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Polygenic screening of embryos is here, but is it ethical?

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https://www.theguardian.com/science/2021...it-ethical

EXCERPTS: The birth of the first IVF baby, Louise Brown, in 1978 provoked a media frenzy. In comparison, a little girl named Aurea born by IVF in May 2020 went almost unnoticed. Yet she represents a significant first in assisted reproduction too, for the embryo from which she grew was selected from others based on polygenic screening before implantation, to optimise her health prospects.

For both scientific and ethical reasons, this new type of genetic screening is highly controversial. [...] The diseases conventionally screened with PGD are mostly caused by a mutation in only a single gene. They can be nasty but are typically rare. In contrast, most common health problems, such as heart diseases or type 2 diabetes, are polygenic: caused by complex interactions among several, often many, genes. Even if particular gene variants are known to increase risk, as for example with the BRCA1/2 variants associated with breast cancer, such links are probabilistic: there’s no guarantee that people with that variant will get the disease or that those who lack it will not.

That’s simply how most genes work: in complex, interconnected and often poorly understood ways, so that the gene variants an individual carries don’t guarantee which traits they will develop. And environmental factors such as upbringing and diet, as well as unpredictable quirks of embryo development, also have a role. We’re products of (genetic) nature, nurture, chance and an interplay between all three.

Yet the availability today of genetic data for many thousands of individuals, thanks to the plummeting costs of genome sequencing and the popularity of genomic profiling companies such as 23AndMe and Orchid, has transformed our understanding of how genes relate to traits. The technique known as a genome-wide association study (GWAS) can sift through vast databanks to look for statistical associations between an individual’s gene variants and pretty much any trait we choose...

So someone’s genetic profile – the variants in their personal genome – can be used to make predictions [...] Aurea’s embryo was chosen because of low PRSs for heart disease, diabetes and cancer. PRSs can be used to predict other things too, such as a child’s IQ and educational attainment.

But such predictions are probabilistic, both because we can’t say exactly how our genes will “play out” in influencing that trait and because genes aren’t the only influence anyway. So there’s nothing inevitable or deterministic about a PRS. An individual with a high PRS for skin cancer might never develop it, while someone who scores low might do so. Someone with a genetic profile that predicts a modest IQ might turn out to be brilliant.

This is one reason why using PRSs in embryo screening – which is legal and largely unregulated in the US – is controversial. Unlike single-gene diseases, where the health outcome can be almost certain, it’s not clear how much faith we can put in predictions for polygenic traits. Yet we make choices based on probabilities all the time.

[...] “There’s a scientific basis to the concept [of PRSs] and it’s a type of genetic assessment that has a future in medicine,” says bioethicist Vardit Ravitsky of the University of Montreal. Yet most regulators and many experts feel that there is not yet any justification for using them to try to improve the health outcomes of IVF children. “It’s not seen as ready for primetime use,” says Ravitsky. “It’s still at a research stage. So when you start jumping straight into implementation, especially in a reproductive context, you’re in a minefield.”...

[...] And once such screening methods are permitted, where does it stop? Already, American couples can screen embryos for gender, complexion and eye colour. What’s to stop a company offering to screen for a non-disease trait such as height or intelligence? “There’s no reason to think polygenic embryo screening will end with conditions like heart disease and diabetes,” says Katie Hasson, associate director of the CGS. “Screening for schizophrenia and other mental illnesses is already on offer. These directly echo eugenic efforts to eliminate ‘feeble-mindedness’. We are talking about deciding who should be born based on ‘good’ and ‘bad’ genes.”

[...] t’s not clear that screening for such non-disease traits would work anyway. “I think the things that parents are most interested in, like intelligence, sports and musical ability, will have extremely small to nonexistent convincing PRS results,” says Greely. A study in 2019 suggested that using polygenic screening to select embryos for height and IQ would be likely to make only a tiny difference on average – and there’s a fair chance you wouldn’t end up picking the “best” embryo.

So what should be permitted? [...] To avoid any Gattaca-style genetic stratification of society, Hsu has expressed the hope that “progressive governments will make this procedure free for everyone”. But Hasson believes that this wouldn’t solve the problems of inequality that such techniques could exacerbate. Even if PRSs for smartness, say, have little real predictive value, she says that “belief in genomic predictions can itself be a driver of intense inequalities in society” by reinforcing ideas of genetic determinism. “Families that invest their money, time and hopes in this kind of screening and selection will have children they believe are genetically superior and those children will be treated as superior by their parents, care-givers and educators.”

Social pressure could make it hard to resist polygenic screening if it’s on offer in our hyper-competitive societies. “Once you do IVF, you feel pressure to use any add-on service or test that the clinic offers you,” says Ravitsky. “Look at what happens today when a woman declines prenatal screening or amniocentesis. Many women feel judged, not just by peers but by healthcare providers.” The idea that it’s all about autonomy of choice can be an illusion, she says.

Even if PRSs have little real value in forecasting the prospects of a child, evidently a market exists for them. In countries such as the US where assisted conception is weakly regulated, companies can make unrealistic and exploitative promises [...] Yet the genie is out of the bottle...

“We urgently need public and policy conversations about polygenic embryo screening,” says Hasson. Finding the right balance between autonomy and social responsibility is the fundamental dilemma of liberal democracies. “We let people spend their money, and make decisions powerfully affecting their kids, on far more clearly bogus information than PRS,” says Greely. “As a society, we’re very far from knowing how we want to use these potential technologies,” says Ravitsky, but, she adds, “we are already living in the grey zone”... (MORE - missing details)
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