The Myriad Decision at 10.

A decade ago, the US Supreme Court decided Association for Molecular Pathology v. Myriad Genetics, Inc., concluding that isolated genes were not patentable subject matter. Beyond being a mere patent dispute, the case was a political and cultural phenomenon, viewed as a harbinger for the health of the biotechnology industry. With a decade of perspective, though, Myriad's impact seems much narrower. The law surrounding patentable subject matter-while greatly transformed-only centered on Myriad in small part. The case had only a modest impact on patenting practices both in and outside the United States. And persistent efforts to legislatively overturn the decision have not borne fruit. The significance of Myriad thus remains, even a decade later, hidden by larger developments in science and law that have occurred since the case was decided. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 25 is August 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Science fiction and ELSI: three thoughts.

Science fiction can be useful to those who analyze ethical, legal, and social issues (ELSI) in genetics and the biosciences more broadly. It can provide examples of possible technological changes, which are occasionally valuable as predictions of the future but more often helpful as indicators of the likely social consequences of such technologies. This "what-if" approach to science fiction can also provide a good pathway to exploring such issues. Science fiction can also allow a more distant, less realistic, and non-culture-specific context for exploring deep questions about humanity, ethics, and other major issues. At the same time, science fiction also has some negative effects on such analysis or its reception as a result of the need for fiction to hold its audience by providing drama through conflict. This necessity for successful fiction often leads to technological or cultural changes being portrayed as catastrophic and dystopian, much more often than beneficial or utopian. This imbalance can predispose public opinion against innovations unfairly, in part by providing "examples" from fiction of similar innovations, leading to bad outcomes. ELSI researchers should keep this fiction-induced bias in mind in their work.

Ethical, legal and social aspects of human cerebral organoids and their governance in Germany, the United Kingdom and the United States.

Human cerebral organoids (HCOs) are model systems that enable researchers to investigate the human brain in ways that had previously been impossible. The emergence of HCOs was accompanied by both expert and layperson discussions concerning the possibility of these novel entities developing sentience or consciousness. Such concerns are reflected in deliberations about how to handle and regulate their use. This perspective article resulted from an international and interdisciplinary research retreat "Ethical, Legal and Social Aspects of Human Cerebral Organoids and their Governance in Germany, the United Kingdom and the United States", which took place in Tübingen, Germany, in August 2022. The retreat focused on whether HCO research requires new ethical and regulatory approaches. It addressed epistemic issues around the detection and theorisation of consciousness, ethical concerns around moral status and research conduct, difficulties for legislation and guidelines managing these entities, and public engagement.

Ethically cleared to launch?

Rules are needed for human research in commercial spaceflight.

Public health versus personalized medicineTyranny of the Gene James Tabery Knopf, 2023. 336 pp.

Environmental health research is being undermined by genomic medicine, argues a philosopher.

Clarifying the Ethics and Oversight of Chimeric Research.

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human-nonhuman chimeric research. Led by bioethics researchers working closely with an interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human-nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics' previous focus on human-centered questions about the ethics of "humanization" and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less-siloed governance and oversight and more-comprehensive public communication.

The death of Roe and the future of ex vivo embryos.

This article examines the possible effects of the end of a federal constitutional right to abortion on clinical practice and research involving ex vivo human embryos. It first analyzes the likely outcomes of Dobbs v. Mississippi, concluding the Supreme Court will either overrule the federal constitutional abortion right or restrict it in a way that leads to its rapid disappearance. Next, the article discusses a possible increase in use of preimplantation genetic testing as one result. It then forecasts the likely ramifications of such a court decision on state legislation affecting ex vivo human embryos in two ways. It examines the possibility that victory over Roe will inspire embryo support groups to push for limitations on in vitro fertilization, perhaps on its destruction of embryos and more likely on permissible grounds for prospective parents to use in choosing embryos for transfer. It ends by discussing the prospects of new laws in some states banning or limiting research with human embryos.

Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work.

Advancing models of neural development with biomaterials.

Human pluripotent stem cells have emerged as a promising in vitro model system for studying the brain. Two-dimensional and three-dimensional cell culture paradigms have provided valuable insights into the pathogenesis of neuropsychiatric disorders, but they remain limited in their capacity to model certain features of human neural development. Specifically, current models do not efficiently incorporate extracellular matrix-derived biochemical and biophysical cues, facilitate multicellular spatio-temporal patterning, or achieve advanced functional maturation. Engineered biomaterials have the capacity to create increasingly biomimetic neural microenvironments, yet further refinement is needed before these approaches are widely implemented. This Review therefore highlights how continued progression and increased integration of engineered biomaterials may be well poised to address intractable challenges in recapitulating human neural development.

Ethical Development of Digital Phenotyping Tools for Mental Health Applications: Delphi Study.

BACKGROUND: Digital phenotyping (also known as personal sensing, intelligent sensing, or body computing) involves the collection of biometric and personal data in situ from digital devices, such as smartphones, wearables, or social media, to measure behavior or other health indicators. The collected data are analyzed to generate moment-by-moment quantification of a person's mental state and potentially predict future mental states. Digital phenotyping projects incorporate data from multiple sources, such as electronic health records, biometric scans, or genetic testing. As digital phenotyping tools can be used to study and predict behavior, they are of increasing interest for a range of consumer, government, and health care applications. In clinical care, digital phenotyping is expected to improve mental health diagnoses and treatment. At the same time, mental health applications of digital phenotyping present significant areas of ethical concern, particularly in terms of privacy and data protection, consent, bias, and accountability. OBJECTIVE: This study aims to develop consensus statements regarding key areas of ethical guidance for mental health applications of digital phenotyping in the United States. METHODS: We used a modified Delphi technique to identify the emerging ethical challenges posed by digital phenotyping for mental health applications and to formulate guidance for addressing these challenges. Experts in digital phenotyping, data science, mental health, law, and ethics participated as panelists in the study. The panel arrived at consensus recommendations through an iterative process involving interviews and surveys. The panelists focused primarily on clinical applications for digital phenotyping for mental health but also included recommendations regarding transparency and data protection to address potential areas of misuse of digital phenotyping data outside of the health care domain. RESULTS: The findings of this study showed strong agreement related to these ethical issues in the development of mental health applications of digital phenotyping: privacy, transparency, consent, accountability, and fairness. Consensus regarding the recommendation statements was strongest when the guidance was stated broadly enough to accommodate a range of potential applications. The privacy and data protection issues that the Delphi participants found particularly critical to address related to the perceived inadequacies of current regulations and frameworks for protecting sensitive personal information and the potential for sale and analysis of personal data outside of health systems. CONCLUSIONS: The Delphi study found agreement on a number of ethical issues to prioritize in the development of digital phenotyping for mental health applications. The Delphi consensus statements identified general recommendations and principles regarding the ethical application of digital phenotyping to mental health. As digital phenotyping for mental health is implemented in clinical care, there remains a need for empirical research and consultation with relevant stakeholders to further understand and address relevant ethical issues.

Advancing the ethical dialogue about monkey/human chimeric embryos.

In this issue of Cell, Tan et al. report the first injection of human stem cells into in vitro non-human primate blastocysts with significant survival of the human cells, raising new scientific possibilities but also important ethical issues.

Human Brain Surrogates Research: The Onrushing Ethical Dilemma.

Human brain research is moving into a dilemma. The best way to understand how the human brain works is to study living human brains in living human beings, but ethical and legal standards make it difficult to do powerful research with actual human beings. So neuroscientists have developed four types of surrogates for living human brains in human bodies: genetically edited non-human animals, human/non-human brain chimeras, human neural organoids, and living ex vivo human brain tissues. These new and rapidly improving models offer the hope of understanding human brain function better. If we make our models "too good," they may themselves deserve some of the kinds of ethical and legal respect that have limited brain research in human beings. This article is an initial effort to outline that dilemma.

Reactions to the National Academies/Royal Society Report on Heritable Human Genome Editing.

In September 2020, a detailed report on Heritable Human Genome Editing was published. The report offers a translational pathway for the limited approval of germline editing under limited circumstances and assuming various criteria have been met. In this perspective, some three dozen experts from the fields of genome editing, medicine, bioethics, law, and related fields offer their candid reactions to the National Academies/Royal Society report, highlighting areas of support, omissions, disagreements, and priorities moving forward.

Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research.

The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.

COVID-19 immunity certificates: science, ethics, policy, and law.

There is much discussion of adopting COVID-19 immunity certificates to allow those proven to have antibodies to the SARS-CoV-2 virus that causes COVID-19 to resume normal life and help restart the economy. This article points out issues that must be considered before adopting any such program. These issues fall into six categories: the uncertain science of COVID-19 immunity; the questionable quality of COVID-19 antibody tests; practical problems with issuing such certificates; deciding how the certificates might be used; ethical and social issues they would raise, especially fairness and self-infection; and potential legal barriers. It does not ultimately take a position on whether some narrow COVID-19 immunity plans should be adopted, concluding that the answer depends on too many currently unknown conditions. But its seventh part makes recommendations to decision-makers who might consider implementing such programs.