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. (shrink)

Ranging from miniaturized biological robots to organoids, multi-cellular engineered living systems (M-CELS) pose complex ethical and societal challenges. Some of these challenges, such as how to best distribute risks and benefits, are likely to arise in the development of any new technology. Other challenges arise specifically because of the particular characteristics of M-CELS. For example, as an engineered living system becomes increasingly complex, it may provoke societal debate about its moral considerability, perhaps necessitating protection from harm or recognition of positive (...) moral and legal rights, particularly if derived from cells of human origin. The use of emergence-based principles in M-CELS development may also create unique challenges, making the technology difficult to fully control or predict in the laboratory as well as in applied medical or environmental settings. In response to these challenges, we argue that the M-CELS community has an obligation to systematically address the ethical and societal aspects of research and to seek input from and accountability to a broad range of stakeholders and publics. As a newly developing field, M-CELS has a significant opportunity to integrate ethically responsible norms and standards into its research and development practices from the start. With the aim of seizing this opportunity, we identify two general kinds of salient ethical issues arising from M-CELS research, and then present a set of commitments to and strategies for addressing these issues. If adopted, these commitments and strategies would help define M-CELS as not only an innovative field, but also as a model for responsible research and engineering. (shrink)

Armed with expanded federal funding for human embryonic stem cell research and new methods for deriving pluripotent stem cells, stem cell researchers in the U.S. are poised to proceed with unprecedented speed toward the development of new clinical therapies. Staring into the new dawn of regenerative medicine, many observers may assume that the only responsible route to the clinic, both scientifically and ethically, is through FDA-approved clinical trials processes. Conventional wisdom dictates that, like pharmaceutical drugs and the use of biological (...) therapeutics, stem cell-based therapies will have to pass through a series of controlled studies — initially to assess safety and toxicity, then efficacy and comparative efficacy — before they can be justifiably administered to patients outside a clinical trials context. (shrink)

To be autonomous, a person must also have authentic moral values. She must act on her own values, not on values that were improperly pressed upon her. To respect a patient's autonomy, then, a caregiver must do more than carry out her requests. The caregiver must honor the patient's authentic requests. But how to do that?

Taking seriously the value of cultural competence in healthcare requires at least three general commitments. First, it involves accepting the view that patients' health beliefs and behaviors are influenced to a significant degree by their own social and cultural practices. Second, it requires careful attention to how health professionals typically respond to patients' different social and cultural standards at various levels of the healthcare delivery system. And third, it calls for developing interventions that are sensitive to these first two issues (...) to assure the delivery of quality healthcare for culturally diverse patients. This much is plain, insofar as we are talking about the broadest of commitments necessary to support the value of cultural competence in healthcare. But what other, more specific commitments are implied in accepting the value of cultural competence? (shrink)

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. Interviews addressed animal welfare and conceptual issues associated with moral status and humanization of nonhuman (...) animals that contain human cells. Our findings suggest that concepts of enhanced moral status and consciousness are not very useful in human–nonhuman‐animal chimeric research in part because their meanings are not easily defined, which presents challenges to applying the concepts in research. Instead, scientists and oversight committee members we interviewed seemed to rely on standard assessments of changes in animal welfare when focusing on the ethics of human‐animal chimeric research. (shrink)

: Many adolescent patients with chronic medical conditions do not manage their illnesses very closely and often put themselves at risk for serious health complications. Setting aside cases of nonadherence that are due to practical difficulties involving the implementation of a management plan, a deeply problematic question remains. How should health care providers respond to adolescent patients who express a conscious and value-driven decision to pursue other goals and interests that are incompatible with their doctors' recommended directives? Using two guiding (...) ethical principles, the "relevant difference principle" and the "principle of noninterference," as well as available empirical data on adolescent decision making and risk perception, the paper concludes that most adolescents ages 14 and older should be allowed to make self-determining decisions regarding the management of their chronic medical conditions. (shrink)

Over the past decade or so, the predominant patient-centered ethos in American bioethics has come under attack by critics who claim that it is morally deficient in certain respects, particularly when viewed in the context of acute-care decisionmaking. One line of criticism has been that the current ethic of patient autonomy gives an individual competent patient far too much decisional authority over the terms of his own treatment so that the patient is at complete liberty to neglect the ways in (...) which his medical decisions can drastically and negatively affect the lives of other family members. Given that family members must help shoulder the financial, emotional, and rehabilitative burdens involved in the patient's care, it has been argued that they too have a legitimate interest in choosing what sort of medical treatment the patient eventually receives. Another closely related line of criticism is that the prevailing focus on patient autonomy gives short shrift to the moral significance of the family as a genuine community. Echoing a view of the person advanced by most communitarian political theorists, some commentators have argued that the patient comes to the clinic so thoroughly embedded in a complex web of familial relationships and obligations that it does not make sense to identify him as the only person in the family to make decisions about treatment. (shrink)

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.

The Brainstorm Organoid Project, funded by the NIH BRAIN Initiative, was designed to position bioethicists to work closely with scientists in identifying potential issues at the earliest stages of human brain organoid research. This proactive and ongoing approach enabled bioethical and scientific collaborators to arrive at conclusions that would have been difficult for either to have discovered alone. One specific example of the benefits of ongoing collaboration was enabling of scientists and bioethicists to work together to facilitate responsible commercialization of (...) neural organoids. This collaborative approach could be a viable model for other science and engineering fields to benefit from contributions through the humanities. (shrink)

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. (shrink)

Brain organoid consciousness remains a remote possibility at this time, yet stem cell research oversight committees and their analogues need concrete guidance rooted in current science to develop a common understanding of salient moral concerns surrounding human brain organoid research. Proposed here is a draft review guide for oversight committees linking the bioethical literature on brain organoid research with present scientific understanding. Subject to ongoing peer assessment and regular revision, this adaptable framework can hopefully help highlight key considerations for review, (...) facilitate committee deliberations, and serve as a useful next step in fostering a transparent, coherent, and just approach to governing brain organoid research at the institutional level. Doing so should better support oversight committees as they strive to collaborate proactively and effectively with investigators to promote ethical brain organoid research and advance beneficial scientific knowledge. (shrink)

Worries about consciousness emerging in vitro in human brain organoids abound in the imaginations of some bioethicists, scientists, and the public. However, these concerns should be allayed once we compare the structural and biological limitations of brain organoids to the anatomical and physiological properties of real human brains that are deemed essential for consciousness. This comparison between the two leads us to conclude that brain organoids are not conscious in any significant way and are unlikely to become so in the (...) foreseeable future. (shrink)

Transplanting disease-specific human brain organoids into animals may offer new insights into psychiatric disorders from a neural mechanistic perspective. This research however may trigger concerns about humanlike consciousness emerging in the brains of grafted animal hosts. Presently, this worry is not scientifically and philosophically warranted. Instead, the principal ethical issue at stake is animal welfare. Given the state of the science and where research is likely to go in the foreseeable future, brain organoid transplantation should proceed while taking animal welfare (...) concerns seriously. (shrink)

Human brain organoid research is a rapidly advancing subfield of stem cell science where researchers are building realistic in vitro brain models through key bioengineering advancements. Despite its enormous potential, this form of research could raise ethical concerns around the moral status of large, complex human brain models and the ethical boundaries that should exist when manipulating increasingly realistic bioengineered constructs. The chapters in this book address issues that, together, complement a desire to see human brain organoid research proceed with (...) scientific and ethical rigor. Responsible progress will require ongoing collaboration between scientists and non-scientists, stem cell biologists and philosophers, bioengineers and policy experts, commercial developers and regulators, and many others. A collaborative bioethics approach can help foster greater awareness, understanding, and guidance for future management of ethical issues surrounding brain organoid research. (shrink)

Brain organoids are small stem cell-derived, self-organizing models of specific brain regions that offer researchers new ways to study the human brain. Since their scientific debut over ten years ago, brain organoids have been used to generate tractable new bioengineered tools for understanding functional interconnectivity of the human brain, dysfunction involved in many neurodegenerative diseases, and certain molecular mechanisms underlying cognition. Despite this field’s considerable scientific promise, advances in human brain organoid research also raise novel philosophical questions and ethical concerns (...) around the use of complex human brain models and the ethical boundaries that should exist when manipulating increasingly realistic bioengineered brain constructs. As researchers generate more realistic organoids in vitro that resemble human brains, it is critically important to understand what ethical boundaries may exist and where researchers and regulators should draw the line for research, both to reduce uncertainties over which projects to pursue in the lab and to address future concerns regulators and the public may harbor about whether this research, if left unexamined, could inadvertently undermine public trust in science. This proposed book delves into ongoing and proactive ethical discussions among ethicists and the neuroscientists involved with this cutting-edge work. Its ultimate goal is to foster greater awareness, understanding, and guidance for future management of ethical issues that may be unique to new areas of brain organoid research. This volume is the result of a close partnership between ethicists and scientists, each informing the other through a collaborative process of joint bioethical deliberation. (shrink)

Research suggests that cloning is incapable of producing a viable embryo when it is used on primate eggs. In fact, the entity created may not qualify as an embryo at all. If the results stand, cloning avoids the moral objections typically lodged against it, and cloning is itself an “alternative source” of stem cells.