Three models for the regulation of polygenic scores in reproduction

Abstract

The past few years have brought significant breakthroughs in understanding human genetics. This knowledge has been used to develop ‘polygenic scores’ (or ‘polygenic risk scores’) which provide probabilistic information about the development of polygenic conditions such as diabetes or schizophrenia. They are already being used in reproduction to select for embryos at lower risk of developing disease. Currently, the use of polygenic scores for embryo selection is subject to existing regulations concerning embryo testing and selection. Existing regulatory approaches include ‘disease-based' models which limit embryo selection to avoiding disease characteristics (employed in various formats in Australia, the UK, Italy, Switzerland and France, among others), and 'laissez-faire' or 'libertarian' models, under which embryo testing and selection remain unregulated (as in the USA). We introduce a novel 'Welfarist Model' which limits embryo selection according to the impact of the predicted trait on well-being. We compare the strengths and weaknesses of each model as a way of regulating polygenic scores. Polygenic scores create the potential for existing embryo selection technologies to be used to select for a wider range of predicted genetically influenced characteristics including continuous traits. Indeed, polygenic scores exist to predict future intelligence, and there have been suggestions that they will be used to make predictions within the normal range in the USA in embryo selection. We examine how these three models would apply to the prediction of non-disease traits such as intelligence. The genetics of intelligence remains controversial both scientifically and ethically. This paper does not attempt to resolve these issues. However, as with many biomedical advances, an effective regulatory regime must be in place as soon as the technology is available. If there is no regulation in place, then the market effectively decides ethical issues.

Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations

“…These technologies are likely to dramatically advance and achieve broad utilization in the coming years. A strong case can be made that patients will benefit significantly from these developments, but the associated ethical issues deserve serious attention, as exemplified in the work of Professor Julian Savulescu-Director of the Oxford Uehiro Centre for Practical Ethics-and collaborators [4]. We hope that this article is the beginning of a far-reaching conversation between scientists, ethicists, medical professionals, and broader society.…”

“…Indeed, some of the technologies that were deemed "ethically dubious" when first introduced (such as IVF itself, as well as aneuploidy screening) were, over time, incorporated into routine IVF practice. It is not within the ambit of this paper to provide the range of potential ethical deliberations for PGT-P, and this has been endeavored elsewhere [4]. However, it is important to recognize the pillars of medical ethics for the introduction of new technologies, especially those that can have ongoing generational impacts: autonomy, beneficence, non-maleficence, and justice.…”

“…As already mentioned, we do not attempt a comprehensive discussion of all of the ethical issues raised by IVF polygenic screening. For that, we refer the reader to the recent article "Three models for the regulation of polygenic scores in reproduction" by Munday and Savalescu [4]. An incomplete list of the topics investigated there includes the impact of PGT-P on inequality, selection on non-medical traits, such as cosmetic traits or cognitive ability, impact on genetic diversity, effect on parent-child relationships, and potential regulatory structures.…”

“…We also discuss related ethical issues, although a full discussion of these would require a much longer paper. Indeed, an in-depth review was recently published by Professor Julian Savulescu-Director of the Oxford Uehiro Centre for Practical Ethics-and collaborators [4], which we discuss below. Our purpose is to make bioethicists and philosophers more aware of recent scientific and technological breakthroughs (i.e., the current research frontier and state of the art), as well as to inform medical genomics and IVF researchers of some ethical perspectives.…”

Utility of polygenic embryo screening for disease depends on the selection strategy

“…Another potential application of PRSs is preimplantation screening of in vitro fertilization (IVF) embryos, or polygenic embryo screening (PES). Polygenic embryo screening has been offered since 2019 (Treff, Eccles, et al, 2019), but has been the focus of comparatively little empirical research, despite debate over ethical and social concerns surrounding the practice (Anomaly, 2020;Lázaro-Muñoz et al, 2020;Munday & Savulescu, 2021).…”