It’s very reasonable to worry about these things, but let me give you a couple of reasons why I am not very concerned about negative plieotropy:
We can observe in actual real humans right now that there is a negative correlation between IQ and disease risk. As you have pointed out, there are some exceptions to this such as autism risk. But the general picture is pretty optimistic.
Imagine for a moment that we have two sets of alleles: one set increases IQ. The other set increases disease risk. The sets are not disjoint; that is to say there are some alleles which both increase IQ AND disease risk. If we simply select for IQ, we will select both from the set of genes that ONLY increase IQ with no effect on disease, AND for the set of genes that both increase IQ and disease risk. If you add lower disease risk to your selection index, you will disproportionately select for alleles that are in the subset of variants that increase IQ without increasing disease risk. You’ll also select for some alleles that have no effect on IQ but decrease disease risk. Now you might be worried that perhaps there’s some disease that isn’t in our selection index but nonetheless has variants which increase both risk and IQ. Fortunately, there’s a way to deal with this too: add traits that are affected by pretty much all diseases to your selection criteria: for example:
Of cou
Likelihood of developing chronic pain
Self-rated quality of life
Life expectancy
The two companies that currently offer polygenic embryo screening are already selecting against or for some of these to a limited degree by using disease risk as a proxy. But they could and should select on them directly to deal with the problem you described.
In general, selective breeding of animals for various traits have often managed to produce animals that excel in that trait but are noticeably less healthy overall.
So I agree that if you select very very hard on a small set of traits, you are likely to get unforeseen downsides somewhere down the road. But two things worth considering here:
Some of the health problems in domesticated animals related to inbreeding rather than selection on a variety of traits.
Health was basically not used as a selective trait for livestock except insofar as it affected the traits that people actually cared about (namely meat, egg and milk production)
Domesticated animals have been pushed like a dozen or more standard deviations from their pre-selection means for many traits. We don’t have the selection power to do that with embryo selection except on a time scale of hundreds of years. It’s another story with like CRISPR editing or iterated embryo selection, so I do think we’ll have to be much more cognisant of that issue down the road.
We certainly can try to weigh the odds and try to avoid the cases where things have Obviously Gone Wrong, but I reserve the right to worry about removing genes from the human gene pool whose function we don’t understand.
We are not going to be removing any of these genes from the gene pool for a long time. It’s going to take 20-50 years for this technology to become widely adopted around the world. And even then, you’re unlikely to get the elimination of any genes without editing or iterated selection of some type.
I actually do agree with you here. At least in the short run, human knowledge probably already is better than past natural selection at picking genes that result in humans that end up healthy, intelligent, and fertile in the modern world that includes C-sections, baby formula, abundant calories, and antibiotics.
My wife’s family in particular tends to be very unhealthy and die young. She’s 31 now and if she manages to recover from her life-threatening medical conditions to the point that she can safely carry a pregnancy to term, it would help very much if we could do something to reduce our future child’s risk of obesity, type 2 diabetes, kidney disease, and heart disease so they won’t die before the age of 50.
I’m sorry to hear about your wife’s condition. I’ve had family members that have died young from diseases that most people get in old age as well. It’s a very painful experience.
If your outlook improves and you decide to do polygenic embryo screening, reach out to me and I can help give you a more personalized assessment of your prospects. The size of the absolute risk reduction you can get from embryo selection will actually be higher if your or your wife’s risk is higher. So the benefit will likely be higher for the two of you.
Also, the predictors for type 2, obesity, and heart disease are already very good, so if those are your concerns you’re in luck.
It’s very reasonable to worry about these things, but let me give you a couple of reasons why I am not very concerned about negative plieotropy:
We can observe in actual real humans right now that there is a negative correlation between IQ and disease risk. As you have pointed out, there are some exceptions to this such as autism risk. But the general picture is pretty optimistic.
Imagine for a moment that we have two sets of alleles: one set increases IQ. The other set increases disease risk. The sets are not disjoint; that is to say there are some alleles which both increase IQ AND disease risk. If we simply select for IQ, we will select both from the set of genes that ONLY increase IQ with no effect on disease, AND for the set of genes that both increase IQ and disease risk.
If you add lower disease risk to your selection index, you will disproportionately select for alleles that are in the subset of variants that increase IQ without increasing disease risk. You’ll also select for some alleles that have no effect on IQ but decrease disease risk.
Now you might be worried that perhaps there’s some disease that isn’t in our selection index but nonetheless has variants which increase both risk and IQ.
Fortunately, there’s a way to deal with this too: add traits that are affected by pretty much all diseases to your selection criteria: for example:
Of cou
Likelihood of developing chronic pain
Self-rated quality of life
Life expectancy
The two companies that currently offer polygenic embryo screening are already selecting against or for some of these to a limited degree by using disease risk as a proxy. But they could and should select on them directly to deal with the problem you described.
So I agree that if you select very very hard on a small set of traits, you are likely to get unforeseen downsides somewhere down the road. But two things worth considering here:
Some of the health problems in domesticated animals related to inbreeding rather than selection on a variety of traits.
Health was basically not used as a selective trait for livestock except insofar as it affected the traits that people actually cared about (namely meat, egg and milk production)
Domesticated animals have been pushed like a dozen or more standard deviations from their pre-selection means for many traits. We don’t have the selection power to do that with embryo selection except on a time scale of hundreds of years. It’s another story with like CRISPR editing or iterated embryo selection, so I do think we’ll have to be much more cognisant of that issue down the road.
We are not going to be removing any of these genes from the gene pool for a long time. It’s going to take 20-50 years for this technology to become widely adopted around the world. And even then, you’re unlikely to get the elimination of any genes without editing or iterated selection of some type.
I actually do agree with you here. At least in the short run, human knowledge probably already is better than past natural selection at picking genes that result in humans that end up healthy, intelligent, and fertile in the modern world that includes C-sections, baby formula, abundant calories, and antibiotics.
My wife’s family in particular tends to be very unhealthy and die young. She’s 31 now and if she manages to recover from her life-threatening medical conditions to the point that she can safely carry a pregnancy to term, it would help very much if we could do something to reduce our future child’s risk of obesity, type 2 diabetes, kidney disease, and heart disease so they won’t die before the age of 50.
I’m sorry to hear about your wife’s condition. I’ve had family members that have died young from diseases that most people get in old age as well. It’s a very painful experience.
If your outlook improves and you decide to do polygenic embryo screening, reach out to me and I can help give you a more personalized assessment of your prospects. The size of the absolute risk reduction you can get from embryo selection will actually be higher if your or your wife’s risk is higher. So the benefit will likely be higher for the two of you.
Also, the predictors for type 2, obesity, and heart disease are already very good, so if those are your concerns you’re in luck.