Simone Collins knew she was pregnant the moment she answered the phone. She was on her sixth round of in vitro fertilisation (IVF) treatments and had grown used to staffers at a Main Line Fertility clinic in the United States starting this kind of call with the words “Oh, hi, Simone,” in a subdued tone, voices brimming with sympathy. This time, though, on Valentine’s Day, the woman on the other end belted out a cheery “Oh, hi, Simone!” Embryo 3, the fertilised egg that Collins and her husband, Malcolm, had picked, could soon be their daughter – a little girl with, according to their tests, an unusually good chance of avoiding heart disease, cancer, diabetes and schizophrenia. But this is not a story about designer babies . No genes were edited in the creation of Collins’ embryo. The promise, from dozens of fertility clinics around the world, is just that the new DNA tests they are using can assess, in unprecedented detail, whether one embryo is more likely than the next to develop a range of illnesses long thought to be beyond DNA-based predictions. It’s a new twist on the industry-standard testing known as preimplantation genetic testing, which for decades has checked embryos for rare diseases, such as cystic fibrosis, that are caused by a single gene. One challenge with leading killers like cancer and heart disease is that they are usually polygenic: linked to many genes with complex interactions. Patients such as Collins can now take tests that assess thousands of DNA data points to decode these complexities and compute the disease risks. Couples may be offered DNA tests before having children in Hong Kong to detect hereditary diseases Genomic Prediction, the five-year-old New Jersey company that handled the tests for her fertility clinic, generates polygenic risk scores, predicting in percentage terms an embryo’s chances of contracting each disease in the panel, and providing a composite score for overall health. Parents with multiple embryos can weigh the scores when deciding which one to implant. They just might need to add a few grains of salt to the scale. In general, the percentage differences from embryo to embryo are slight and could well be outweighed by the effects of environmental factors. But Genomic Prediction adds up all the genetic data into overall health scores that start at a baseline for average risk of zero, with risk declining as the score rises. The embryo Collins and her husband selected had a score of 1.9, compared with a – 0.96 for their lowest-scoring embryo. Collins says that doesn’t feel minor to her. “It’s using the cutting edge of science to give your future children every advantage you can,” she says. “It’s giving kids a better roll of the dice.” This new form of genetic embryo testing appears to move humanity one step closer to control of its evolution. The US$14 billion IVF industry brings more than 500,000 babies into the world each year , and with infertility rates rising, the market is expected to more than double this decade. Companies including Genomic Prediction bet many going into that process have seen enough loved ones suffer from a polygenic disease to want risk scoring. “Everyone has someone in their family,” says CEO Laurent Tellier, whose mother has faced down multiple cancers. “Everyone.” Ten years ago, it wasn’t clear this kind of risk analysis would ever be possible, let alone practical. Over the past decade, advances in genetic testing have improved the technology’s efficiency at a pace faster than that of computer chips. Some lower-level DNA sequencing costs as little as US$40 now, and your whole genome could soon be mapped for US$100, a fraction of today’s cost. Choosing your healthiest-seeming embryo, after all, can only tell you so much about even the genetic influences on a child’s life Massive global DNA repositories allow researchers to draw connections between certain genes and all manner of life outcomes. Some studies correlate genes with height; others, with how far a person is likely to go in school. Genomic Prediction doesn’t offer scores on attributes unrelated to health, nor does rival Orchid, which is backed by Anne Wojcicki, the CEO of genetic testing giant 23andMe. But there are ways for motivated parents to get those kinds of predictions, and Collins and her husband did just that. Although choosing your embryo based on its odds of earning a graduate degree is still a long way off from eugenics, or even from the gene-editing tool Crispr , it is decidedly more fraught than efforts to minimise cancer risks. View this post on Instagram A post shared by Genomic Prediction (@genomicprediction) There’s some real daylight between the solid science behind polygenic scoring for disease risks and parental desires to pick the “perfect kid”. So as the science makes its way into leading peer-reviewed journals, it is yielding much more spirited debates than are usually seen in publications with names such as Fertility and Sterility . In general, the true believers say polygenic risk scoring should be available and clearly offered to everyone. Critics say it is a slippery slope towards designer babies. Sceptics say both camps are overselling how much we really know about what the testing can show and stress that genetic predispositions don’t lead to linear outcomes. Choosing your healthiest-seeming embryo, after all, can only tell you so much about even the genetic influences on a child’s life. Hong Kong genome study will help free babies from hereditary diseases This spring, the prestigious journal Nature warned that the “alarming rise” of polygenic embryo testing has run “well ahead of a full understanding of the potential benefits – or dangers”. Last autumn, Shai Carmi, a statistical geneticist at the Hebrew University of Jerusalem, published a study in the biomedical journal eLife that found that selecting an embryo with the lowest polygenic score for schizophrenia could reduce a future child’s risk by almost 50 per cent – with several important caveats. “There is accumulating evidence, based on modelling and simulation and some real data from families, that there is potential for risk reduction,” says Carmi. “But there are very serious limitations and practical problems.” View this post on Instagram A post shared by Genomic Prediction (@genomicprediction) Scores may not be as accurate as believed for all kinds of reasons – complex diseases are complex – and risk reductions may be lower in practice than modelling suggests, especially if parents have few embryos to choose from. And this finding on disease risks did nothing, he says, to challenge his research from a 2019 study published in the journal Cell , where he concluded that polygenic testing would likely have little effect on height (maybe an inch) or IQ (a couple of points). Still, he says, the disease-risk correlations are solid. More conservative critics argue even that data shouldn’t be attached to any grand promises until more definitive studies can be conducted over decades. Some people are just born with the cards stacked against them in a lot of ways, and other people are just born with a lot of luck. This is all we can do – help stack those odds Laurent Tellier, Genomic Prediction CEO Genomic Prediction says its testing simply builds on well-established methods. While it is tracking patient outcomes for a formal study, the underlying technology is widely accepted and the mass genetic data uncontested. “It’s just DNA,” says Nathan Treff, the company’s chief scientific officer. “We don’t have to wait for embryos to turn into adults, because we have the same information on adults that we get from an embryo.” If the scientific community can’t reach a consensus on these issues, is it possible for parents-to-be, who just want the best for their children, to separate the truth about the limitations of polygenic risk scores from the rosy promises? Well, let’s hope so, because the most important thing about the scores, and one that’s inarguable, is that polygenic scoring is already here. The initial process of polygenic embryo testing looks pretty comparable to the single-gene tests that have been around much longer. First, cells are drawn from an embryo a few days old, and the DNA is processed. Then proprietary software analyses the material, using data on hundreds of thousands of people, from DNA projects such as the UK Biobank, to translate genetic variations into odds for diseases. Since its founding in 2017, Genomic Prediction has used mathematical methods rooted in physics to draw information from even tiny quantities of embryo DNA. “These fancy methods are shown to actually work by looking at tens of thousands of real-world brother or sister pairs,” Tellier says, “and proving able to accurately predict which one has schizophrenia , or cancer, despite both being in the same family environment.” Bioethicists look at how to care for China’s gene-edited babies So far, one of the company’s more striking findings is that desirable health-related genes often appear to cluster in one embryo while risks of illness cluster in another. “It’s very cruel,” says Tellier, who was previously head of bioinformatics for a lab at BGI, China’s leading genomics company with headquarters in Shenzhen. “Some people are just born with the cards stacked against them in a lot of ways, and other people are just born with a lot of luck. This is all we can do – help stack those odds.” On a recent Monday at its pristine headquarters in North Brunswick, New Jersey, lab supervisor Heather Garnsey performs the final steps in the scientific equivalent of a four-day recipe to extract usable genetic information from embryo cells. Her processes amplify the DNA to thousands of times its original volume and fragment it into tinier pieces so it can hybridise (attach) to a glass slide. Ultimately, she says, a laser reader interprets fluorescing spots on slides into the particular genetic codes present in the sample in each position. Genomic Prediction charges US$1,000 in advance, plus US$400 per embryo analysed. When parents-to-be get the scorecard for their embryos, one of the company’s genetic counsellors talks them through what it means. The head counsellor, Jennifer Eccles, and her team begin by breaking down what the scores for overall health include. They may also address specific risks tied to family histories of disease. In general, though, the early adopters who come their way are often less concerned about a specific disease and more about maximum data-gathering, she says. She calls this frame of mind “genetic forward”. Woman who used IVF criticised by men for giving children ‘incomplete family’ That certainly describes Collins and her husband. Both are authors whose education non-profit, the Collins Institute for the Gifted, promotes individualised teaching programmes for homeschool and boarding-school kids. They live in Pennsylvania with their two sons and want a big family. By the time they heard of polygenic risk scoring, they had spent US$20,000 a pop on five sets of IVF treatments. “We actually did a new round of IVF after having already done five rounds just to get these tests,” Collins says. “That’s how desperately we wanted this data.” They scrimped over months for treatments to generate many embryos and asked Genomic Prediction to analyse a dozen of them. Along with an overall health score, each embryo received a specific score rating its risk for both types of diabetes, several types of cancer, four heart-related conditions and schizophrenia. Genomic Prediction told them one of their embryos had a 1.61 per cent chance of schizophrenia, compared with a 1 per cent risk in the general population, while another embryo had just a 0.29 per cent risk. Such data is useful not just for selection, Collins says, but for what many would consider an unusual style of parenting. “When you tell your kid not to smoke pot, it becomes a lot more meaningful when you can say, ‘You, personally, are way more at risk of developing schizophrenia than the general population,’” she says. “It’s about helping kids understand where they need to be careful.” That wasn’t, however, where Collins and her husband wanted to stop. “What was most important to us was mental health and performance,” she says. “We have a lot more confidence in things like early cancer detection and treatment than in the ability to address things like brain fog and depression.” How teachers can recognise signs of anxiety and depression in students Genomic Prediction doesn’t offer scores on cognitive function or height. It originally considered including findings on whether an embryo was likely to be intellectually disabled or in the bottom 1 per cent for height but dropped the idea. So the Collinses downloaded the raw embryo data from Genomic Prediction and exported it to the website of SelfDecode, a Florida company that analyses adult DNA, which they paid US$199 to use for a month. Running the SelfDecode analysis on each of their embryos gave them assessments of far less tangible qualities, such as supposed capacity for stress management. They created a spreadsheet with each embryo’s scores, weighting them according to their desired mental health traits. Many differences were minuscule, but there were some outliers, according to the SelfDecode analysis. It rated one embryo with a 91 per cent risk for chronically low mood, compared with a 21 per cent risk for another. All the cross-checking made the decision much easier, Collins says, because their top pick in terms of SelfDecode’s mental health assessment was also the embryo with the best Genomic Prediction scores for general health. Collins says she and her husband didn’t seek to select against attention-deficit/hyperactivity disorder or autism because the conditions can correlate with some advantages, including raw intelligence. “We’re a very neuro-atypical household,” says Collins, who’s been diagnosed with autism , as has one of her sons. “We feel like the world as it exists now is actually in some cases better adapted for autistic people.” View this post on Instagram A post shared by SelfDecode (@selfdecode) Genomic Prediction doesn’t encourage parents to seek outside insights on non-medical traits, Tellier says, but it is each customer’s right to have access to their embryos’ raw genetic data. He also wouldn’t discount the possible value of other correlations. “A genome is a genome,” he says. “Almost any analysis is possible.” That includes analyses that raise more complex dilemmas. Studies suggest, for example, that higher odds of creativity correlate with higher odds for bipolar disorder. “Reducing the risk for one thing can also reduce the risk for good things that come with it,” says Eccles. “There’s a whole Pandora’s box we have yet to touch.” Polygenic risk scoring is unlikely to face serious legal blowback in the US, where it would be generous to call the regulation of fertility treatments laissez-faire. That leaves parents-to-be vulnerable to companies that overpromise, says Michelle Meyer, a legal scholar and bioethicist at Geisinger Health System, in Pennsylvania. “At a minimum, you want people to know what they’re getting into,” she says. Critics of polygenic embryo testing argue that it could add unnecessary stress and confusion to the already difficult IVF process, leading parents to discard embryos unnecessarily. This spring, the non-profit European Society of Human Genetics called polygenic risk scoring “premature at best”, noting that environment can dramatically affect genetic expression. It said more research is needed to understand how polygenic risk scores might be useful in medical treatment, including for adults. “It will be vital that a societal debate takes place before any potential application of the technique,” the group wrote, “and this should be focused on what would be considered acceptable with regard to the selection of individual traits, in particular.” I do not believe that law or social norms are going to stop parents from giving their kids advantages Simone Collins In other words, the writers weren’t sure about the accuracy of the results but were nonetheless worried about eugenics-style selection – a concern The New England Journal of Medicine also flagged in a call for “an urgent society-wide conversation” on the subject last summer. Treff says he’s game for broader debate. “It does require these big conversations,” he says. “There’s a lot of work there.” In the May issue of Fertility and Sterility , he and Oxford ethicist Julian Savulescu argue that the real crime would be not offering their scores to everyone, because a lower chance of disease means a better life for a future child. “The lesson of the Nazi eugenics programme is that couples, not the State, should make their decisions about reproduction,” they wrote. In December, Genomic Prediction doubled its venture funding to about US$25 million and says it will use the cash to expand and add to its testing panel. Boston IVF, one of the biggest fertility networks in the US, recently started offering Genomic Prediction’s polygenic testing to its patients, says CEO David Stern. “Like anything else, you have early adopters,” he says. “We have had patients who worked in the biotech field or the Harvard milieu who came in and asked for it.” Stern predicts that, like egg freezing, polygenic embryo testing will grow slowly at first, but steadily, and eventually demand will reflect the powerful appeal of lowering a child’s odds for disease. Chinese documentary offers insight into pregnancy pressures placed on women The technology’s potential to exacerbate inequality isn’t lost on him. He already sees the gaps between a state such as Massachusetts, where fertility treatments are often covered by insurance, and California, where they often aren’t. “That’s not fair,” he says, “and the same applies to this, where you create the potential that people who can afford it can now have children without this disease, but people who can’t afford it, can’t.” The analysis also might not be as reliable for non-white people, because genomic data collected to date has tended to skew heavily towards people with European ancestry. Believers such as Collins and her husband support government subsidies for fertility and parenthood but aren’t interested in any conversation about slowing down. “This is about the people who care about giving their children every opportunity,” she says. “I do not believe that law or social norms are going to stop parents from giving their kids advantages.”