized than the supply chain for chip fabrication.
You don’t have a hundred billion dollar datacenter than can be bombed by hypersonic projectiles. The research can happen almost anywhere. So this stuff is just naturally a lot more robust than AI in the event of a big conflict.
Yes you’re right. With current technology there’s no way you could get anywhere close to 500 embryos. I know a couple trying to get 100 and even that seems crazy to me.
5-20 is more realistic for most people (and 5 is actually quite good if you have fertility issues).
But we wanted to show 500 edits to compare scaling of gene editing and embryo selection and there wasn’t any easy way to do that without extending the graph for embryo selection.
Currently, we have smart people who are using their intelligence mainly to push capabilities. If we want to grow superbabies into humans that aren’t just using their intelligence to push capabilities, it would be worth looking at which kind of personality traits might select for actually working on alignment in a productive fashion.
I think we need to think more broadly than this. There’s some set of human traits, which is a combination of the following:
Able to distinguish prosocial from antisocial things
Willing and able to take abstract ideas seriously
Long term planning ability
Desire to do good for their fellow humans (and perhaps just life more broadly)
Like, I’m essentially trying to describe the components of “is reliably drawn towards doing things that improve the lives of others”. I don’t think there’s much research on it in the literature. I haven’t seen a single article discuss what I’m referring to.
It’s not exactly altruism, at least not the naive kind. You want people that punish antisocial behavior to make society less vulnerable to exploitation.
Whatever this thing is, this is one of the main things that, at scale, would make the world a much, much better place.
I’m glad you liked the article!
Brain size is correlated with intelligence at maybe 0.3-0.4. If you were to just brain size max I think it would probably not yield the outcomes you actually want. It’s better to optimize as directly as you can for the outcome you want.
First of all, no one has really done large scale genetic engineering of animals before, so we wouldn’t know.
Almost all mouse studies or genetic studies in other animals are very simple knockout experiments where they break a protein to try to assess its function.
We really haven’t seen a lot of multiplex editing experiments in animals yet.
But even if someone were to do that it would be hard to evaluate the effects on intelligence in animals.
The genetic variants that control IQ in humans don’t always have analogous sequences in animals. So you’d be working with a subset of possible edits at best.
The first proof of concept here will probably be something like “do tons of edits in cows to make them produce more milk and beef”. In fact, that’s one of the earliest commercial applications of this multiplex editing tech.
We’re hoping to show a demonstration of this in the next couple of years as one of the first steps towards demonstrating plausible safety and efficacy in humans.