Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion.

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant.

The Need for Early Engagement with Interested Groups on Advanced Biopreservation.

Research on advanced biopreservation - technologies that include, for example, partial freezing, supercooling, and vitrification with nanoparticle infusion and laser rewarming - is proceeding at a rapid pace, potentially affecting many areas of medicine and the life sciences, food, agriculture, and environmental conservation. Given the breadth and depth of its medical, scientific, and corresponding social impacts, advanced biopreservation is poised to emerge as a disruptive technology with real benefits, but also ethical challenges and risks. Early engagement with potentially affected groups can help navigate possible societal barriers to adoption of this new technology and help ensure that emerging capabilities align with the needs, desires, and expectations of a broad range of interested parties.

Building Governance & Coordination Across Applications.

Advanced biopreservation technologies using subzero approaches such as supercooling, partial freezing, and vitrification with reanimating techniques including nanoparticle infusion and laser rewarming are rapidly emerging as technologies with potential to radically disrupt biomedicine, research, aquaculture, and conservation. These technologies could pause biological time and facilitate large-scale banking of biomedical products including organs, tissues, and cell therapies.

Governing new technologies that stop biological time: Preparing for prolonged biopreservation of human organs in transplantation.

Time limits on organ viability from retrieval to implantation shape the US system for human organ transplantation. Preclinical research has demonstrated that emerging biopreservation technologies can prolong organ viability, perhaps indefinitely. These technologies could transform transplantation into a scheduled procedure without geographic or time constraints, permitting organ assessment and potential preconditioning of the recipients.

Governing with public engagement: an anticipatory approach to human genome editing.

In response to calls for public engagement on human genome editing (HGE), which intensified after the 2018 He Jiankui scandal that resulted in the implantation of genetically modified embryos, we detail an anticipatory approach to the governance of HGE. By soliciting multidisciplinary experts' input on the drivers and uncertainties of HGE development, we developed a set of plausible future scenarios to ascertain publics values-specifically, their hopes and concerns regarding the novel technology and its applications. In turn, we gathered a subset of multidisciplinary experts to propose governance recommendations for HGE that incorporate identified publics' values.

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.

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.

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.

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.

New monkey embryo models-it's getting complicated.

Li et al. 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.

Stem cell ethics and policy: What's old is new again.

Stem cells are increasingly being used to model human development and disease in the form of self-organizing embryo models, brain organoids, and neurological chimeras. These new research directions are resurrecting old embryo debates around moral status and personhood. Hyun considers how these old questions are tackled in these new contexts.

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.

Moral Status and the Oversight of Research Involving Chimeric Animals.

The use of nonhuman animals in research has long been a source of bioethical and scientific debate. We consider the oversight and use of nonhuman animals in chimeric research. We conducted interviews with twelve members of embryonic stem cell research oversight committees, nine members of institutional animal care and use committees, and fourteen scientists involved in human-nonhuman-animal chimeric research in different areas of the United States.

The need for a standard for informed consent for collection of human fetal material.

The ISSCR has developed the Informed Consent Standards for Human Fetal Tissue Donation and Research to promote uniformity and transparency in tissue donation and collection. This standard is designed to assist those working with and overseeing the regulation of such tissue and reassure the wider community and public.

Rescuing human fetal tissue research in the United States: A call for additional regulatory reform.

Research using human fetal tissue has saved millions of lives through vaccines and other advances, but was markedly restricted by federal regulations in 2019. Although the restrictions were partially reversed in 2021, additional regulatory changes are needed to prevent further damage to essential research programs while preserving protection for human subjects.

ISSCR guidelines for the transfer of human pluripotent stem cells and their direct derivatives into animal hosts.

The newly revised 2021 ISSCR Guidelines for Stem Cell Research and Clinical Translation includes scientific and ethical guidance for the transfer of human pluripotent stem cells and their direct derivatives into animal models. In this white paper, the ISSCR subcommittee that drafted these guidelines for research involving the use of nonhuman embryos and postnatal animals explains and summarizes their recommendations.

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.

Ethical issues related to brain organoid research.

This review provides a snapshot of the current ethical issues related to research with human brain organoids. The issues fall into the following main themes: research oversight; human biomaterials procurement and donor consent; translational delivery; animal research; and organoid consciousness and moral status. Each of these areas poses challenges for researchers, bioethicists, regulators, research institutions, and tissue banks.