Would a test of my father's embryo have predicted the man he would become?
Polygenic risk scoring makes predictions about the person the embryo will become. My dad is 92. Would his score have told us what we needed to know?
Last October, I wrote about polygenic risk scoring of embryos. It's a way of predicting what traits and conditions the person who develops from the embryo will go on to have.
We're told, for instance, that this sort of testing can make good guesses about whether a person will go on to have coronary artery disease, high blood pressure, certain types of cancer and so on. We're told that it makes sense to pick embryos that have fewer of these strikes against them. Some testing also claims to predict non-medical traits, like eye colour and height and even intelligence.
There are parents doing IVF right now who are using these tests to choose which embryos to transfer.
Polygenic risk scoring leans on findings from a large number of "genome wide association studies." These studies evaluate hundreds or thousands of tiny genetic variations in a people's DNA, and find the complex combinations that seem to predispose those people to traits or conditions we know they have. The tests then use those findings to make predictions about embryos.
While writing that piece, I kept thinking about my 92-year-old father. We know exactly how the embryo turned out. But what would polygenic risk scoring of his embryo have told us about the man he would become?
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If my father's DNA had been tested back when he was just an embryo, he probably wouldn't have shown all that well. Would his parents have picked him?
Now that he's in his nineties, we know how the embryo turned out. There was the gallbladder that had to be removed in his thirties. Unexplained asthma presented around age 44. He needed quadruple bypass surgery at age 63, and four stents a decade later. He has ongoing high blood pressure, high cholesterol, high blood lipids. A bum knee that needed replacing. Later, cancer.
Who'd pick an embryo like that?
In his defence, he's 92 and counting, still alive and well. Great fun to talk to and joke around with, or to commiserate with over the state of the world. So, despite what would probably have been an unimpressive polygenic score before birth, in a high-income country with universal healthcare, it didn't matter much. Modern medicine is remarkably effective at managing many of the things we are scoring embryos for these days. There are drugs, there are surgeries. We're actually pretty ace at treating a lot of these things and making them go away.
Maybe polygenic scoring would have accurately predicted that he wouldn't develop certain things: diabetes, obesity, other types of cancer. But is the absence of some bad things enough to offset the presence of others when you're trying to select an embryo?
Polygenic scoring predicts non-medical stuff too. So, on the plus side, my dad was taller than average. He was intelligent as well, and although they say they don't measure that, we all know that they at least believe they can; and in any case, I suspect my dad has a kind of intelligence that they're probably not bad at predicting. He was a mechanical engineer after all. Has a great memory. Excellent executive function.
Would intelligence make up for the coronary artery disease?
Some researchers boast that they are able to predict more elusive traits like "creativity" and "satisfaction with life." To be honest, I'm sceptical of such claims. But, okay, my father does have these, so maybe they would have boosted his score a bit.
But it's here, in the tangle of the very-difficult-to-measure, where I get most worried about the limits of polygenic scoring. Even though I skew very heavily in favour of genes as determinants of who we become, I know there are some traits we can barely name, let alone characterize and find genetic underpinnings for.
And if the test doesn't search, it won't find. So it seems to me that some of the finest human traits will go unselected while we fuss over height and blood pressure and blue eyes.
I'm thinking about my dad again. About how the ineffables are what really make the man.
I mean, like his laugh. The way, when he finds something really, really funny, his eyes crinkle shut and he starts to cry. It's absolutely infectious! Given a choice, wouldn't you choose an embryo that had a really good laugh?
Or his easy connection with people. The way he can sit down on a bench, anywhere in the world, and make a buddy. He'll hear the whole life story then retell it like a movie. What's that trait even called? Wouldn't you choose it for your kid, though, if you knew what it was?
Or his strength. Not physical strength anymore, but, you know, forbearance, stoicism, bravery. How to score that?
We can unblock hearts, lower blood pressure, cut out cancers. But the really important traits so far remain unmeasurable. Integrity. Kindness. Grace. I'm not saying we shouldn't try to reduce human suffering. I'm just saying we might be going about it the wrong way.
On ranking embryos best to worst. HeyReprotech. 12 Oct, 2021.
Polygenic Scores, Broad Institute