Genetic testing of embryos has the potential to usher in a new era of human reproductive control. Preimplantation genetic testing (PGT) has been used by couples at risk of having a child with a severe or life-limiting disease such as cystic fibrosis or Duchenne muscular dystrophy for decades to select among embryos created through in vitro fertilization (IVF) for those that do not carry the disease-causing gene. But what new form of genetic testing could persuade healthy, fertile couples to abandon our tried-and-true method of childbirth in favor of hormone shots, egg extractions, and DNA analysis?
Orchid Biosciences, a California-based start-up, claims to have an answer to that question. Prior to conception, the company gives prospective parents genetic testing to create risk scores that estimate their own likelihood of developing common illnesses like heart disease, diabetes, and schizophrenia, as well as the likelihood of passing such hazards on to a future kid. Parents-to-be can then employ IVF, as well as Orchid's future embryo screening package, to determine which of their embryos are the healthiest for a pregnancy.
Orchid intends to employ PGT and IVF to develop what is currently a robust industry for prospective parents' screening tests. Those whose background put them at increased risk for a certain disorder, such as Tay-Sachs disease in the Ashkenazi Jewish population, were the only ones provided testing to avoid genetic sickness in the following generation. In 2010, Counsyl (now part of Myriad Genetics) launched the first universal genetic screen that covered a wide spectrum of disorders. Carrier screening is now a $1.7 billion business. These tests look for genetic disorders that would otherwise only be discovered after the birth of a kid with the disease. The majority of children are born healthy, and the majority of couples who undergo carrier screening feel relieved.
Orchid's risk assessment includes common diseases, ensuring that a large majority of potential parents who undergo this type of preconception testing will discover something to be concerned about. Those who choose to act on their fears will soon be able to pay for IVF along with Orchid's embryo-testing package. According to the company's promotional materials, it will provide a scorecard to identify future children who are least likely to develop heart disease, breast cancer, prostate cancer, type 1 or 2 diabetes, and five other conditions that make up Orchid's current common disease risk portfolio among various embryos.
Orchid breaks new ground by providing the first—but likely not the last—consumer-driven model of human reproduction, with a marketing approach that encourages routine use of IVF for those who can afford it. The objectives of this new Silicon Valley venture into health care have been endorsed by health-tech giants, including Anne Wojcicki, co-founder of 23andMe and an Orchid investor. The "Couple Report," which costs $1,100, is Orchid's debut product on the market. Phase two, which is set to start later this year, evaluates embryos generated through IVF, allowing the couple to select and choose among possible offspring in a process that Orchid CEO Noor Siddiqui referred to as "embryo prioritization" in an interview with the podcast Mendelspod in April. Siddiqui is a former Thiel Foundation Fellow with a focus on the application of technology in medicine. She did not respond to Scientific American's repeated requests for an interview.
Orchid's introduction has been met with suspicion by geneticists, owing to concerns over the company's use of a technique called polygenic risk scores to measure an embryo's lifelong risk of common disorders. Heart disease, like musical skill or height, runs in families, but only in rare situations can the hereditary risk be linked to a particular gene. Hundreds, if not thousands, of genes each have a minor role. Polygenic risk scores aim to summarize the overall chance of a specific outcome—such as developing a disease—by simply noting which patterns of variation in a genome are related with a higher or lower likelihood of developing the illness. To put it another way, this method tells us who is more or less likely to get sick without explaining why. The statistical link is real, but not conclusive, and it follows population-level trends that may or may not be relevant to the individual in question.
Researchers who deal with polygenic risk scores are wary of its application in this situation. "We don't know what these variations are doing biologically," says Peter Kraft, a Harvard T. H. Chan School of Public Health professor of epidemiology and biostatistics.
“Something that’s associated with a decreased risk of breast cancer could be associated with all other kinds of things, some of which might actually increase your risk of something else. We just don’t know enough yet.”
Some form of prenatal planning, such as Orchid's, may be achievable in the future, but few specialists appear to believe that today is that day. The inherent weakness of using polygenic risk scores to distinguish between sibling embryos—which, unlike random individuals in a population, will be identical in 50% of the genetic variation that is examined to generate a score—was highlighted in a special report published in the New England Journal of Medicine on July 1. The paper concluded with advice on how to appropriately communicate any purported benefits from polygenic scores in embryo selection, as well as the importance of emphasizing the data's underlying ambiguities.
Despite Orchid's staunch support for parental autonomy, bioethicists such as Gabriel Lázaro-Muoz of Baylor College of Medicine's Center for Medical Ethics and Health Policy are concerned that Orchid's system of ranking embryos may unduly influence prospective parents and replace a much-needed societal debate on what constitutes a good life. According to Lázaro-Muoz, having these enterprises is detrimental for this reason.
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