Weighing the moral status of brain organoids and research animals.

Recent advances in human brain organoid systems have raised serious worries about the possibility that these in vitro 'mini-brains' could develop sentience, and thus, moral status. This article considers the relative moral status of sentient human brain organoids and research animals, examining whether we have moral reasons to prefer using one over the other. It argues that, contrary to common intuitions, the wellbeing of sentient human brain organoids should not be granted greater moral consideration than the wellbeing of nonhuman research animals. It does so not by denying that typical humans have higher moral status than animals, but instead by arguing that none of the leading justifications for granting humans higher moral status than nonhuman animals apply to brain organoids. Additionally, it argues that there are no good reasons to be more concerned about the well-being of human brain organoids compared to those generated from other species.

The Parliamentary Inquiry into Mitochondrial Donation Law Reform (Maeve's Law) Bill 2021 in Australia: A Qualitative Analysis.

Recently, Australia became the second jurisdiction worldwide to legalize the use of mitochondrial donation technology. The Mitochondrial Donation Law Reform (Maeve's Law) Bill 2021 allows individuals with a family history of mitochondrial disease to access assisted reproductive techniques that prevent the inheritance of mitochondrial disease. Using inductive content analysis, we assessed submissions sent to the Senate Committee as part of a programme of scientific inquiry and public consultation that informed drafting of the Bill. These submissions discussed a range of bioethical and legal considerations of central importance to the political debate. Significantly, submissions from those with a first-hand experience of mitochondrial disease, including clinicians and those with a family history of mitochondrial disease, were in strong support of this legislation. Those in support of the Bill commended the two-staged approach and rigorous licencing requirements as part of the Bill's implementation strategy. Submissions which outlined arguments against the legislation either opposed the use of these techniques in general or opposed aspects of the implementation strategy in Australia. These findings offer a window into the ethical arguments and perspectives that matter most to those Australians who took part in the Senate inquiry into mitochondrial donation. The insights garnered from these submissions may be used to help refine policy and guidelines as the field progresses.

Response to the ISSCR guidelines on human-animal chimera research.

The International Society for Stem Cell Research (ISSCR) has recently released the 2021 update of its guidelines. The update includes detailed new recommendations on human-animal chimera research. This paper argues that the ISSCR recommendations fail to address the core ethical concerns raised by neurological chimeras-namely, concerns about moral status. In minimising moral status concerns, the ISSCR both breaks rank with other major reports on human-animal chimera research and rely on controversial claims about the grounds of moral status that many people will rightly reject. A more robust framework for regulating human-animal chimera research still needs to be developed.

Ethics of Buying DNA.

DNA databases have significant commercial value. Direct-to-consumer genetic testing companies have built databanks using samples and information voluntarily provided by customers. As the price of genetic analysis falls, there is growing interest in building such databases by paying individuals for their DNA and personal data. This paper maps the ethical issues associated with private companies paying for DNA. We outline the benefits of building better genomic databases and describe possible concerns about crowding out, undue inducement, exploitation, and commodification. While certain objections deserve more empirical and philosophical investigation, we argue that none currently provide decisive reasons against using financial incentives to secure DNA samples.

Moving from 'fully' to 'appropriately' informed consent in genomics: The PROMICE framework.

Genomic sequencing technologies (GS) pose novel challenges not seen in older genetic technologies, making traditional standards for fully informed consent difficult or impossible to meet. This is due to factors including the complexity of the test and the broad range of results it may identify. Meaningful informed consent is even more challenging to secure in contexts involving significant time constraints and emotional distress, such as when rapid genomic testing (RGS) is performed in neonatal intensive care units. In this article, we propose that informed consent matters not for its own sake, but because obtaining it furthers a range of morally important goals, such as promoting autonomy, well-being, and trust in medicine. These goals form the basis of a new framework [PROmoting Morally Important Consent Ends (PROMICE)] for assessing the ethical appropriateness of various informed consent models. We illustrate this framework with two examples: (a) a tiered and layered consent model for obtaining consent for GS, and (b) consent for RGS in critically ill newborns. We conclude that appropriately-rather than fully-informed consent provides the correct standard for genomic medicine and research.

The Moral Superiority of Bioengineered Wombs and Ectogenesis for Absolute Uterine Factor Infertility.

This paper argues that uterine transplants are a potentially dangerous distraction from the development of alternative methods of providing reproductive options for women with absolute uterine factor infertility (AUFI). We consider two alternatives in particular: the bioengineering of wombs using stem cells (which would carry fewer risks than uterine transplants) and ectogenesis (which would not require surgical intervention for either the prospective mother with AUFI or a womb donor). Whether biologically or mechanically engineered, these womb replacements could provide a way for women to have children, including genetically related offspring for those who would value this possibility. Most importantly, this alternative would avoid the challenge of sourcing wombs for transplant, a practice that we argue would likely be exploitative and unethical. Continued research into bioengineering and ectogenesis will therefore remain morally important despite the recent development of uterine transplantation, even if the procedure reaches routine clinical application.

Old Challenges or New Issues? Genetic Health Professionals' Experiences Obtaining Informed Consent in Diagnostic Genomic Sequencing.

BACKGROUND: While integrating genomic sequencing into clinical care carries clear medical benefits, it also raises difficult ethical questions. Compared to traditional sequencing technologies, genomic sequencing and analysis is more likely to identify unsolicited findings (UF) and variants that cannot be classified as benign or disease-causing (variants of uncertain significance; VUS). UF and VUS pose new challenges for genetic health professionals (GHPs) who are obtaining informed consent for genomic sequencing from patients. METHODS: We conducted semi-structured interviews with 31 GHPs across Europe, Australia and Canada to identify some of these challenges. RESULTS: Our results show that GHPs find it difficult to prepare patients to receive results because a vast amount of information is required to fully inform patients about VUS and UF. GHPs also struggle to engage patients - many of whom may be focused on ending their 'diagnostic odyssey' - in the informed consent process in a meaningful way. Thus, some questioned how 'informed' patients actually are when they agree to undergo clinical genomic sequencing. CONCLUSIONS: These findings suggest a tension remains between sufficient information provision at the risk of overwhelming the patient and imparting less information at the risk of uninformed decision-making. We suggest that a shift away from 'fully informed consent' toward an approach aimed at realizing, as far as possible, the underlying goals that informed consent is meant to promote.

Emerging moral status issues.

Many controversies in bioethics turn on questions of moral status. Some moral status issues have received extensive bioethical attention, including those raised by abortion, embryo experimentation, and animal research. Beyond these established debates lie a less familiar set of moral status issues, many of which are tied to recent scientific breakthroughs. This review article surveys some key developments that raise moral status issues, including the development of in vitro brains, part-human animals, "synthetic" embryos, and artificial womb technologies. It introduces the papers in this Special Issue, contextualises their contributions to the moral status literature, and highlights some enduring challenges of determining the moral status of novel types of beings.

'It's not worse than eating them': the limits of analogy in bioethics.

Bioethicists often defend novel practices by drawing analogies with practices that we are already familiar with and currently tolerate. If some novel practice is less bad than some widely-accepted practice, then (it is argued) we cannot rightly reject it. Using the bioethics literature on xenotransplantation and interspecies blastocyst complementation as a case study, I show how this style of argument can go awry. The key problem is that our moral intuitions about familiar practices can be distorted by their seeming normality. When considering the ethics of emerging technologies and novel practices, we should remain open to the possibility that our moral views about familiar practices are mistaken.

The Duty to Look for Incidental Findings in Imaging Research.

Imaging research regularly yields incidental findings that may have personal medical or reproductive decision-making significance to study participants. It is widely assumed that researchers have a moral obligation to disclose at least some kinds of incidental findings to research participants. However, it is also a widely held view that researchers do not have a moral obligation to actively look for abnormalities irrelevant to the aims of their study. This paper challenges that assumption.

Why genomics researchers are sometimes morally required to hunt for secondary findings.

BACKGROUND: Genomic research can reveal 'unsolicited' or 'incidental' findings that are of potential health or reproductive significance to participants. It is widely thought that researchers have a moral obligation, grounded in the duty of easy rescue, to return certain kinds of unsolicited findings to research participants. It is less widely thought that researchers have a moral obligation to actively look for health-related findings (for example, by conducting additional analyses to search for findings outside the scope of the research question). MAIN TEXT: This paper examines whether there is a moral obligation, grounded in the duty of easy rescue, to actively hunt for genomic secondary findings. We begin by showing how the duty to disclose individual research findings can be grounded in the duty of easy rescue. Next, we describe a parallel moral duty, also grounded in the duty of easy rescue, to actively hunt for such information. We then consider six possible objections to our argument, each of which we find unsuccessful. Some of these objections provide reason to limit the scope of the duty to look for secondary findings, but none provide reason to reject this duty outright. CONCLUSIONS: We argue that under a certain range of circumstances, researchers are morally required to hunt for these kinds of secondary findings. Although these circumstances may not currently obtain, genomic researchers will likely acquire an obligation to hunt for secondary findings as the field of genomics continues to evolve.

Ethical issues in uterine transplantation.

Despite a recent surge of bioethical attention, ethical analysis of uterine transplantation is still in its early stages, and many of the key ethical issues remain underexamined and unresolved. In this paper, we briefly review some key ethical issues associated with uterine transplantation (beyond those associated with organ transplantation more generally). We structure our discussion in terms of Beauchamp and Childress' four principles of biomedical ethics: beneficence, non-maleficence, autonomy, and justice. Our review highlights some ethical questions that require further bioethical attention before uterine transplantation can be fully embraced as a potential treatment for absolute uterine factor infertility. We close by arguing that the costs and benefits of uterine transplantation need to be considered in the context of other possible treatments for absolute uterine factor infertility and alternative methods of family creation.

Germline gene editing and the precautionary principle.

The precautionary principle aims to influence decision-making in contexts where some activity poses uncertain but potentially grave threats. This perfectly describes the controversy surrounding germline gene editing. This article considers whether the precautionary principle should influence how we weigh the risks and benefits of human germline interventions, focusing especially on the possible threats to the health of future generations. We distinguish between several existing forms of the precautionary principle, assess their plausibility and consider their implications for the ethics of germline modification. We also offer a novel form of the precautionary principle: the sufficientarian precautionary principle. Some plausible versions of the precautionary principle recommend placing somewhat greater weight on avoiding threats to future generations than on achieving short-term benefits. However, no plausible versions of the precautionary principle entail that we should outright reject the use germline gene editing in human reproduction and some, such as the sufficientarian version, might endorse its use.

Time to rethink the law on part-human chimeras.

It may soon be possible to generate human tissues and organs inside of part-human chimeras via a technique known as interspecies blastocyst complementation. Using Australian legislation as a case study, we show why this technique of creating part-human chimeras falls within the gaps of existing legislation. We give an overview of the key ethical issues raised by part-human chimera research, and we describe how well these issues are met by a range of possible regulatory approaches. We ultimately argue that regulation of part-human chimera research should be (re)designed to balance two key aims: to facilitate ethical research involving part-human chimeras and to prevent unethical experimentation with chimeras that have an uncertain-and potentially substantial-degree of moral status.

Human-Animal Chimeras: The Moral Insignificance of Uniquely Human Capacities.

Human-animal chimeras-creatures composed of a mix of animal and human cells-have come to play an important role in biomedical research, and they raise ethical questions. This article focuses on one particularly difficult set of questions-those related to the moral status of human-animal chimeras with brains that are partly or wholly composed of human cells. Given the uncertain effects of human-animal chimera research on chimeric animals' cognition, it would be prudent to ensure we do not overlook or underestimate their moral status. However, to assess moral status, we first need to determine what kinds of capacities are morally relevant. The standard view holds that it matters, morally, if chimeric animals develop uniquely human cognitive capacities. I argue that this view is mistaken, highlighting three problems with it: that we can think of examples of uniquely human cognitive capacities that are not morally significant, that we can think of examples of morally significant cognitive capacities that are not uniquely human, and that evidence that some cognitive capacity is shared with nonhuman animals does not undermine claims that this capacity is morally significant. We need a better framework for thinking about the moral status of part-human beings.

Moral Limits of Brain Organoid Research.

Brain organoid research raises ethical challenges not seen in other forms of stem cell research. Given that brain organoids partially recapitulate the development of the human brain, it is plausible that brain organoids could one day attain consciousness and perhaps even higher cognitive abilities. Brain organoid research therefore raises difficult questions about these organoids' moral status - questions that currently fall outside the scope of existing regulations and guidelines. This paper shows how these gaps can be addressed. We outline a moral framework for brain organoid research that can address the relevant ethical concerns without unduly impeding this important area of research.

Commodification and Human Interests.

In Markets Without Limits and a series of related papers, Jason Brennan and Peter Jaworski argue that it is morally permissible to buy and sell anything that it is morally permissible to possess and exchange outside of the market. Accordingly, we should (Brennan and Jaworski argue) open markets in "contested commodities" including blood, gametes, surrogacy services, and transplantable organs. This paper clarifies some important aspects of the case for market boundaries and in so doing shows why there are in fact moral limits to the market. I argue that the case for restricting the scope of the market does not (as Brennan and Jaworski assume) turn on the idea that some things are constitutively non-market goods; it turns instead on the idea that treating some things according to market norms would threaten the realization of particular kinds of human interests.

Beyond Fair Benefits: Reconsidering Exploitation Arguments Against Organ Markets.

One common objection to establishing regulated live donor organ markets is that such markets would be exploitative. Perhaps surprisingly, exploitation arguments against organ markets have been widely rejected in the philosophical literature on the subject. It is often argued that concerns about exploitation should be addressed by increasing the price paid to organ sellers, not by banning the trade outright. I argue that this analysis rests on a particular conception of exploitation (which I refer to as 'fair benefits' exploitation), and outline two additional ways that the charge of exploitation can be understood (which I discuss in terms of 'fair process' exploitation and complicity in injustice). I argue that while increasing payments to organ sellers may mitigate or eliminate fair benefits exploitation, such measures will not necessarily address fair process exploitation or complicity in injustice. I further argue that each of these three forms of wrongdoing is relevant to the ethics of paid living organ donation, as well as the design of public policy more generally.