On 5 December, a U.S. company called Orchid Health announced that it would begin to offer fertility clinics and their hopeful customers the unprecedented option to sequence the whole genomes of embryos conceived by in vitro fertilization (IVF). “Find the embryo at lowest risk for a disease that runs in your family,” touts the company’s website. The cost: $2500 per embryo.
Although Orchid and at least two other companies have already been conducting more limited genetic screening of IVF embryos, the new test offers something more: Orchid will look not just for single-gene mutations that cause disorders such as cystic fibrosis, but also more extensively for medleys of common and rare gene variants known to predispose people to neurodevelopmental disorders, severe obesity, and certain psychiatric conditions such as schizophrenia.
That new offering drew swift backlash from genomics researchers who claim the company inappropriately uses their data to generate some of its risk estimates. The Psychiatric Genomics Consortium (PGC), an international group of more than 800 researchers working to decode the genetic and molecular underpinnings of mental health conditions, says Orchid’s new test relies on data it produced over the past decade, and that the company has violated restrictions against the data’s use for embryo screening.
PGC objects to such uses because its goal is to improve the lives of people with mental illness, not stop them from being born, says University of North Carolina at Chapel Hill psychiatrist Patrick Sullivan, PGC’s founder and lead principal investigator. The group signaled its dismay on the social media platform X (formerly Twitter) last week, writing, “Any use for commercial testing or for testing of unborn individuals violates the terms by which PGC & our collaborators’ data are made available.” PGC’s response marks the first time an academic team has publicly taken on companies using its data to offer polygenic risk scores.
Orchid didn’t respond to Science’s request for a comment and PGC leaders say they don’t have any obvious recourse to stop the company. “We are just a confederation of academics in a common purpose. We are not a legal entity,” Sullivan notes in an email to Science. “We can publicize the issue (as we are doing!) in the vain hope that they might do the right thing or be shamed into it.” (After this story was published, an Orchid spokesperson told Science the company did not use PGC’s data, but declined to share whose data it used or whether it gathered such data itself.)
Andrew McQuillin, a molecular psychiatry researcher at University College London, has previously worked with PGC and he echoes the group’s concern. It’s difficult for researchers to control the use of their data post publication, especially when so many funders and journals require the publication of these data, he notes. “We can come up with guidance on how these things should be used. The difficulty is that official guidance like that doesn’t feature anywhere in the marketing from these companies,” he says.
For more than a decade, IVF clinics have been able to pluck a handful of cells out of labmade embryos and check whether a baby would inherit a disease-causing gene. Even this more limited screening has generated debate about whether it can truly reassure potential parents an embryo will become a healthy baby—and whether it could lead to a modern-day form of eugenics.
But with recent advances in sequencing, researchers can read more and more of an embryo’s genome from those few cells, which can help create so-called polygenic risk scores for a broad range of chronic diseases. Such scores calculate an individual’s odds of developing common adult-onset conditions that result from a complex interaction between multiple genes as well as environmental factors.
Orchid’s new screening report sequences more than 99% of an embryo’s DNA, and estimates the risk of conditions including the irregular heart rhythm known as atrial fibrillation, inflammatory bowel diseases, types 1 and 2 diabetes, breast cancer—and some of the psychiatric conditions that PGC studies. In an August preprint on bioRxiv, Orchid scientists concluded that their whole genome sequencing methods using a five-cell embryo biopsy were accurate and effective at reading the depth and breadth of the genome.
But even with the most accurate sequencing, polygenic risk scores don’t predict disease risk very well, McQuillin says. “They’re useful in the research context, but at the individual level, they’re not actually terribly useful to predict who’s going to develop schizophrenia or not.”
In an undated online white paper on how its screening calculates a polygenic risk score for schizophrenia, Orchid cites studies conducted by PGC, including one that identified specific genetic variants linked to schizophrenia. But James Walters, co-leader of the Schizophrenia Working Group at PGC and a psychiatrist at Cardiff University’s Centre for Neuropsychiatric Genetics and Genomics, says the data use policy on the PGC website specifically indicates that results from PGC-authored studies are not to be used to develop a test like Orchid’s.
Some groups studying controversial topics such as the genetics of educational attainment (treated as a proxy for intelligence) and of homosexuality have tried to ensure responsible use of their data by placing them in password-protected sites. Others like PGC, however, have made their genotyping results freely accessible to anyone and relied on data policies to discourage improper use.
Orchid’s type of embryo screening may be “ethically repugnant,” says geneticist Mark Daly of the Broad Institute, but he believes data like PGC’s must remain freely available to scientists in academia and industry. “The point of studying the genetics of disease is to provide insights into the mechanisms of disease that can lead to new therapies,” he tells Science.
Society, McQuillin says, must soon have a broader discussion about the implications of this type of embryo screening. “We need to take a look at whether this is really something we should be doing. It’s the type of thing that, if it becomes widespread, in 40 years’ time, we will ask, ‘What on earth have we done?’”
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