Dynamic models of human development and concepts of the individual.

Stem cells can be coaxed to self-organize into dynamic models of human development and early embryo formation. Despite their scientific promise, might widespread use of these technologies alter people's beliefs about what it means to be a human individual? Attention to some important philosophical distinctions may help navigate our thinking.

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.

Ethical considerations for human-animal neurological chimera research: mouse models and beyond.

Research that uses stem cell-based chimeras promises to advance our understanding of human developmental biology, as well as new medical interventions, such as generating transplantable human organs in livestock. However, along with these exciting research possibilities come moral concerns about the moral humanization of animals, especially when it comes to the potential effects of human cells in the brains of experimental animals. Recent work involving neurologically chimeric mice may suggest that such worries are reasonable. However, this overlooks the crucial social and neurological conditions for enabling the development of conscious self-awareness, the absence of which leaves us only with animal welfare to monitor and consider.

Acceptance of genetic editing and of whole genome sequencing of human embryos by patients with infertility before and after the onset of the COVID-19 pandemic.

RESEARCH QUESTION: Has acceptance of heritable genome editing (HGE) and whole genome sequencing for preimplantation genetic testing (PGT-WGS) of human embryos changed after the onset of COVID-19 among infertility patients? DESIGN: A written survey conducted between April and June 2018 and July and December 2021 among patients at a university-affiliated infertility practice. The questionnaire ascertained the acceptance of HGE for specific therapeutic or genetic 'enhancement' indications and of PGT-WGS to prevent adult disease. RESULTS: In 2021 and 2018, 172 patients and 469 patients (response rates: 90% and 91%, respectively) completed the questionnaire. In 2021, significantly more participants reported a positive attitude towards HGE, for therapeutic and enhancement indications. In 2021 compared with 2018, respondents were more likely to use HGE to have healthy children with their own gametes (85% versus 77%), to reduce disease risk for adult-onset polygenic disorders (78% versus 67%), to increase life expectancy (55% versus 40%), intelligence (34% versus 26%) and creativity (33% versus 24%). Fifteen per cent of the 2021 group reported a more positive attitude towards HGE because of COVID-19 and less than 1% a more negative attitude. In contrast, support for PGT-WGS was similar in 2021 and 2018. CONCLUSIONS: A significantly increased acceptance of HGE was observed, but not of PGT-WGS, after the onset of COVID-19. Although the pandemic may have contributed to this change, the exact reasons remain unknown and warrant further investigation. Whether increased acceptability of HGE may indicate an increase in acceptability of emerging biomedical technologies in general needs further investigation.

Rethinking organoid technology through bioengineering.

In recent years considerable progress has been made in the development of faithful procedures for the differentiation of human pluripotent stem cells (hPSCs). An important step in this direction has also been the derivation of organoids. This technology generally relies on traditional three-dimensional culture techniques that exploit cell-autonomous self-organization responses of hPSCs with minimal control over the external inputs supplied to the system. The convergence of stem cell biology and bioengineering offers the possibility to provide these stimuli in a controlled fashion, resulting in the development of naturally inspired approaches to overcome major limitations of this nascent technology. Based on the current developments, we emphasize the achievements and ongoing challenges of bringing together hPSC organoid differentiation, bioengineering and ethics. This Review underlines the need for providing engineering solutions to gain control of self-organization and functionality of hPSC-derived organoids. We expect that this knowledge will guide the community to generate higher-grade hPSC-derived organoids for further applications in developmental biology, drug screening, disease modelling and personalized medicine.

Ethical issues in human organoid and gastruloid research.

Research involving human organoids and gastruloids involves ethical issues associated with their derivation as well as their current and future uses. These include unique issues related to the extent of maturation that can be achieved in vitro or through chimeric research, as well as fundamental ethical considerations such as those concerning the provenance of human biomaterials and the use of gene-editing technologies. Many of these issues are not specifically addressed by existing ethics oversight mechanisms, but these mechanisms might be easily extended to help ensure that human organoid and related research moves forward in an ethically appropriate manner.

What's Wrong with Human/Nonhuman Chimera Research?

The National Institutes of Health (NIH) is poised to lift its funding moratorium on research involving chimeric human/nonhuman embryos, pending further consideration by an NIH steering committee. The kinds of ethical concerns that seem to underlie this research and chimera research more generally can be adequately addressed.

From naïve pluripotency to chimeras: a new ethical challenge?

In recent years, there has been much interest in the prospect of generating and using human stem cells that exhibit a state of naïve pluripotency. Such a pluripotent state might be functionally confirmed by assessing the chimeric contribution of these cells to non-human blastocysts. Furthermore, the generation of naïve human pluripotent stem cells in vitro could lead to the creation of chimeric animal models that can facilitate the study of human development and disease. However, these lines of research raise thorny ethical concerns about the moral status of such chimeric animals. Here, I call attention to these ethical barbs and suggest a way in which to proceed cautiously.

New monkey embryo models-it's getting complicated.

Li et al.1 report on the generation of cynomolgus monkey models of blastocyst-stage embryos (called "blastoids") using naive cynomolgus embryonic stem cells. These blastoids recapitulate gastrulation in vitro and induce early pregnancy responses when transferred into cynomolgus monkey surrogates, prompting consideration of the policy implications for human blastoid research.

A Multistakeholder Perspective on Advancing Individualized Therapeutics.

Precision medicine has evolved from the application of pharmacogenetic biomarkers to the prospective development of targeted therapies in patients with specific molecular/genetic subtypes of disease to truly "N-of-1" medicines targeted to very small numbers of patients - in some cases, a single identified patient. This latter iteration of precision medicine presents unprecedented opportunities for patients with severe, life-threatening, or life-limiting diseases. At the same time, these modalities present complex scientific, clinical, and regulatory challenges. To realize the promise of individualized medicines, a multistakeholder approach to streamlining medical diagnoses, advancing the technologies that enable development of these therapeutic modalities, and re-envisioning collaborative environments for access and evidence generation is of critical importance. Herein, we highlight some of these challenges and opportunities.

Neuroethical implications of focused ultrasound for neuropsychiatric illness.

BACKGROUND: MR-guided focused ultrasound is a promising intervention for treatment-resistant mental illness, and merits contextualized ethical exploration in relation to more extensive ethical literature regarding other psychosurgical and neuromodulation treatment options for this patient population. To our knowledge, this topic has not yet been explored in the published literature. OBJECTIVE: The purpose of this paper is to review and discuss in detail the neuroethical implications of MR-guided focused ultrasound for neuropsychiatric illness as an emerging treatment modality. METHODS: Due to the lack of published literature on the topic, the approach involved a detailed survey and review of technical and medical literature relevant to focused ultrasound and established ethical issues related to alternative treatment options for patients with treatment-resistant, severe and persistent mental illness. The manuscript is structured according to thematic and topical findings. RESULTS: This technology has potential benefits for patients suffering with severe mental illness, compared with established alternatives. The balance of technical, neuroscientific and clinical considerations should inform ethical deliberations. The nascent literature base, nuances in legal classification and permissibility depending upon jurisdiction, influences of past ethical issues associated with alternative treatments, tone and framing in media articles, and complexity of clinical trials all influence ethical assessment and evaluations of multiple stakeholders. Recommendations for future research are provided based on these factors. CONCLUSION: Salient ethical inquiry should be further explored by researchers, clinicians, and ethicists in a nuanced manner methodologically, one which is informed by past and present ethical issues related to alternative treatment options, broader psychiatric treatment frameworks, pragmatic implementation challenges, intercultural considerations, and patients' ethical concerns.