Neuroethics and Animals: Report and Recommendations From the University of Pennsylvania Animal Research Neuroethics Workshop.

Growing awareness of the ethical implications of neuroscience in the early years of the 21st century led to the emergence of the new academic field of "neuroethics," which studies the ethical implications of developments in the neurosciences. However, despite the acceleration and evolution of neuroscience research on nonhuman animals, the unique ethical issues connected with neuroscience research involving nonhuman animals remain underdiscussed. This is a significant oversight given the central place of animal models in neuroscience. To respond to these concerns, the Center for Neuroscience and Society and the Center for the Interaction of Animals and Society at the University of Pennsylvania hosted a workshop on the "Neuroethics of Animal Research" in Philadelphia, Pennsylvania. At the workshop, expert speakers and attendees discussed ethical issues arising from neuroscience research involving nonhuman animals, including the use of animal models in the study of pain and psychiatric conditions, animal brain-machine interfaces, animal-animal chimeras, cerebral organoids, and the relevance of neuroscience to debates about personhood. This paper highlights important emerging ethical issues based on the discussions at the workshop. This paper includes recommendations for research in the United States from the authors based on the discussions at the workshop, loosely following the format of the 2 Gray Matters reports on neuroethics published by the Presidential Commission for the Study of Bioethical Issues.

Understanding childbirth pain in Brazilian women: A qualitative descriptive study.

BACKGROUND: The pain associated with childbirth is a cause of severe pain, and the literature suggests that it can be influenced by psychosocial influences, the environment, and cognitive processes, creating the overall experience of childbirth. Therefore, the investigation of women's childbirth pain experience is essential. AIM: The purpose of this study is to understand women's childbirth pain and determine which influences can contribute to building different experiences. METHOD: A qualitative descriptive approach was adopted to explore the women's childbirth pain experiences, by understanding the influences on their experiences. Data were collected through in-depth interviews with 21 women in a hospital setting in São Paulo, Brazil, and analysed by thematic analysis. RESULTS: Three major themes emerged from the analysis: (1) experiencing childbirth pain, (2) face-to-face with pain, and (3) empowerment needs. DISCUSSION: Many factors influence how Brazilian women manage pain and shape their experience during childbirth. The findings suggest that when women had a positive experience, they asked for minimal support, demonstrated balance, and expressed that the pain was manageable; when they had unfavourable experiences, they regarded pain as a threat and a punishment and associated it with unpleasant emotions. CONCLUSION: The results outlined concerns that should be addressed in the provision of specific, appropriate care for women, to support them in improving their experience during childbirth.

A Belmont Report for Animals?

Human and animal research both operate within established standards. In the United States, criticism of the human research environment and recorded abuses of human research subjects served as the impetus for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the resulting Belmont Report. The Belmont Report established key ethical principles to which human research should adhere: respect for autonomy, obligations to beneficence and justice, and special protections for vulnerable individuals and populations. While current guidelines appropriately aim to protect the individual interests of human participants in research, no similar, comprehensive, and principled effort has addressed the use of (nonhuman) animals in research. Although published policies regarding animal research provide relevant regulatory guidance, the lack of a fundamental effort to explore the ethical issues and principles that should guide decisions about the potential use of animals in research has led to unclear and disparate policies. Here, we explore how the ethical principles outlined in the Belmont Report could be applied consistently to animals. We describe how concepts such as respect for autonomy and obligations to beneficence and justice could be applied to animals, as well as how animals are entitled to special protections as a result of their vulnerability.

Public attitudes toward genetic modification in dairy cattle.

Genetic modification has been used to create dairy cattle without horns and with increased resistance to disease; applications that could be beneficial for animal welfare, farm profits, and worker safety. Our aim was to assess how different stated purposes were associated with public attitudes toward these two applications using a mixed methods approach. Using an online survey, U.S. participants were randomly assigned to one of ten treatments in a 2 (application: hornless or disease-resistant) x 5 (purposes: improved animal welfare, reduced costs, increased worker safety, all three purposes, or no purpose) factorial design. Each participant was asked to read a short description of the assigned treatment (e.g. hornlessness to improve calf welfare) and then respond to a series of questions designed to assess attitude toward the treatment using 7-point Likert scales (1 = most negative; 7 = most positive). Responses of 957 participants were averaged to creative an attitude construct score. Participants were also asked to explain their response to the treatment. Qualitative analysis of these text responses was used to identify themes associated with the participants' reasoning. Participant attitudes were more favorable to disease resistance than to hornlessness (mean ± SE attitude score: 4.5 ± 0.15 vs. 3.7 ± 0.14). In the 'disease-resistance' group participants had more positive attitudes toward genetic modification when the described purpose was animal welfare versus reduction of costs (contrast = 1.00; 95% CI = 0.12-1.88). Attitudes were less favorable to the 'hornless' application if no purpose was provided versus when the stated purpose was either to improve animal welfare (contrast = 0.95; 95% CI = 0.26-1.64) or when all purposes were provided (contrast = 0.88; 95% CI = 0.19-1.58). Similarly, attitudes were less positive when the stated purpose was to reduce costs versus either improving animal welfare (contrast = 0.86; 95% CI = 0.09-1.64) or when all purposes were provided (contrast = 0.79; 95% CI = 0.02-1.56). Quantitative and qualitative analysis indicated that both the specific application and perceived purpose (particularly when related to animal welfare) can affect public attitudes toward genetic modification.

Public attitudes towards genetically modified polled cattle.

Genetic modification of farm animals has not been well accepted by the public. Some modifications have the potential to improve animal welfare. One such example is the use of gene editing (i.e. CRISPR (clustered regularly interspaced short palindromic repeats)) to spread the naturally occurring POLLED gene, as these genetically hornless animals would not need to experience the painful procedures used to remove the horns or horn buds. The aim of the current study was to assess public attitudes regarding the use of GM to produce polled cattle. United States (US) citizens (n = 598), recruited via Amazon Mechanical Turk, were asked "Do you think genetically modifying cows to be hornless would be…", and responded using a 7-point Likert scale (1 = a very bad thing, 4 = neither good nor bad, 7 = a very good thing). Participants were then asked to indicate if they would be willing to consume products from these modified animals. We excluded 164 of the original 598 participants for not completing the survey, failing any of three attention check questions, or providing no or unintelligible qualitative responses. Respondents were then asked to provide a written statement explaining their answers; these reasons were subjected to qualitative analysis. Comparison of Likert scale ratings between two groups was done using the Wilcoxon rank-sum test, and comparisons between more than two groups were done using the Kruskal-Wallis rank test. More people responded that the modification would be good (Likert ≥ 5; 65.7%) than bad (Likert ≤ 3; 23.1%), and that they would be willing to consume products from these animals (Likert ≥ 5; 66.0%) versus not consume these products (Likert ≤ 3; 22.6%). Qualitative analysis of the text responses showed that participant reasoning was based on several themes including animal welfare, uncertainty about the technology, and worker well-being. In conclusion, many participants reported positive attitudes towards GM polled cattle; we suggest that people may be more likely to support GM technologies when these are perceived to benefit the animal.

Behavioural discrimination of noxious stimuli in infants is dependent on brain maturation.

Changes in facial expression are an essential form of social communication and in nonverbal infants are often used to alert care providers to pain-related distress. However, studies of early human brain development suggest that premature infants aged less than 34 weeks' gestation do not display discriminative brain activity patterns to equally salient noxious and innocuous events. Here we examine the development of facial expression in 105 infants, aged between 28 and 42 weeks' gestation. We show that the presence of facial expression change after noxious and innocuous stimulation is age-dependent and that discriminative facial expressions emerge from approximately 33 weeks' gestation. In a subset of 49 infants, we also recorded EEG brain activity and demonstrated that the temporal emergence of facial discrimination mirrors the developmental profile of the brain's ability to generate discriminative responses. Furthermore, within individual infants, the ability to display discriminative facial expressions is significantly related to brain response maturity. These data demonstrate that the emergence of behavioural discrimination in early human life corresponds to our brain's ability to discriminate noxious and innocuous events and raises fundamental questions as to how best to interpret infant behaviours when measuring and treating pain in premature infants.

Consideration and checkboxes: incorporating ethics and science into the 3Rs.

Members of the research community aim to both produce high-quality research and ensure that harm is minimized in animals. The primary means of ensuring these goals are both met is the 3Rs framework of replacement, reduction, and refinement. However, some approaches to the 3Rs may result in a 'check box mentality' in which IACUC members, researchers, administrators, and caretakers check off a list of tasks to evaluate a protocol. We provide reasons for thinking that the 3Rs approach could be enhanced with more explicit discussion of the ethical assumptions used to arrive at an approved research protocol during IACUC review. Here we suggest that the notion of moral considerability, and all of the related issues it gives rise to, should be incorporated into IACUC discussions of 3Rs deliberations during protocol review to ensure that animal wellbeing is enhanced within the constraints of scientific investigation.

Would the elimination of the capacity to suffer solve ethical dilemmas in experimental animal research?

The use of genetic engineering to enhance the welfare of laboratory animals can reduce the amount of suffering in current neuroscience research paradigms. In particular, for some forms of basic research, we can use welfare-enhanced animals to reduce harms to animals without sacrificing any of the scientific validity. In another group of experiments, we can use welfare-enhanced animals to dramatically reduce the number of unprotected animals enduring aversive procedures. Many of the objections to using welfare-enhanced animals for food production do not apply to their use in research, since genetic knockout techniques are already used routinely in research for human ends and since there is no risk for human health. Furthermore, examples of recent knockout experiments suggest that we already have, or are very close to having, the capacity to reduce suffering in laboratories via genetic engineering. If we are truly committed to balancing the advancement of science with the welfare of animals, this option should be further explored.

The asymmetrical contributions of pleasure and pain to animal welfare.

Recent results from the neurosciences demonstrate that pleasure and pain are not two symmetrical poles of a single scale of experience but in fact two different types of experiences altogether, with dramatically different contributions to well-being. These differences between pleasure and pain and the general finding that "the bad is stronger than the good" have important implications for our treatment of nonhuman animals. In particular, whereas animal experimentation that causes suffering might be justified if it leads to the prevention of more suffering, it can never by justified merely by leading to increased levels of happiness.