Genetic screening and democracy: lessons from debating genetic screening criteria in the Netherlands

Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor’s office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When prenatal screening for all pregnant women became conceivable, the potential increase in scale made social and ethical concerns relevant for the whole of society. Whereas genetic testing in clinical genetic practice was widely accepted, prenatal screening at a population level met with unease. Concerns were raised regarding social pressure to screen: the sum of individual choice might result in a ‘collective eugenics’. The government’s involvement also raised suspicion: actively offering screening evoked associations with eugenic population policies from the first half of the 20th century. By reconstructing elements of policy and public debate on prenatal screening in the Netherlands from the past 30 years, this article discusses how the government has gradually changed its role in balancing the interest of the individual and the collective on genetic reproductive issues. Against a background of increasing knowledge about and demand for prenatal screening among the population, governmental policy changed from focusing on protection by banning screening toward facilitating screening in a careful and ethically sound way by providing adequate information, decision aids and quality assessment instruments. In the meanwhile, invigorating democracy in public debate may entail discussing concepts of ‘the good life’ in relation to living with or without impairments and dealing with genetic information about oneself or one’s offspring

Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections

BACKGROUNDHuntington's disease (HD) is an autosomal dominant neurodegenerative late onset disorder. This review of reproductive options aims to increase reproductive confidence and to prevent suffering in relation to family planning around HD and possibly other late onset neurodegenerative disorders.METHODSSelected relevant literature and own views and experiences as clinical geneticists, psychologists and ethicists have been used.RESULTSPossible options, with emphasis on prenatal diagnosis (PD) and preimplantation genetic diagnosis (PGD) to prevent the transmission of HD to the next generation, are described and discussed. They are formally presented in a decision tree, taking into account the presence or absence of a fully penetrant allele (FPA), a reduced penetrant allele (RPA) or an intermediate allele (IA). A table compares invasive and non-invasive PD and PGD. From a psychological perspective, the complex process of counselling and decision-making regarding reproductive options is discussed. Special attention is paid to the decision to avoid the transmission of the mutation and to the confrontation and coping of a mutation-free child growing up with a parent developing disease symptoms. From an ethical point of view, reflections on both PD and PGD are brought forward taking into account the difference between FPA, RPA and IA, direct testing or exclusion testing and taking into account the welfare of the child in the context of medically assisted reproduction.CONCLUSIONRecommendations and suggestions for good clinical practice in the reproductive care for HD families are formulated.status: publishe

Modelling human embryogenesis : embryo-like structures spark ethical and policy debate

BACKGROUND: Studying the human peri-implantation period remains hindered by the limited accessibility of the in vivo environment and scarcity of research material. As such, continuing efforts have been directed towards developing embryo-like structures (ELS) from pluripotent stem cells (PSCs) that recapitulate aspects of embryogenesis in vitro. While the creation of such models offers immense potential for studying fundamental processes in both pre- and early post-implantation development, it also proves ethically contentious due to wide-ranging views on the moral and legal reverence due to human embryos. Lack of clarity on how to qualify and regulate research with ELS thus presents a challenge in that it may either limit this new field of research without valid grounds or allow it to develop without policies that reflect justified ethical concerns. OBJECTIVE AND RATIONALE: The aim of this article is to provide a comprehensive overview of the existing scientific approaches to generate ELS from mouse and human PSCs, as well as discuss future strategies towards innovation in the context of human development. Concurrently, we aim to set the agenda for the ethical and policy issues surrounding research on human ELS. SEARCH METHODS: The PubMed database was used to search peer-reviewed articles and reviews using the following terms: 'stem cells', 'pluripotency', 'implantation', 'preimplantation', 'post-implantation', 'blastocyst, 'embryoid bodies', 'synthetic embryos', 'embryo models', 'self-assembly', 'human embryo-like structures', 'artificial embryos' in combination with other keywords related to the subject area. The PubMed and Web of Science databases were also used to systematically search publications on the ethics of ELS and human embryo research by using the aforementioned keywords in combination with 'ethics', 'law', 'regulation' and equivalent terms. All relevant publications until December 2019 were critically evaluated and discussed. OUTCOMES: In vitro systems provide a promising way forward for uncovering early human development. Current platforms utilize PSCs in both two- and three-dimensional settings to mimic various early developmental stages, including epiblast, trophoblast and amniotic cavity formation, in addition to axis development and gastrulation. Nevertheless, much hinges on the term 'embryo-like'. Extension of traditional embryo frameworks to research with ELS reveals that (i) current embryo definitions require reconsideration, (ii) cellular convertibility challenges the attribution of moral standing on the basis of 'active potentiality' and (iii) meaningful application of embryo protective directives will require rethinking of the 14-day culture limit and moral weight attributed to (non-)viability. Many conceptual and normative (dis)similarities between ELS and embryos thus remain to be thoroughly elucidated. WIDER IMPLICATIONS: Modelling embryogenesis holds vast potential for both human developmental biology and understanding various etiologies associated with infertility. To date, ELS have been shown to recapitulate several aspects of peri-implantation development, but critically, cannot develop into a fetus. Yet, concurrent to scientific innovation, considering the extent to which the use of ELS may raise moral concerns typical of human embryo research remains paramount. This will be crucial for harnessing the potential of ELS as a valuable research tool, whilst remaining within a robust moral and legal framework of professionally acceptable practices

The 'thousand-dollar genome': an ethical exploration

Sequencing an individual's complete genome is expected to be possible for a relatively low sum ‘one thousand dollars' within a few years. Sequencing refers to determining the order of base pairs that make up the genome. The result is a library of three billion letter combinations. Cheap whole-genome sequencing is of greatest importance to medical scientific research. Comparing individual complete genomes will lead to a better understanding of the contribution genetic variation makes to health and disease. As knowledge increases, the ‘thousand-dollar genome' will also become increasingly important to healthcare. The applications that come within reach raise a number of ethical questions. This monitoring report addresses the issue