iPS cells: mapping the policy issues.

Given the explosion of research on induced pluripotent stem (iPS) cells, it is timely to consider the various ethical, legal, and social issues engaged by this fast-moving field. Here, we review issues associated with the procurement, basic research, and clinical translation of iPS cells.

Evaluating standards for 'serious' disease for preimplantation genetic testing: a multi-case study on regulatory frameworks in Japan, the UK, and Western Australia.

BACKGROUND: A number of countries are leading the way in creating regulatory frameworks for preimplantation genetic testing (PGT). Among these countries, a point of consensus is that PGT may be used to avoid the birth of a child with a serious genetic disease. However, standards for evaluating disease severity in this context are not always clear. Considering the numerous medical and social implications of defining a standard for serious disease, our study sought out to better understand how disease severity for PGT is being defined by analyzing and comparing the regulatory landscapes for PGT in various countries. METHODS: We carried out a multi-case study analysis using policy documents from the UK, Western Australia, and Japan. Documentary analysis was used to analyze and compare these documents in terms of medical indications for PGT, evaluation methods of applications for PGT, and review frameworks used during the evaluation process, which includes the specific medical and social factors that are considered. RESULTS: Within our three case studies, medical indications for PGT are based on an estimated risk of the woman giving birth to a child with a genetic abnormality with known clinical deficits. Evaluation methods for approving applications for PGT include reference to a pre-approved list of genetic conditions (the UK) and case-by-case reviews (all case studies). Review frameworks for case-by-case reviews include reference to a list of considered factors (the UK and Western Australia) and a definition statement of disease severity (Japan), which provide insight into interpretations of disease severity in each context. CONCLUSIONS: The results of this study point to the possible medical and social impacts of PGT regulatory frameworks on multiple stakeholders. Furthermore, it suggests that impacts in this case are not only caused by whether PGT is permitted or not, but also by the circumstances under which it is allowed and how decisions regarding its approval are made. Our results may serve as valuable insights for countries that already have established policy for PGT but are considering revision, countries that are without policy, and for discussions on related genetic and reproductive technologies.

Framework and Practical Guidance for the Ethical Use of Electronic Methods for Communication With Participants in Medical Research.

Online communication with participants, including online recruitment, electronic informed consent, and data communication, is one of the fields to which information and communication technology (ICT) has been applied in medical research. Online communication provides various benefits, especially for genome research and rare disease research. However, ethical challenges that are derived from or exacerbated by online communication need to be addressed. Here, we present an overview of such ethical issues and provide practical guidance for the ethical implementation of ICT. We specify the ethical issues in the context of using online communication for medical research by an analysis based on the eight ethical principles for clinical research. Informed by this ethical context, we then develop a novel framework for the governance of medical research involving ICT, which consists of eight categories: five research processes (ie, design of research, recruitment, informed consent, data communication, and dissemination and return of results) and three overarching perspectives related to multiple processes of research (ie, access to research and online dialog, community involvement, and independent review). Finally, we present a practical guidance chart for researchers, patient partners, independent reviewers, and funding agencies. We believe that our study will contribute to the ethical implementation of online communication in medical research.

Superionic Ag+ Conductor Ag17(CO3)3I11.

A new superionic Ag+ conductor with a nominal composition Ag17(CO3)3I11 (11AgI-3Ag2CO3) was found in the AgI-Ag2CO3 system. The conductor, which was formed at temperatures from 100 to 170 °C, is a metastable phase that gradually decomposes into AgI and Ag10(CO3)I4 over a period of a few weeks at room temperature (RT). A Ag+ ionic conductivity of 0.16 S/cm was measured at RT, and an activation energy of 0.33 eV was evaluated in the temperature range from -9 to 19 °C. Single-crystal X-ray analysis revealed that Ag17(CO3)3I11 crystallized in a rhombohedral unit cell with hexagonal parameters of a = 15.8831(6) Å and c = 30.0730(13) Å at -183 °C and space group R3c. The Ag atoms were distributed over 53 sites in the asymmetry unit, with a maximum occupancy of 0.33(8). The continuous distribution of the partially occupied Ag sites was associated with the conduction paths of the Ag+ ions in the structure.

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

A proposal on the first Japanese practical guidance for the return of individual genomic results in research settings.

Large-scale, low-cost genome analysis has become possible with next-generation sequencing technology, which is currently used in research and clinical practice. Many attempts of returning individual genomic results have commenced not only in clinical practice, but also in research settings of several countries. In Japan, the government guidelines include a section on the disclosure of genetic information regarding genome analysis in research. However, no practical guidance for the return of individual genomic results in research settings (ROGRR) currently exists. We propose practical guidance regarding ROGRR in Japan based on extensive research, including a literature review of related previous studies, an examination of the relevant legislation in Japan, and interviews with stakeholders. The guidance we developed consists of "Points to consider" and "Issues for further discussion and consideration." The "Points to consider" were divided into five parts, from preliminary review before discussion of policy, to the actual return and follow-up process, in the order of the assumed ROGRR process. It is anticipated that a situation will arise where numerous research projects will consider ROGRR carefully and realistically in the future, and in the process of drafting such practical guidance, various issues requiring continuous discussion will emerge. The necessities of continuous discussion concerning ROGRR in Japan's context is increasing, particularly in terms of the ethical, legal, and social implications. We believe such discussions and considerations may contribute to creating a new system that will increase availability of personalized medicine and prevention using genetic information, allowing them to become useful to the broader population.

Landscape of Participant-Centric Initiatives for Medical Research in the United States, the United Kingdom, and Japan: Scoping Review.

BACKGROUND: Information and communication technology (ICT) has made remarkable progress in recent years and is being increasingly applied to medical research. This technology has the potential to facilitate the active involvement of research participants. Digital platforms that enable participants to be involved in the research process are called participant-centric initiatives (PCIs). Several PCIs have been reported in the literature, but no scoping reviews have been carried out. Moreover, detailed methods and features to aid in developing a clear definition of PCIs have not been sufficiently elucidated to date. OBJECTIVE: The objective of this scoping review is to describe the recent trends in, and features of, PCIs across the United States, the United Kingdom, and Japan. METHODS: We applied a methodology suggested by Levac et al to conduct this scoping review. We searched electronic databases-MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase (Excerpta Medica Database), CINAHL (Cumulative Index of Nursing and Allied Health Literature), PsycINFO, and Ichushi-Web-and sources of grey literature, as well as internet search engines-Google and Bing. We hand-searched through key journals and reference lists of the relevant articles. Medical research using ICT was eligible for inclusion if there was a description of the active involvement of the participants. RESULTS: Ultimately, 21 PCIs were identified that have implemented practical methods and modes of various communication activities, such as patient forums and use of social media, in the field of medical research. Various methods of decision making that enable participants to become involved in setting the agenda were also evident. CONCLUSIONS: This scoping review is the first study to analyze the detailed features of PCIs and how they are being implemented. By clarifying the modes and methods of various forms of communication and decision making with patients, this review contributes to a better understanding of patient-centric involvement, which can be facilitated by PCIs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.7407.

Public attitudes in Japan toward participation in whole genome sequencing studies.

BACKGROUND: Recent innovations in gene analysis technology have allowed for rapid and inexpensive sequencing of entire genomes. Thus, both conducting a study using whole genome sequencing (WGS) in a large population and the clinical application of research findings from such studies are currently feasible. However, to promote WGS studies, understanding and voluntary participation by the general public is needed. Therefore, it is essential to investigate the general public's attitude toward and understanding of WGS studies. The primary goal of our research is to investigate these issues and to discover how they relate to research participation in WGS studies. METHODS: A survey of awareness regarding WGS and studies using WGS was conducted with a sample of 2000 or more participants using a self-administered questionnaire posted on the Internet between February 20 and 21, 2015. Prior to the survey, we briefly explained WGS and WGS study-related issues to the respondents in order to provide them with the minimum knowledge required to answer the questionnaire. We then conducted an analysis, including cross-classification. RESULTS: For the question regarding interest in WGS, 46.6% of participants responded "Yes." 70.7% of all respondents said that they were interested in some kinds of findings that could be obtained from WGS studies. Regarding participation in WGS studies, 29.0% were interested in participating. The demographic factors significantly related to attitudes toward research participation were age, level of education, and employment status. The results also suggest that concerns about WGS have a positive effect on people's willingness to participate. Furthermore, it was shown that for people who were not interested in their gene-related information, concerns about WGS negatively impacted their willingness to participate. However, for people who were interested in their gene-related information, their concerns might not have impacted their willingness to participate. DISCUSSION AND CONCLUSIONS: This research has shown several key factors that affect the willingness of the general public for the participation to the WGS studies. One of the unexpected findings is that concerns toward WGS studies generally have positive effect on the peoples' attitude. It will be interesting to further investigate into the various types of concerns that people in different groups have about WGS.

Including all voices in international data-sharing governance.

BACKGROUND: Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in research, as well as reducing waste and promoting transparency. As this approach gains momentum, these data-sharing practices have implications for many kinds of research as they become standard practice across the world. MAIN TEXT: The governance frameworks that have been developed to support biomedical research are not well equipped to deal with the complexities of international data sharing. This system is nationally based and is dependent upon expert committees for oversight and compliance, which has often led to piece-meal decision-making. This system tends to perpetuate inequalities by obscuring the contributions and the important role of different data providers along the data stream, whether they be low- or middle-income country researchers, patients, research participants, groups, or communities. As research and data-sharing activities are largely publicly funded, there is a strong moral argument for including the people who provide the data in decision-making and to develop governance systems for their continued participation. CONCLUSIONS: We recommend that governance of science becomes more transparent, representative, and responsive to the voices of many constituencies by conducting public consultations about data-sharing addressing issues of access and use; including all data providers in decision-making about the use and sharing of data along the whole of the data stream; and using digital technologies to encourage accessibility, transparency, and accountability. We anticipate that this approach could enhance the legitimacy of the research process, generate insights that may otherwise be overlooked or ignored, and help to bring valuable perspectives into the decision-making around international data sharing.

Analysis of an ADTKD family with a novel frameshift mutation in MUC1 reveals characteristic features of mutant MUC1 protein.

BACKGROUND: Medullary cystic kidney disease Type 1 is an autosomal dominant tubulointerstitial kidney disease (ADTKD). Recently, mucin 1 (MUC1) was identified as a causal gene of medullary cystic kidney disease (ADTKD-MUC1). However, the MUC1 mutation was found to be a single cytosine insertion in a single copy of the GC-rich variable number of tandem repeats (VNTRs), which are very difficult to analyze by next-generation sequencing. To date, other mutations have not been detected in ADTKD-MUC1, and the mutant MUC1 protein has not been analyzed because of the difficulty of genetically modifying the VNTR sequence. METHODS: We conducted whole-exome analyses of an ADTKD family by next-generation sequencing. We also performed histopathological analyses of a renal biopsy from a pedigree family member. We constructed a mutant protein expression vector based on the patient genome sequence and characterized the nature of the mutant protein. RESULTS: We found a novel frameshift mutation before the VNTR in the MUC1 gene. The resulting mutant MUC1 protein had a very similar amino acid sequence and predicted 3D structure to the previously reported mutant protein. Notably, the recombinant mutant MUC1 protein was trapped in the cytoplasm and appeared to self-aggregate. The patient native mutant protein was also found in urine exosomes. CONCLUSIONS: This novel frameshift mutation in the MUC1 gene and consequent mutant protein may contribute to the future discovery of the pathophysiology of ADTKD-MUC1. The mutant MUC1 protein in urine exosomes may be used for non-DNA-related diagnosis.

Reflections on the cost of "low-cost" whole genome sequencing: framing the health policy debate.

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.

International network of cancer genome projects.

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Using digital technologies to engage with medical research: views of myotonic dystrophy patients in Japan.

BACKGROUND: As in other countries, the traditional doctor-patient relationship in the Japanese healthcare system has often been characterised as being of a paternalistic nature. However, in recent years there has been a gradual shift towards a more participatory-patient model in Japan. With advances in technology, the possibility to use digital technologies to improve patient interactions is growing and is in line with changing attitudes in the medical profession and society within Japan and elsewhere. The implementation of an online patient engagement platform is being considered by the Myotonic Dystrophy Registry of Japan. The aim of this exploratory study was to understand patients' views and attitudes to using digital tools in patient registries and engagement with medical research in Japan, prior to implementation of the digital platform. METHODS: We conducted an exploratory, cross-sectional, self-completed questionnaire with a sample of myotonic dystrophy (MD) patients attending an Open Day at Osaka University, Japan. Patients were eligible for inclusion if they were 18 years or older, and were diagnosed with MD. RESULTS: A total of 68 patients and family members attended the Open Day and were invited to participate in the survey. Of those, 59 % submitted a completed questionnaire (n = 40). The survey showed that the majority of patients felt that they were not receiving the information they wanted from their clinicians, which included recent medical research findings and opportunities to participate in clinical trials, and 88 % of patients indicated they would be willing to engage with digital technologies to receive relevant medical information. Patients also expressed an interest in having control over when and how they received this information, as well as being informed of how their data is used and shared with other researchers. CONCLUSION: Overall, the findings from this study suggest that there is scope to develop a digital platform to engage with patients so that they can receive information about medical care and research opportunities. While this study group is a small, self-selecting population, who suffer from a particular condition, the results suggest that there are interested populations within Japan that would appreciate enhanced communication and interaction with healthcare teams.

Has the biobank bubble burst? Withstanding the challenges for sustainable biobanking in the digital era.

Biobanks have been heralded as essential tools for translating biomedical research into practice, driving precision medicine to improve pathways for global healthcare treatment and services. Many nations have established specific governance systems to facilitate research and to address the complex ethical, legal and social challenges that they present, but this has not lead to uniformity across the world. Despite significant progress in responding to the ethical, legal and social implications of biobanking, operational, sustainability and funding challenges continue to emerge. No coherent strategy has yet been identified for addressing them. This has brought into question the overall viability and usefulness of biobanks in light of the significant resources required to keep them running. This review sets out the challenges that the biobanking community has had to overcome since their inception in the early 2000s. The first section provides a brief outline of the diversity in biobank and regulatory architecture in seven countries: Australia, Germany, Japan, Singapore, Taiwan, the UK, and the USA. The article then discusses four waves of responses to biobanking challenges. This article had its genesis in a discussion on biobanks during the Centre for Health, Law and Emerging Technologies (HeLEX) conference in Oxford UK, co-sponsored by the Centre for Law and Genetics (University of Tasmania). This article aims to provide a review of the issues associated with biobank practices and governance, with a view to informing the future course of both large-scale and smaller scale biobanks.

Human genetic research, race, ethnicity and the labeling of populations: recommendations based on an interdisciplinary workshop in Japan.

BACKGROUND: A challenge in human genome research is how to describe the populations being studied. The use of improper and/or imprecise terms has the potential to both generate and reinforce prejudices and to diminish the clinical value of the research. The issue of population descriptors has not attracted enough academic attention outside North America and Europe. In January 2012, we held a two-day workshop, the first of its kind in Japan, to engage in interdisciplinary dialogue between scholars in the humanities, social sciences, medical sciences, and genetics to begin an ongoing discussion of the social and ethical issues associated with population descriptors. DISCUSSION: Through the interdisciplinary dialogue, we confirmed that the issue of race, ethnicity and genetic research has not been extensively discussed in certain Asian communities and other regions. We have found, for example, the continued use of the problematic term, "Mongoloid" or continental terms such as "European," "African," and "Asian," as population descriptors in genetic studies. We, therefore, introduce guidelines for reporting human genetic studies aimed at scientists and researchers in these regions. CONCLUSION: We need to anticipate the various potential social and ethical problems entailed in population descriptors. Scientists have a social responsibility to convey their research findings outside of their communities as accurately as possible, and to consider how the public may perceive and respond to the descriptors that appear in research papers and media articles.

The Role of Male Consent in Assisted Reproductive Technology Procedures: an Examination of Japanese Court Cases.

With the development of assisted reproductive technologies, medical, ethical, legal, and social issues have arisen that did not exist when natural conception was the only means of childbirth. In Japan, men tend to believe that assisted reproductive technologies are not directly related to them, with the literature showing that men are often reluctant to be involved in fertility treatment processes. To better understand this situation, this study analyzes the role of male consent during assisted reproductive technology procedures in Japan. First, we examined Japanese court cases that dealt with issues related to male consent during assisted reproductive technology procedures and identified three situations in which problems related to male consent during such procedures may arise. Next, we analyzed the background of such issues and the implications of the lack of consent regarding men's reproductive rights. Finally, we explored the need for legislation on assisted reproductive technologies. The study concludes that discussions on the scope of male partner rights in assisted reproductive technology procedures are key for minimizing unnecessary conflict between partners, thus ensuring both the rights of women who wish to have children and the welfare of their children. Supplementary Information: The online version contains supplementary material available at 10.1007/s41649-023-00274-1.

Access, autonomy, and affordability: ethical and human rights issues surrounding multigene panel testing for cancer in Japan and Switzerland.

Introduction: Advancements in precision medicine and genomics have led to prospects in a wide range of clinical fields, including oncology. In particular, developments in next-generation sequencing multigene panel tests have led to the possibility of tailoring treatment to the specific genomic markers of a patient's cancer. However, findings from current literature suggest that the path to implementation and uptake of genomic medicine is not without uncertainties and challenges. Methods: To better understand the current challenges to the implementation of genomic medicine services, we investigated the current state of patient access to genomic medicine in Japan and Switzerland. In this investigation, we focused on equal access, patient autonomy, and healthcare affordability. Results: Results have shown that although multigene panel testing is in principle covered by health insurance in both countries, barriers exist in terms of where the tests are available, comprehensive information for patients, and the affordability of not only the test itself but the overall process from diagnosis to treatment. Discussion: These results suggest a need to continue examining a more diverse range of clinical landscapes for genomic medicine to reveal more nuanced understandings of barriers to implementation and thus better identify best practices for overcoming them.

Stakeholder Involvement in the Governance of Human Genome Editing in Japan.

Genome editing is a technology that can accurately and efficiently modify the genome of organisms, including the human genome. Although human genome editing (HGE) has many benefits, it also involves technical risks and ethical, legal, and social issues. Thus, the pros and cons of using this technology have been actively debated since 2015. Notably, the research community has taken an interest in the issue and has discussed it internationally. However, for the governance of HGE, the roles of government agencies and the general public are also important for an effective regulatory system. Here, we examine the roles of the research community, government, and public in the governance of HGE through an analysis of discussions in the Japanese Expert Panel on Bioethics. During the discussion of the research ethics review system, the professionalism of the research community and the pros and cons of state oversight have become issues for debate. Furthermore, through an examination of the overall policy-making process, three stakeholders are clearly involved in the governance of emerging medical technologies in the Expert Panel on Bioethics, a discussion forum established by government agencies. The contrast among these roles provides insight into the positive roles of government agencies and the research community and the conditions under which these roles are played. We also note that there are diverse actors in the public, which may have an impact on their participation. Our results may serve as a guide for countries and organizations to establish governance on emerging medical technologies.

Perspectives on artificial intelligence in healthcare from a Patient and Public Involvement Panel in Japan: an exploratory study.

Patients and members of the public are the end users of healthcare, but little is known about their views on the use of artificial intelligence (AI) in healthcare, particularly in the Japanese context. This paper reports on an exploratory two-part workshop conducted with members of a Patient and Public Involvement Panel in Japan, which was designed to identify their expectations and concerns about the use of AI in healthcare broadly. 55 expectations and 52 concerns were elicited from workshop participants, who were then asked to cluster and title these expectations and concerns. Thematic content analysis was used to identify 12 major themes from this data. Participants had notable expectations around improved hospital administration, improved quality of care and patient experience, and positive changes in roles and relationships, and reductions in costs and disparities. These were counterbalanced by concerns about problematic changes to healthcare and a potential loss of autonomy, as well as risks around accountability and data management, and the possible emergence of new disparities. The findings reflect participants' expectations for AI as a possible solution for long-standing issues in healthcare, though their overall balanced view of AI mirrors findings reported in other contexts. Thus, this paper offers initial, novel insights into perspectives on AI in healthcare from the Japanese context. Moreover, the findings are used to argue for the importance of involving patient and public stakeholders in deliberation on AI in healthcare.