Ethical, Legal, and Social Issues (ELSI) in Clinical Genetics Research.

ELSI (Ethical, Legal, and Social Issues) is a widely used acronym in the bioethics literature that encompasses a broad range of research examining the various impacts of science and technology on society. In Canada, GE3LS (Genetics, Ethical, Economic, Environmental, Legal, Social issues) is the term used to describe ELSI studies in the context of genetics and genomics research. It is intentionally more expansive in that GE3LS explicitly brings economic and environmental issues under its purview. ELSI/GE3LS research is increasingly relevant in recent years as there has been a greater emphasis on "translational research" that moves genomic discoveries from the bench to the clinic. The purpose of this chapter is to outline a range of ELSI-related work that might be conducted as part of a large scale genetics or genomics research project, and to provide some practical insights on how a scientific research team might incorporate a strong and effective ELSI program within its broader research mandate. We begin by describing the historical context of ELSI research and the development of GE3LS research in the Canadian context. We then illustrate how some ELSI research might unfold by outlining a variety of GE3LS research questions or content domains and the methodologies that might be employed in studying them. We conclude with some practical suggestions about how to build an effective ELSI/GE3LS team and focus within a broader scientific research program.

Informed Consent for Genetic and Genomic Research.

Genetic research often utilizes or generates information that is potentially sensitive to individuals, families, or communities. For these reasons, genetic research may warrant additional scrutiny from investigators and governmental regulators, compared to other types of biomedical research. The informed consent process should address the range of social and psychological issues that may arise in genetic research. This article addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. © 2020 Wiley Periodicals LLC.

Challenges of Genetic Data Sharing in African Studies.

Data sharing is a valuable aspect of science and required by most funding bodies and journals. However, the national regulatory guidelines of many African nations do not explicitly allow for broad genetic data sharing. Given these restrictions, there is a need to reconsider these policies and propose creative solutions.

Genomic research and privacy: A response to Staunton et al.

The Protection of Personal Information Act No. 4 of 2013 (POPIA) promises a new dispensation of privacy protection for research participants in South Africa. In a recent article, Staunton et al. proposed that a purposive interpretation of POPIA would allow for the retention of the status quo of broad consent in the context of genomic research. In this response article, we analyse the argument presented by Staunton et al., and conclude that it fails to convince: firstly, because Staunton et al. do not present empirical data for their factual assumption that moving up the consent benchmark is likely to stymie research; secondly, because genomic research does not have a monopoly on the public interest, but shares it with the privacy rights of research participants; and thirdly, because POPIA was designed to promote the protection of privacy, not simply to preserve the status quo as found in existing policy instruments. In contrast to the position advocated by Staunton et al., we suggest that a purposive interpretation of POPIA is aligned with the plain meaning of the statute - namely that specific (not broad) consent is a prerequisite for research on genomic information.This article, which comments on an article by Staunton et al. (Staunton C, Adams R, Botes M, et al. Safeguarding the future of genomic research in South Africa: Broad consent and the Protection of Personal Information Act No. 4 of 2013. S Afr Med J 2019;109(7):468-470. https://doi.org/10.7196/SAMJ.2019.v109i7.14148), is followed by a letter by Thaldar and Townsend (Privacy rights of human research participants in South Africa must be taken seriously. S Afr Med J 2020;110(3):175-176. https://doi.org/10.7196/SAMJ.2020.v110i3.14450); and a response to the article and letter by Staunton et al. (S Afr Med J 2020;110(3):175-176. https://doi.org/10.7196/SAMJ.2020.v110i3.14450).

Implementation of Nagoya Protocol on access and benefit-sharing in Peru: Implications for researchers.

ETHNOPHARMACOLOGICAL RELEVANCE: The Peruvian Amazon holds more than 1000 plant species with commercial potential and the national sales of natural products derived from medicinal and aromatic plants have exceeded $ 400 million per year. Research and development activities carried out on the genetic and biochemical composition of Peruvian flora have to abide by national and international regulations, such as the Nagoya Protocol (NP). AIM OF THE STUDY: The aim of this paper is to describe the implications of the current implementation of the NP in Peru for performing research on national genetic resources. MATERIALS AND METHODS: A review of the current legal framework and status of the NP in Peru was performed accompanied by first-hand experience undertaken by submitting a request for access to genetic resources related to wild continental species. RESULTS: So far, Peru has issued 16 Internationally Recognized Certificates of Compliance (IRCCs) through 2 of the identified National Authorities. Some of the difficulties and challenges observed have to do with the degree of effective implementation of the Access and Benefit-Sharing (ABS) system, the fact that the application process is not sufficiently clear, and the wide gap between this formal system and what occurs informally outside of it. In response to this, training and implementation projects have been launched and a new law on the access to genetic resources has been proposed. CONCLUSIONS: The difficulties observed still represent an obstacle to scientific research and the development of new commercial products based on Peruvian traditional knowledge and genetic resources. Although improvements have been made to the ABS framework, there remain major challenges to encouraging and ascertaining the equitable and sustainable use of Peru's biodiversity.

Do patients and research subjects have a right to receive their genomic raw data? An ethical and legal analysis.

BACKGROUND: As Next Generation Sequencing technologies are increasingly implemented in biomedical research and (translational) care, the number of study participants and patients who ask for release of their genomic raw data is set to increase. This raises the question whether research participants and patients have a legal and moral right to receive their genomic raw data and, if so, how this right should be implemented into practice. METHODS: In a first step we clarify some central concepts such as "raw data"; in a second step we sketch the international legal framework. The third step provides an extensive ethical analysis which comprehends two parts: an evaluation of whether there is a prima facie moral right to receive one's raw data, and a contextualization and discussion of the right in light of potentially conflicting interests and rights of the data subject herself and third parties; in a last fourth step we emphasize the main practical consequences of the ethical analyses and propose recommendations for the release of raw data. RESULTS: In several legislations like the new European General Data Protection Regulation, patients do in principle have the right to receive their raw data. However, the procedural implementation of this right and whether it involves genetic counselling is at the discretion of the Member States. Even more questions remain with respect to the research context. The ethical analysis suggests that patients and research subjects have a moral right to receive their genomic raw data and addresses aspects which are also of relevance for the legal discussion such as the costs of release of raw data and its impact on academic freedom. CONCLUSION: Taking into account the specific nature and implications of genomic raw data and the contexts of research and health care, several concerns and potentially conflicting interests of the data subjects themselves and involved researchers, physicians, biomedical institutions and relatives arise. Instead of using them to argue in favor of restrictions of the data subjects' legal and moral right to genomic raw data, the concerns should be addressed through provision of information and other measures. To this end, we propose relevant recommendations.

Legal Challenges in Genetics, Including Duty to Warn and Genetic Discrimination.

This review will explore two legal issues in genetic counseling: genetic discrimination and the duty to warn. It emphasizes the complexity and variability of federal and state genetic nondiscrimination protections in the United States and how the many gaps in such protections may affect people pursuing genetic testing. The limited law addressing legal obligations genetic counselors owe at-risk relatives likely does not require counselors to warn relatives directly about genetic risks. Whether it permits them to make such disclosures, however, is more uncertain and may depend on the jurisdiction.

Edición genómica y libertad de investigación: ¿nuevos retos para viejos derechos? / Genome editing and scientific freedom: new challenges for old rights?

El sistema CRISPR-Cas ha permitido editar el genoma de células y organismos vivos de forma sencilla y precisa. Pese a su extendido uso en diversas áreas de investigación en Biología, incluida la Biomedicina, existen problemas de seguridad que han de ser analizados antes de que el llamado 'bisturí molecular' llegue a la práctica clínica. Sin embargo, en noviembre de 2018, un científico chino aseguró haber creado las dos primeras bebés editadas genéticamente para conferirles resistencia al VIH. El experimento abre el debate sobre la libertad de investigación, un derecho fundamental que no solo ha permitido importantes avances en Genética, sino que también podría afectar otros derechos y libertades. El presente artículo aborda los desafíos en la relación entre la edición genómica y la libertad de investigación

The CRISPR-Cas system has enabled scientists to easily and precisely edit the genome in cells and living organisms. Despite its widespread use in many biological research areas, including Biomedicine, there are still important safety issues that need to be addressed before translating the so-called 'molecular scalpel' to clinical practice. However, in November 2018, a Chinese scientist claimed to had created the first genetically edited babies to make them more resistant to HIV. The experiment opens the debate about scientific freedom, a fundamental right that not only has allowed important advances in Genetics, but could also affect other rights and liberties. The present article discusses the challenges ahead the relationship between genome editing and scientific freedom

La tutela jurídico-penal de los datos genéticos con fines médicos / The legal and criminal protection of genetic data for medical purposes

El artículo realiza una valoración en torno a la evolución de la medicina del futuro y su incidencia en la protección de los derechos fundamentales. El autor centra su discurso en dos enfoques que, en la actualidad, parecen dominar el campo de la medicina: la medicina genómica y la medicina personalizada de precisión, entendiendo que existen diferencias entre medicina genómica y medicina personalizada de precisión que no permiten identificarlas. Una amplia exposición es dedicada al tema que el autor considera más relevante en la actualidad, esto es, el de la medicina personalizada de precisión, íntimamente ligada a los big data y a la inteligencia artificial

This paper deals with the evolution of the medicine of the future and its impact on the protection of fundamental rights. The author focuses the discourse on two approaches that currently seem to dominate the field of medicine: genomic medicine and personalized precision medicine, understanding that there are differences between genomic medicine and personalized precision medicine that do not allow them to be identified. An extensive exposition is dedicated to the subject that the author considers most relevant today, that is, precision personalized medicine, intimately linked to big data and artificial intelligence

Return of individual genomic research results: are laws and policies keeping step?

Efforts are underway to harmonise the return of individual results and incidental findings from whole genome sequencing (WGS) across research contexts and countries. We reviewed international, regional and national laws and policies applying to return across 20 countries to identify areas of convergence and divergence. Discrepancies between laws and policies are most problematic where they cannot be reconciled through harmonisation of project-level governance. Rules for the return of results apply at different levels in different jurisdictions (e.g., human subjects research, biobanks, clinical trials, genomic sequencing, and genetic/personal data), complicating comparison. A particular concern for harmonisation are the (often contradictory) rules about when results must, should, may, or must not be returned. Adding confusion are different thresholds for utility (medical, familial, reproductive, and/or personal). The importance of respecting individual choices to know or not know is widely recognised, though some norms emphasise respect for personal preferences. Another troubling observation is that requirements for data quality, variant assessment, and the effective communication of results are evolving in uneven ways. There is a growing gap between researchers with the expertise, infrastructure, and resources to meet these requirements and those without, threatening international collaboration. Best practices for the return of individual genomic results are sorely needed to inform not only the ethical return of results, but also future legislative and policy efforts.

Ethical and Legal Considerations for the Inclusion of Underserved and Underrepresented Immigrant Populations in Precision Health and Genomic Research in the United States.

There has been growing recognition of the importance of diversity and inclusion of underrepresented minority populations, including immigrants, in genomic research and precision medicine. Achieving diversity has been difficult and has led some scholars to question whether the law is a help or a threat to the inclusion of underserved and underrepresented immigrant populations. In this commentary, I provide an overview of some of the many relevant legal issues affecting the inclusion of immigrants in genomic research and precision health initiatives, such as the All of UsSM Research Program. Development of research recruitment, retention, and data collection plans without also considering the legal and sociopolitical context within which such efforts are to be carried out is risky. Advancing health policy with a goal of eliminating health disparities (or, at a minimum, ensuring that health disparities are not exacerbated by genomic or precision health technologies) requires us to acknowledge the negative effects that immigration policy and criminal justice policy have on the involvement of immigrants in such research and on their health directly. I conclude that it is not a question of whether the law is a help or a threat but, rather, whether we collectively will prioritize authentic diversity and inclusion policies and also insist on compliance with the laws intended to ensure the human right of every individual - regardless of immigration status or national origin - to share in the advancement of science.

Genetic research and consent: On the crossroads of human and data research.

This paper explores the legal and ethical concept of human subject research in order to determine whether genetic research with already available biosamples and data falls within this concept. Although the ethical concept seems to have evolved to recognize research based on data as human research, from a supranational legal perspective this form of research is not considered human subject research. Thus human subject research regulations do not apply and therefore do not invoke the requirement of obtaining consent prior to using an individual's biosample or genetic data in research. Furthermore, it remains ambiguous in both the legal and ethical realm whether the use of biosamples or genetic data without additional links to the individual would invoke the same safeguards as research involving additional or specific identifiers. Seeing that research based on already available biosamples and genetic data is not governed by rules concerning human subject research, the second part of the paper analyses whether any consent requirements apply for the further use of already available bio-samples or genetic data in research. Whereas further use of biosamples is subject to considerably lax consent requirements under Article 22 of the Oviedo Convention, under the General Data Protection Regulation further use of genetic data might not be subject to a prior consent requirement at all, unless it is stipulated in national laws. When it comes to clinical trials, however, sponsors will have the possibility under Article 28(2) of Regulation 536/2014 to obtain open consent for further use of data in any kind of future research.

Returning Results to Family Members: Professional Duties in Genomics Research in the United States.

 This article critically appraises the ethical and legal duties to disclose findings to the family members of research participants. These family members stand to benefit in important ways from discoveries that can inform their own health and reproductive risks. However, careful appreciation of how medical research differs from clinical practice and of the uncertainties at stake in genomic research complicates any warning to relatives. Research laboratories should generally be immune from liability for failing to diagnose or disclose a genetic disorder in time to prevent adverse outcomes for a participant's family members or to return properly interpreted test results for even direct findings under investigation, let alone incidental ones. The only exception is where warning relatives of medical risks is very likely to prevent imminent harm and would not override known participant wishes. Genomic autopsy studies for sudden death satisfy these conditions of life-saving potential for relatives without disrespect to subjects. These are among the rare instances in which we conclude that offering results to family members is not just permissible but obligatory, not just as a moral matter but as a legal one.

Should NASA Collect Astronauts' Genetic Information for Occupational Surveillance and Research?

Humans exploring beyond low-Earth orbit face environmental challenges coupled with isolation, remote operations, and extreme resource limitations in which personalized medicine, enabled by genetic research, might be necessary for mission success. With little opportunity to test personalized countermeasures broadly, the National Aeronautics and Space Administration (NASA) will likely need to rely instead on collection of significant amounts of genomic and environmental exposure data from individuals. This need appears at first to be in conflict with the statutes and regulations governing the collection and use of genetic data. In fact, under certain conditions, the Genetic Information Nondiscrimination Act (GINA) of 2008 allows for the use of genetic information in both occupational surveillance and research and in the development of countermeasures such as personalized pharmaceuticals.

Germany: a fair balance between scientific freedom and data subjects' rights?

With the German Bundestag's adoption of the Data Protection Adaptation and Implementation Act EU (DSAnpUG-EU) on 30 June 2017, the adaptation of German law to the General Data Protection Regulation (GDPR) has begun (Gesetz zur Anpassung des Datenschutzrechts an die Verordnung (EU) 2016/679 und zur Umsetzung der Richtlinie (EU) 2016/680 (Datenschutz-Anpassungs- und -Umsetzungsgesetz-DSAnpUG-EU) v. 30. Juni 2017, BGBl. 2017 I p. 2097 et seq.). Despite being directly binding on all EU member states, the GDPR does not render national data protection provision obsolete-they are covered by the GDPR's opening clauses which include regulatory mandates and room for derogation. This creates considerable need for national legislative adaptation. Art. 1 DSAnpUG-EU contains the necessary amendments to the Federal Data Protection Law (BDSG(neu)), thus creating the second major building block of future German data protection alongside the GDPR itself. Nevertheless, there are still numerous sector-specific regulations in other federal laws and the data protection laws of the 16 states also need amendments. Adjustment in Germany is well on its way, but implementation in general is still ongoing, with further consequences for data processing and sharing.

Australia: regulating genomic data sharing to promote public trust.

The regulation of genomic data sharing in Australia is a confusing mix of common law, legislation, ethical guidelines, and codes of practice. Beyond privacy laws, which only apply to genomic data that meets the definition of personal information, the key regulatory lever is the National Health and Medical Research Council (NHMRC) National Statement for Ethical Conduct in Human Research ("National Statement") (2007). Compliance with the National Statement is a requirement for institutions to apply to the NHMRC for funding, and includes-among other things-requirements for review of most genomic research by Human Research Ethics Committees. The sections of the National Statement specifying requirements for research with human genomic data are currently under review, including proposed new requirements addressing the return of genetic research findings and oversight of transfer agreements. Ensuring the willingness of Australians to donate their genomic information and participate in medical research will require clarification and harmonisation of the applicable regulatory framework, along with reforms to ensure that these regulations reflect the conditions necessary to promote ongoing public trust in researchers and institutions.

Conclusion: harmonisation in genomic and health data sharing for research: an impossible dream?

There are clear benefits from genomics and health data sharing in research and in therapy for individuals across societies. At the same time, citizens have different expectations and fears about that data sharing. International legislation in relation with research ethics and practice and, particularly, data protection create a particular environment that, as is seen in the articles in part two of this special issue, are crying out for harmonisation both at a procedural but at fundamental conceptual levels. The law of data sharing is pulling in different directions. This paper poses the question, 'harmonisation, an impossible dream?' and the answer is a qualified 'no'. The paper reflects on what can be seen in the papers in part two of the special issue. It then identifies three major areas of conceptual uncertainty in the new EU General Data Protection Regulation (not because it has superiority over other jurisdictions, but because it is a recent revision of data protection law that leaves universal conceptual questions unclear). Thereafter, the potential for Artificial Intelligence to meet some of the shortcomings is discussed. The paper ends with a consideration of the conditions under which data sharing harmonisation might be achieved: an understanding of a human rights approach and citizen sensitivities in considering the 'public interest'; social liberalism as a basis of solidarity; and the profession of 'researcher'.

United Kingdom: transfers of genomic data to third countries.

In the United Kingdom (UK), transfer of genomic data to third countries is regulated by data protection legislation. This is a composite of domestic and European Union (EU) law, with EU law to be adopted as domestic law when Brexit takes place. In this paper we consider the content of data protection legislation and the likely impact of Brexit on transfers of genomic data from the UK to other countries. We examine the advice by regulators not to rely upon consent as a lawful basis for processing under data protection law, at least not when personal data are used for research purposes, and consider some of the other ways in which the research context can qualify an individual's ability to exercise control over processing operations. We explain how the process of pseudonymization is to be understood in the context of transfer of genomic data to third parties, as well as how adequacy of data protection in a third country is to be determined in general terms. We conclude with reflections on the future direction of UK data protection law post Brexit with the reclassification of the UK itself as a third country.