Thanks for the detailed response. I appreciate your willingness to engage in dialogue.
To clarify: I didn’t mean to imply that you literally stated hypertension is caused by a single gene – rather, I was pointing to a broader pattern I noticed in your post, where complex traits seemed to be discussed in a somewhat reductionistway. That might not have been your intent, but that’s how it came across to me as a physician who deals with multifactorial conditions daily.
I also understand that emotional attachment wasn’t your focus – fair enough. Still, I think omitting it entirely risks presenting a view of childhood development that’s skewed towards instrumental or mechanistic thinking. For people unfamiliar with the developmental literature, that can unintentionally reinforce the idea that kids are optimization projects rather than human beings growing in relational contexts. If that wasn’t your goal, I’d just gently suggest flagging this limitation more clearly.
On the topic of predictability and engineering – sure, we can influence predispositions, but the point I was trying to make is epistemological: the level of uncertainty and interdependence in human development makes the engineering metaphor fragile. Medicine, to your point, does aim to “figure out” complex systems – but it’s also deeply aware of its limitations, unintended consequences, and historical hubris. That humility didn’t come through strongly in your piece, at least to me.
You clearly put a lot of thought into the genetic correlations and tradeoffs, and I don’t doubt your reasoning there. But I do wonder: do we really know enough about gene–environment interactions to be confident in the long-term effects of shifting polygenic profiles at scale? Especially given how much of our current “environment” is in flux, including things like diet, social structures, and digital exposure? These aren’t rhetorical questions – just areas where I think caution is warranted.
Again, I don’t mean this as a takedown – your post made me think, and that’s valuable. I just wanted to voice a perspective from someone who works directly with real human variability every day, where even “favorable” traits often come bundled with unexpected downsides.
On the topic of predictability and engineering – sure, we can influence predispositions, but the point I was trying to make is epistemological: the level of uncertainty and interdependence in human development makes the engineering metaphor fragile. Medicine, to your point, does aim to “figure out” complex systems – but it’s also deeply aware of its limitations, unintended consequences, and historical hubris. That humility didn’t come through strongly in your piece, at least to me.
Perhaps so. But the default assumption, seemingly made by just about everyone, is that there is nothing we can do about any of this stuff.
And that’s just wrong. The human genome is not a hopeless complex web of entangled interactions. Most of the variance in common traits is linear in nature, meaning we can come up with reasonably accurate predictions of traits by simply adding up the effects of all the genes involved. And thus by extension, if we could flip enough of these genes, we could actually change people’s genetic predisposition.
Furthermore, nature has given us the best dataset ever in genetics, which is billions of siblings that act as literal randomized control trials for the effect of genes on life outcomes.
If I felt that the world was suffering from excess genetic engineering hubris, then I might be more cautious in my language. But that is not in fact what is happening! What is happening is humanity is being far too cautious, mostly because they hold a lot of false assumptions about how complex the genome is.
We have this insane situation in reproductive genetics right now where tens of thousands of children are being born every year with much higher genetic predispositions towards disease than they should have because doctors don’t understand polygenic risk scores and would rather implant embryos that look nice under a microscope.
do we really know enough about gene–environment interactions to be confident in the long-term effects of shifting polygenic profiles at scale?
It depends what your standard is: if the bar we need to meet is “we can’t make any changes that might result in unpredictable effects”, then of course we can’t be confident.
But if the bar is “we know enough to say with high confidence improve the life of the child”, then we are already there for small changes, and can get there relatively soon for much larger ones.
Thanks for the detailed response. I appreciate your willingness to engage in dialogue.
To clarify: I didn’t mean to imply that you literally stated hypertension is caused by a single gene – rather, I was pointing to a broader pattern I noticed in your post, where complex traits seemed to be discussed in a somewhat reductionist way. That might not have been your intent, but that’s how it came across to me as a physician who deals with multifactorial conditions daily.
I also understand that emotional attachment wasn’t your focus – fair enough. Still, I think omitting it entirely risks presenting a view of childhood development that’s skewed towards instrumental or mechanistic thinking. For people unfamiliar with the developmental literature, that can unintentionally reinforce the idea that kids are optimization projects rather than human beings growing in relational contexts. If that wasn’t your goal, I’d just gently suggest flagging this limitation more clearly.
On the topic of predictability and engineering – sure, we can influence predispositions, but the point I was trying to make is epistemological: the level of uncertainty and interdependence in human development makes the engineering metaphor fragile. Medicine, to your point, does aim to “figure out” complex systems – but it’s also deeply aware of its limitations, unintended consequences, and historical hubris. That humility didn’t come through strongly in your piece, at least to me.
You clearly put a lot of thought into the genetic correlations and tradeoffs, and I don’t doubt your reasoning there. But I do wonder: do we really know enough about gene–environment interactions to be confident in the long-term effects of shifting polygenic profiles at scale? Especially given how much of our current “environment” is in flux, including things like diet, social structures, and digital exposure? These aren’t rhetorical questions – just areas where I think caution is warranted.
Again, I don’t mean this as a takedown – your post made me think, and that’s valuable. I just wanted to voice a perspective from someone who works directly with real human variability every day, where even “favorable” traits often come bundled with unexpected downsides.
Perhaps so. But the default assumption, seemingly made by just about everyone, is that there is nothing we can do about any of this stuff.
And that’s just wrong. The human genome is not a hopeless complex web of entangled interactions. Most of the variance in common traits is linear in nature, meaning we can come up with reasonably accurate predictions of traits by simply adding up the effects of all the genes involved. And thus by extension, if we could flip enough of these genes, we could actually change people’s genetic predisposition.
Furthermore, nature has given us the best dataset ever in genetics, which is billions of siblings that act as literal randomized control trials for the effect of genes on life outcomes.
If I felt that the world was suffering from excess genetic engineering hubris, then I might be more cautious in my language. But that is not in fact what is happening! What is happening is humanity is being far too cautious, mostly because they hold a lot of false assumptions about how complex the genome is.
We have this insane situation in reproductive genetics right now where tens of thousands of children are being born every year with much higher genetic predispositions towards disease than they should have because doctors don’t understand polygenic risk scores and would rather implant embryos that look nice under a microscope.
It depends what your standard is: if the bar we need to meet is “we can’t make any changes that might result in unpredictable effects”, then of course we can’t be confident.
But if the bar is “we know enough to say with high confidence improve the life of the child”, then we are already there for small changes, and can get there relatively soon for much larger ones.