A special report published in the New England Journal of Medicine raises serious questions about the benefits, risks and ethics of a new service — which the authors call “embryo selection based on polygenic scores,” or ESPS. The service allows in vitro fertilization patients to select embryos with the goal of choosing healthier and even smarter children.
In the report “Problems with Using Polygenic Scores to Select Embryos,” the multinational team of researchers describes the limitations of the service. They also warn that patients, and even in vitro fertilization clinicians, may think that the service is more effective and less risky than it is.
The authors highlight that since the same gene often influences many different traits, selecting for one trait can lead to the unintentional selection of adverse traits. They also warn that using the service has the potential to alter population demographics, exacerbate socioeconomic inequalities and devalue certain traits.
If ESPS continues to be available to IVF patients, the researchers call on the U.S. Federal Trade Commission to develop and enforce standards for responsible communication about the service. The authors also call for a society-wide conversation about the ethical use of the technology and whether it should be regulated.
An imperfect way to ensure healthy children
Polygenic scores are predictions of individual health and other outcomes derived from studies of the genome. In adults, polygenic scores have been shown to partially predict those outcomes. However, their predictive power is significantly reduced when comparing embryos to one another, the report authors explain.
“Polygenic scores are already only weak predictors for most individual adult outcomes, especially for social and behavioral traits, and there are several factors that lower their predictive power even more in the context of embryo selection,” said Patrick Turley, assistant professor (research) of economics at the USC Dornsife College of Letters, Arts and Sciences and co-first author of the paper. “Polygenic scores are designed to work in a different setting than an IVF clinic. These weak predictors will perform even worse when used to select embryos.”
Turley, who is also director of the Behavioral and Health Genomics Center at the USC Dornsife Center for Economic and Social Research, and his colleagues on the study examined if ESPS is any more effective at ensuring future health than random selection of embryos. To do so, they modeled the expected difference in a future individual’s risk for several diseases, comparing the use of ESPS to select an embryo versus choosing one viable embryo at random from among 10. They found that, in most cases, the reduction of disease risk the service offers is very small and highly uncertain.
Multiple companies are now working with IVF clinics to offer the service to patients who want to select an embryo with a lower chance of growing up to develop diabetes, cancer, heart disease, Alzheimer’s disease, inflammatory bowel disease and schizophrenia. One company also offers the service for the purpose of selecting embryos according to their predicted educational attainment, household income and cognitive ability. The founder of another company has not ruled out someday offering ESPS in some countries to choose skin color or above-average mental ability.
Drawbacks to the selection service
For ESPS to work, polygenic scores need to give at least moderately accurate predictions of whether the selected embryos will end up developing a certain trait or not. The studies that generate the polygenic scores sometimes suggest moderate or even large differences in actual outcomes between people with high versus low scores, but those differences are based on a sample of people from different families. As Turley and colleagues note, ESPS usually involves comparing members of the same family, which significantly lowers its predictive power.
Additionally, the studies that produce polygenic scores involve people with similar ancestries and mostly European ancestries. As a result, most polygenic scores constructed today will be less predictive for people of other ancestries.
Finally, assessments of the predictive power of polygenic scores typically assume very similar environments for the generation enrolled in the original study and the generation that will be born as a result of ESPS. But by the time an embryo selected by the service is an adult, the person may face a very different environment.
Widespread use of ESPS raises other risks, as well. For instance, the researchers warn that use of the service could exacerbate existing health and other disparities, as it is largely only accessible to the relatively wealthy and it currently works best among those with European ancestries. It might also amplify prejudice and discrimination by signaling that existing people with traits that parents select against are less valuable.
“Some countries have authorities that decide which traits embryos can be tested for,” said Michelle N. Meyer, assistant professor of bioethics and a legal scholar at Geisinger Health System and co-first author of the special report. “But in the U.S., there is a strong legal and ethical tradition of viewing reproductive decisions as matters of private individual choice. In the short term, the FTC should help establish what counts as adequate evidence to support claims about the expected benefits of ESPS and what counts as adequate information disclosure in this context.”
The researchers also call for professional medical societies to develop policies and guidance and for companies themselves to demonstrate that the information they provide to diverse customers is complete, accurate and well-understood.
They also say there needs to be a society-wide conversation about whether existing legal frameworks can adequately ensure accurate information about ESPS, and if limits on the use of the service should be adopted.
“Many individual reproductive decisions, aggregated over generations, can have profound societal consequences,” said Daniel J. Benjamin, corresponding author and a professor at the UCLA Anderson School of Management and David Geffen School of Medicine. “Collectively, these decisions could alter population demographics, exacerbate inequalities and devalue traits that are selected against.”
About the study
In addition to Turley, Meyer and Benjamin, authors on the study include Nancy Wang of the National Bureau of Economic Research; David Cesarini of New York University; Evelynn Hammonds and David Laibson of Harvard University; Alicia R. Martin, Ben M. Neale and Heidi L. Rehm of the Broad Institute of Harvard and MIT; Louise Wilkins-Haug of Harvard Medical School; Steven Hyman, M.D., Harvard University and Broad Institute of Harvard and MIT; and Peter M. Visscher of the University of Queensland, Australia.
The research was supported by the National Institutes of Health, Open Philanthropy, the Ragnar Söderberg Foundation, the Pershing Square Fund for Research on the Foundations of Human Behavior, the Robert Wood Johnson Foundation, the Russell Sage Foundation, the JPB Foundation, the National Health and Medical Research Council, the Stanley Family Foundation and the Australian Research Council.
