Modeling policy development: examining national governance of stem cell-based embryo models.

Researchers can now coax human pluripotent stem cells to imitate the structure and spontaneous self-organization of the developing human embryo. Although these stem cell-based embryo models present an advantageous alternative to embryo research, they also raise ethical and policy challenges. In 2021, the International Society for Stem Cell Research revised its Guidelines for Stem Cell Research and Clinical Translation, providing contemporaneous best practices for ethical conduct in the field. The Guidelines complement national governance frameworks; however, they also contain contentious and aspirational norms that might catalyze change in research practice and in the enactment of national policies. Using a sample of 11 research-intensive countries, the authors compare research policy frameworks against the International Society for Stem Cell Research Guidelines to showcase how developments in global and national policies might affect stem cell-based embryo model research governance and illustrate fertile areas for ethical reflection and policy development.

Following scientific advances, researchers can induce stem cells to model the development of the human embryo with increasing accuracy. The International Society for Stem Cell Research Guidelines for Stem Cell Research and Clinical Translation provide contemporary standards for research on so-called stem cell-based embryo models (SCB-EMs). However, because SCB-EMs are not mentioned in national policies and do not fit neatly into existing regulatory categories, it is unclear how countries intend to regulate them. In this article, the authors compare policy frameworks in 11 research-intensive countries to analyze how the influential Guidelines both complement and catalyze change in national policies. The Guidelines provide specific instructions for assessing and monitoring different kinds of SCB-EM research proposals, serving as a useful reference to bolster open-ended national policy requirements. However, in some areas the Guidelines appear to conflict with national policies governing stem cell and embryo research, reflecting divergent priorities and ethical assessments. Without policy review to address regulatory and ethical uncertainty, researchers may default to adherence to the Guidelines, a global standard that does not necessarily reflect local historic, legal and cultural influences. Evidence from France and Israel indicates that comprehensive legislative review is both useful and can proceed without eroding compromises designed to uphold plural beliefs regarding the moral status of the human embryo. As exemplified in countries such France and Israel, mandated legislative review processes are useful tools that can be deployed in manner that upholds pluralistic beliefs regarding the human embryo's moral status. They can serve as a pathway to re-engage the public and ensure diverse viewpoints are reflected in governance of SCB-EM research, ultimately facilitating public trust in science.

Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Community Health Study/Study of Latinos.

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.

Helping the science speak for itself: lessons learned developing video summaries for a precision medicine and health disparities collaborative.

Skills to effectively communicate research findings are important to expand meaningful inclusion of the public in research, but attempts to summarize findings may be challenging given increasing reliance on succinct communications. Led by our Ethics Advisory Board and within the context of this work with the Precision Medicine and Health Disparities Collaborative, the authors decided to engage in the iterative process of developing video summaries. Our stakeholders taught us to incorporate novel strategies to engage broader audiences, leading to the production of two video summaries, a public summary toolbox and an adapted process for developing video summaries. The authors refreshed the static concept of 'research summaries' and found ways of producing summaries which emphasized a dynamic reframing of the shared benefits of science.

Health communications related to research (like summaries about research studies) are important to the health of diverse communities. It is up to investigators to publicize the findings of their research, and written communications may not be the most effective way of getting the public excited about or interested in science. Our Ethics Advisory Board encouraged us to pursue a more dynamic format to report scientific findings. Led by our Ethics Advisory Board and other investigators of a collaborative precision medicine research center, the authors created two video summaries based on the findings of two research articles. In this article, the authors describe an iterative, stakeholder-centered process of creating video summaries to engage nonscientists in research, and make science more relevant and meaningful to the general public.

Addressing underrepresentation in genomics research through community engagement.

The vision of the American Society of Human Genetics (ASHG) is that people everywhere will realize the benefits of human genetics and genomics. Implicit in that vision is the importance of ensuring that the benefits of human genetics and genomics research are realized in ways that minimize harms and maximize benefits, a goal that can only be achieved through focused efforts to address health inequities and increase the representation of underrepresented communities in genetics and genomics research. This guidance is intended to advance community engagement as an approach that can be used across the research lifecycle. Community engagement uniquely offers researchers in human genetics and genomics an opportunity to pursue that vision successfully, including by addressing underrepresentation in genomics research.

Roles and responsibilities in stem cell research: a focus group study with stem cell researchers and patients.

Background: The perspectives of researchers and patients regarding roles and responsibilities in stem cell research are rarely studied, but these could offer insights about responsible research conduct. Method: We have conducted a qualitative study consisting of focus groups with both early- (n = 7) and late-career stem cell researchers (n = 11) that are primarily based in Europe, and with Dutch patients with chronic lower back pain (n = 9). These focus groups have been analyzed thematically. Results: Four themes were identified: 1) roles and responsibilities in the laboratory, 2) responsibilities of and toward patients and the public, 3) the role of regulation and 4) structural hurdles for responsibility. Discussion: The results suggest that responsible research conduct could be improved by addressing grant application procedures, publication pressure and by providing support of dissemination activities for researchers. Conclusion: Responsibility in stem cell research could be enhanced by embracing open science initiatives and targeted training.

What researchers and patients think about roles and responsibilities in stem cell research is not well known, but this information could help to deal with the ethical aspects of stem cell research. We have conducted focus groups with early and late career stem cell researchers based in Europe and with Dutch patients. Four overarching themes were identified: 1) roles and responsibilities in the laboratory, 2) responsibilities of and toward patients and the public, 3) the role of regulation and 4) structural hurdles for responsibility. The results suggest that responsible research conduct could be improved by addressing grant application procedures, publication pressure and by providing support for communicating the progress and results of research. More generally, open science initiatives and targeted training could help to improve dealing with the ethical aspects of stem cell research.

Streamlining ethics review for international health research.

Single-site review means protection and efficiency.

Recognizing the ethical implications of stem cell research: A call for broadening the scope.

The ethical implications of stem cell research are often described in terms of risks, side effects, safety, and therapeutic value, which are examples of so-called hard impacts. Hard impacts are typically measurable and quantifiable. To understand the broader spectrum of ethical implications of stem cell research on science and society, it is equally important to recognize soft impacts. Soft impacts are the effects on behavior, experiences, actions, moral values, and social structures; these are often indirect effects of stem cell research. The combined notions of hard and soft impacts offer a broader way of thinking about the social and ethical implications of stem cell research and can help to steer stem cell research into a sociable desirable direction. Soft impacts enable researchers to become more aware of the broad range of significant implications involved in their work and deserve equal attention for understanding such ethical and societal effects of stem cell research.

ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update.

The International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here.

Author Correction: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.

Ethical, legal, and social issues (ELSI) in rare diseases: a landscape analysis from funders.

Recent interest in personalized medicine has highlighted the importance of research in ethical, legal, and social issues (ELSI). Issues in ELSI research may be magnified in the rare diseases population (i.e., small numbers of affected individuals, challenges in maintaining confidentiality, and paucity of treatments for diseases where natural history information may be limited). More than other areas of research, potential barriers include the lack of funding opportunities and appropriate review processes for applications to funding agencies. The ELSI Working Group of the International Rare Diseases Research Consortium (IRDiRC) performed an informal survey on ELSI funding initiatives to learn more about different funding mechanisms and to identify potential gaps in funding opportunities. The Working Group discusses these challenges and highlights the role of funding agencies and partners such as patient advocacy groups, specialists in social sciences and humanities, and clinicians to advance ELSI research in rare diseases.

Regulating Preimplantation Genetic Testing across the World: A Comparison of International Policy and Ethical Perspectives.

Preimplantation genetic testing (PGT) is a reproductive technology that, in the course of in vitro fertilization (IVF), allows prospective parents to select their future offspring based on genetic characteristics. PGT could be seen as an exercise of reproductive liberty, thus potentially raising significant socioethical and legal controversy. In this review, we examine-from a comparative perspective-variations in policy approaches to the regulation of PGT. We draw on a sample of 19 countries (Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Singapore, South Korea, Switzerland, United Kingdom, and the United States) to provide a global landscape of the spectrum of policy and legislative approaches (e.g., restrictive to permissive, public vs. private models). We also explore central socioethical and policy issues and contentious applications, including permissibility criteria (e.g., medical necessity), nonmedical sex selection, and reproductive tourism. Finally, we further outline genetic counseling requirements across policy approaches.

Model consent clauses for rare disease research.

BACKGROUND: Rare Disease research has seen tremendous advancements over the last decades, with the development of new technologies, various global collaborative efforts and improved data sharing. To maximize the impact of and to further build on these developments, there is a need for model consent clauses for rare diseases research, in order to improve data interoperability, to meet the informational needs of participants, and to ensure proper ethical and legal use of data sources and participants' overall protection. METHODS: A global Task Force was set up to develop model consent clauses specific to rare diseases research, that are comprehensive, harmonized, readily accessible, and internationally applicable, facilitating the recruitment and consent of rare disease research participants around the world. Existing consent forms and notices of consent were analyzed and classified under different consent themes, which were used as background to develop the model consent clauses. RESULTS: The IRDiRC-GA4GH MCC Task Force met in September 2018, to discuss and design model consent clauses. Based on analyzed consent forms, they listed generic core elements and designed the following rare disease research specific core elements; Rare Disease Research Introductory Clause, Familial Participation, Audio/Visual Imaging, Collecting, storing, sharing of rare disease data, Recontact for matching, Data Linkage, Return of Results to Family Members, Incapacity/Death, and Benefits. CONCLUSION: The model consent clauses presented in this article have been drafted to highlight consent elements that bear in mind the trends in rare disease research, while providing a tool to help foster harmonization and collaborative efforts.

The clinical application of gene editing: ethical and social issues.

Gene-editing techniques have progressed rapidly in the past 5 years. There are already ongoing human somatic gene-editing clinical trials for multiple diseases. And there has been one purported scenario of human germline gene editing in late 2018. In this paper, we will review the current state of the technology, discuss the ethical and social issues that surround the various forms of gene editing, as well as review emerging stakeholder data from professionals, the 'general public' and individuals and families dealing with genetic diseases potentially treatable by gene editing.