Ilar Journal最新文献

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.

Researchers have worked with animals as models for decades to expand our knowledge of basic biological processes and to systematically study the physiology of disease. In general, the public has an expectation that work with animals has a purpose and will ultimately reap benefits. The likelihood of such an outcome is directly dependent on the quality of the science being conducted with those animals. However, not all frameworks for consideration of the ethics around animal research overtly consider scientific quality. In the following review, we explore the complex relationship between scientific quality and animal research ethics. We advocate for the development of a detailed "Harm-Yield Analysis" for the evaluation of biomedical animal research that emphasizes scientific quality along with societal benefit in the ethical justification of the research. We reflect on the lost opportunity to establish best practices in animal research early in the career of scientists by introducing in the curriculum and encouraging the use of a paradigm of the iterative consideration of the ethics of animal research alongside other aspects of experimental design.

Harm-benefit analyses (HBAs) are becoming de rigueur with some governmental regulatory agencies and popular with local institutional animal care and use committees (or their equivalents), the latter due, in part, to the adoption of HBAs as an international accreditation standard. Such analyses are employed as an attempt to balance potential or actual pain or distress imposed on laboratory animals against scientists' justifications for those impositions. The outcomes of those analyses are then supposed to be included in an official assessment of whether a given animal protocol should be approved as proposed. While commendable in theory as a means to avoid or minimize animal suffering, HBAs come with a flawed premise. Establishing an accurate prediction of benefit, especially for so-called "basic" research (vs "applied" research, such as in vivo testing for product development or batch release), is often impossible given the uncertain nature of experimental outcomes and the eventual value of those results. That impossibility, in turn, risks disapproving a legitimate research proposal that might have yielded important new knowledge if it had been allowed to proceed. Separately, the anticipated harm to which the animal would be subjected should similarly be scrutinized with an aim to refine that harm regardless of purported benefits if the protocol is approved. The intentions of this essay are to reflect on the potential harm and benefit of the HBA itself, highlight how HBAs may be helpful in advancing refinements, and propose alternative approaches to both parts of the equation in the assessment process.

Marmosets and closely related tamarins have become popular models for understanding aspects of human brain organization and function because they are small, reproduce and mature rapidly, and have few cortical fissures so that more cortex is visible and accessible on the surface. They are well suited for studies of development and aging. Because marmosets are highly social primates with extensive vocal communication, marmoset studies can inform theories of the evolution of language in humans. Most importantly, marmosets share basic features of major sensory and motor systems with other primates, including those of macaque monkeys and humans with larger and more complex brains. The early stages of sensory processing, including subcortical nuclei and several cortical levels for the visual, auditory, somatosensory, and motor systems, are highly similar across primates, and thus results from marmosets are relevant for making inferences about how these systems are organized and function in humans. Nevertheless, the structures in these systems are not identical across primate species, and homologous structures are much bigger and therefore function somewhat differently in human brains. In particular, the large human brain has more cortical areas that add to the complexity of information processing and storage, as well as decision-making, while making new abilities possible, such as language. Thus, inferences about human brains based on studies on marmoset brains alone should be made with a bit of caution.

The publication of reproducible, replicable, and translatable data in studies utilizing animal models is a scientific, practical, and ethical necessity. This requires careful planning and execution of experiments and accurate reporting of results. Recognition that numerous developmental, environmental, and test-related factors can affect experimental outcomes is essential for a quality study design. Factors commonly considered when designing studies utilizing aquatic animal species include strain, sex, or age of the animal; water quality; temperature; and acoustic and light conditions. However, in the aquatic environment, it is equally important to consider normal species behavior, group dynamics, stocking density, and environmental complexity, including tank design and structural enrichment. Here, we will outline normal species and social behavior of 2 commonly used aquatic species: zebrafish (Danio rerio) and Xenopus (X. laevis and X. tropicalis). We also provide examples as to how these behaviors and the complexity of the tank environment can influence research results and provide general recommendations to assist with improvement of reproducibility and replicability, particularly as it pertains to behavior and environmental complexity, when utilizing these popular aquatic models.

Environmental complexity is an experimental paradigm as well as a potential part of animals' everyday housing experiences. In experimental uses, researchers add complexity to stimulate brain development, delay degenerative brain changes, elicit more naturalistic behaviors, and test learning and memory. Complexity can exacerbate or mitigate behavioral problems, give animals a sense of control, and allow for expression of highly driven, species-typical behaviors that can improve animal welfare. Complex environments should be designed thoughtfully with the animal's natural behaviors in mind, reported faithfully in the literature, and evaluated carefully for unexpected effects.

For more than 50 years, the research community has made strides to better determine the nutrient requirements for many common laboratory animal species. This work has resulted in high-quality animal feeds that can optimize growth, maintenance, and reproduction in most species. We have a much better understanding of the role that individual nutrients play in physiological responses. Today, diet is often considered as an independent variable in experimental design, and specialized diet formulations for experimental purposes are widely used. In contrast, drinking water provided to laboratory animals has rarely been a consideration in experimental design except in studies of specific water-borne microbial or chemical contaminants. As we advance in the precision of scientific measurements, we are constantly discovering previously unrecognized sources of experimental variability. This is the nature of science. However, science is suffering from a lack of experimental reproducibility or replicability that undermines public trust. The issue of reproducibility/replicability is especially sensitive when laboratory animals are involved since we have the ethical responsibility to assure that laboratory animals are used wisely. One way to reduce problems with reproducibility/replicability is to have a strong understanding of potential sources of inherent variability in the system under study and to provide "…a clear, specific, and complete description of how the reported results were reached [1]." A primary intent of this review is to provide the reader with a high-level overview of some basic elements of laboratory animal nutrition, methods used in the manufacturing of feeds, sources of drinking water, and general methods of water purification. The goal is to provide background on contemporary issues regarding how diet and drinking water might serve as a source of extrinsic variability that can impact animal health, study design, and experimental outcomes and provide suggestions on how to mitigate these effects.