Laboratory animal ethics education improves medical students' awareness of laboratory animal ethics.

OBJECTIVE: In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. METHODS: One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. RESULTS: After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P < 0.05. Test scores also showed improvement, with students scoring (93.02 ± 11.65) after education compared to (67.83 ± 8.08) before, a statistically significant difference. CONCLUSIONS: This research helps to provide information for the good practices of laboratory animal ethics education. After receiving laboratory animal ethics education, students are better able to treat laboratory animals in a correct animal ethical manner. Laboratory animal ethics education helps improve students' knowledge of laboratory animal ethics. Students' perception towards how the laboratory animal ethics course should be delivered may vary. Still, new courses or better organized courses on laboratory animal ethics education are required in order to provide students an in-depth understanding.

Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0.

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication.

Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research.

The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.

Publication reform to safeguard wildlife from researcher harm.

Despite abundant focus on responsible care of laboratory animals, we argue that inattention to the maltreatment of wildlife constitutes an ethical blind spot in contemporary animal research. We begin by reviewing significant shortcomings in legal and institutional oversight, arguing for the relatively rapid and transformational potential of editorial oversight at journals in preventing harm to vertebrates studied in the field and outside the direct supervision of institutions. Straightforward changes to animal care policies in journals, which our analysis of 206 journals suggests are either absent (34%), weak, incoherent, or neglected by researchers, could provide a practical, effective, and rapidly imposed safeguard against unnecessary suffering. The Animals in Research: Reporting On Wildlife (ARROW) guidelines we propose here, coupled with strong enforcement, could result in significant changes to how animals involved in wildlife research are treated. The research process would also benefit. Sound science requires animal subjects to be physically, physiologically, and behaviorally unharmed. Accordingly, publication of methods that contravenes animal welfare principles risks perpetuating inhumane approaches and bad science.

Refining animal research: The Animal Study Registry.

The Animal Study Registry (ASR; www.animalstudyregistry.org) was launched in January 2019 for preregistration of animal studies in order to increase transparency and reproducibility of bioscience research and to promote animal welfare. The registry is free of charge and is designed for exploratory and confirmatory studies within applied science as well as basic and preclinical research. The registration form helps scientists plan their study thoroughly by asking detailed questions concerning study design, methods, and statistics. With registration, the study automatically receives a digital object identifier (DOI) that marks it as intellectual property of the researcher. To accommodate the researchers concerns about theft of ideas, users can restrict the visibility of their registered studies for up to 5 years. The full content of the study becomes publicly accessible at the end of the embargo period. Because the platform is embedded in the infrastructure of the German Federal Government, continuity and data security are provided. By registering a study in the ASR, researchers can show their commitment to transparency and data quality to reviewers and editors, to third-party donors, and to the general public.

Public perception of laboratory animal testing: Historical, philosophical, and ethical view.

The use of laboratory animals in biomedical research is a matter of intense public debate. Recent statistics indicates that about half of the western population, sensitive to this discussion, would be in favor of animal testing while the other half would oppose it. Here, outlining scientific, historical, ethical, and philosophical aspects, we provide an integrated view explaining the reasons why biomedical research can hardly abandon laboratory animal testing. In this paper, we retrace the historical moments that mark the relationship between humans and other animal species. Then starting from Darwin's position on animal experimentation, we outline the steps that over time allowed the introduction of laws and rules that regulate animals' use in biomedical research. In our analysis, we present the perspectives of various authors, with the aim of delineating a theoretical framework within which to insert the ethical debate on laboratory animals research. Through the analysis of fundamental philosophical concepts and some practical examples, we propose a view according to which laboratory animals experimentation become ethically acceptable as far as it is guided by the goal of improving humans and other animal species (i.e., pets) life. Among the elements analyzed, there is the concept of responsibility that only active moral subjects (humans) have towards themselves and towards passive moral subjects (other animal species). We delineate the principle of cruelty that is useful to understand why research in laboratory animals should not be assimilated to a cruel act. Moreover, we touch upon the concepts of necessity and "good cause" to underline that, if biomedical research would have the possibility to avoid using animals, it would surely do that. To provide an example of the negative consequences occurring from not allowing laboratory animal research, we analyze the recent experience of Covid-19 epidemic. Finally, recalling the principle of "heuristics and biases" by Kahneman, we discuss why scientists should reconsider the way they are conveying information about their research to the general public.

Preclinical screening for antidepressant activity - shifting focus away from the Forced Swim Test to the use of translational biomarkers.

Depression is the world's predominant mental health problem and a leading cause of disability. Neuropharmacological research has not yet advanced treatments to sufficiently meet clinical need, largely due to the failure of animal models to predict clinical efficacy. The forced swim test (FST) has been extensively used in the field of antidepressant research but has been under scrutiny due to its perceived severity to animals. Any use of animals in experiments and testing must have a scientific or regulatory purpose and researchers need to ensure that there is no scientifically valid alternative. However, regulatory requirements have been incorrectly cited as a reason to support the use of the FST. More research is required on tests that do not involve stressing animals as replacements for the FST. Non-behavioural neurochemical measures might provide a means to advance neuropharmacological developments while reducing animal suffering. For example, brain-derived neurotrophic factor (BDNF) may be promising.

Animal research unbound: The messiness of the moral and the ethnographer's dilemma.

Interspecies intimacy defines an inescapable reality of lab animal research. This essay is an effort to disentangle this reality's consequences-both in and outside the lab-as framed by the quandaries of ethnographic engagement. Encounters with lab staff and, in turn, with audiences unfamiliar with laboratory life, together provide crucial entry points for considering how the "messiness of the moral" might facilitate an "unbounded" approach to lab animal worlds. Within the lab, one encounters specialized ethical principles-often codified as law-that delimit strict boundaries of in/appropriate human thought and action. Such principles determine quotidian practices of welfare and care that, in peculiar ways, privilege animal health (as key to reliable data) while obscuring, erasing, or denying human forms of self care. As such, they presuppose a regulatory ability to formulate, shape, and (re)direct human action. Yet attentiveness to the "messiness of the moral" of lab work exposes other realities: indeed, lab personnel regularly engage in a host of subversive responses that test or cross the boundaries of mandated behavior that (re)invigorate the meaning of moral acts of care as interspecies responsibility. The ethnographer's ability to witness, record, and write about these actions within the lab rests comfortably on the relativist principle of suspended judgment. Once one moves outside the lab, however, I ask, wherein lies ethnographic responsibility, when one's accounts of the moral messiness of quotidian lab practices become unbounded and go public? I argue that a dialectical inter- and intraspecies framework-inspired by the existential anthropologist Michael Jackson-offers the ethnographer (and still other scholars) possibilities for forging a productively "unbounded" methodological analytic in and beyond domains of animal science.

Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research.

In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.

In the name of science: animal appellations and best practice.

BACKGROUND: The practice of giving animal research subjects proper names is frowned on by the academic scientific community. While researchers provide a number of reasons for desisting from giving their animal subjects proper names, the most common are that (1) naming leads to anthropomorphising which, in turn, leads to data and results that are unobjective and invalid; and (2) while naming does not necessarily entail some mistake on the researcher's part, some feature of the research enterprise renders the practice impossible or ill-advised. OBJECTIVES: My aim is to assess whether the scientific community's attitude towards naming animal research subjects is justified. That is, I wish to consider whether the practice of naming animal research subjects is good or bad for the purposes of scientific research. METHOD: After reviewing the extant literature, I constructed a list of the main arguments researchers provide for desisting from naming their animal research subjects. I then analysed these arguments, with a view to determining whether they in fact provide good reasons to avoid naming animal research subjects. CONCLUSION: I argue that none of the aforementioned reasons usually provide good grounds for not naming animal research subjects. Moreover, there are usually powerful reasons in favour of researchers giving their research animals proper names. This is because the practice usually leads to greater empathy and so to improved animal well-being. This, in turn, leads to better animal science. Thus, the scientific community's attitude towards naming animal research subjects is not justified.

Good Research Practice: Lessons from Animal Care and Use.

Animal care and use play a pivotal role in the research process. Ethical concerns on the use of animals in research have promoted the creation of a legal framework in many geographical areas that researchers must comply with, and professional organizations continuously develop recommendations on specific areas of laboratory animal science. Scientific evidence demonstrates that many aspects of animal care and use which are beyond the legal requirements have direct impact on research results. Therefore, the review and oversight of animal care and use programs are essential to identify, define, control, and improve all of these aspects to promote the reproducibility, validity, and translatability of animal-based research outcomes. In this chapter, we summarize the ethical principles driving legislation and recommendations on animal care and use, as well as some of these laws and international recommendations. Examples of the impact of specific animal care and use aspects on research, as well as systems of internal and external oversight of animal care and use programs, are described.

Are the Lives of Animals Well-spent in Laboratory Science Research? A Study of Orthopaedic Animal Studies in Turkey.

BACKGROUND: As in all fields of medicine, animal studies are widely performed in orthopaedics and have increased in number over time. However, it is not clear to what extent these studies provide a basis for future research or advancements in clinical science. Concerns about the reliability and translational ability of animal studies have been reported, and major orthopaedic journals and organizations are encouraging the reduction of unnecessary experiments on animals. QUESTION/PURPOSES: (1) What proportion of animal studies conducted for orthopaedic research in Turkey were never published? And of those that were published, how long did it take to publish? (2) What proportion of those studies were published in journals with an Impact Factor of 2 or more? (3) What proportion of those published papers were never cited or cited only once? (4) What was the contribution to science of an animal euthanized for orthopaedic research in Turkey? METHODS: We reviewed all oral and poster presentations at the Turkish National Congress of Orthopaedics and Traumatology from 2009 to 2017 (retrieved from the archives of Acta Orthopaedica et Traumatologica Turcica), as well as all postgraduate theses in orthopaedics from 1991 to 2017 (retrieved from the archives of the National Thesis Center of the Council of Higher Education) to identify all orthopaedic studies that involved animals. We searched the keywords "animal studies," "experimental studies," and "orthopaedics" in these archives. We defined animal research as orthopaedic studies based on animal models. From this search and using that definition, 252 studies were identified. Of those, 4% (9) were excluded as they were thesis studies with no abstract in the archives. Thus, a total of 243 animal studies performed in Turkey were included for analysis in this retrospective study. The abstracts of these studies were examined to determine the study model (such as bone fracture models, tendon healing models, cartilage models) and number of euthanized animals. Between 1991 and 2017, 9412 vertebrate animals were euthanized for these studies. We searched PubMed, Google Scholar, ResearchGate, and ORCID to determine whether these papers were subsequently published, in which journal, and how long after the initial presentation publication occurred. The Web of Science 2019 database was used to determine the Impact Factor of the journals, the total citation count of each study, and the mean annual citation for each study (citations per year). For purposes of this analysis, we divided journals into those with an Impact Factor of 2 or more, 4 or more, and those with an Impact Factor below 2. The mean annual citation per euthanized animal (citations per animal per year) was calculated to determine the contribution of a euthanized animal to science. RESULTS: A total of 42% (101 of 243) of the animal studies in Turkey were never published. For all published studies, the mean time to publication was 2.2 ± 2.6 years (95% CI 1.7 to 2.6). The proportion of studies published in orthopaedic journals with an Impact Factor of 2 or more was 14% (34 of 243). Among the 142 published papers, 38% (54) were either never cited or were cited only once, and the mean citations per year was 1.1 ± 1.7 (95% CI 0.7 to 1.3). The mean citations per animal/year among the 142 published studies was 0.03 ± 0.04 (95% CI 0.02 to 0.04). CONCLUSION: In the 243 theses and national congress presentations, 9412 animals were euthanized. Based on the low percentage of papers using animals that were euthanized and the very low proportion of studies published in higher-Impact Factor journals or garnering more than a single citation, in aggregate, little seems to have been gained from the loss of animal life. Future studies should try to replicate or refute our results in other countries. CLINICAL RELEVANCE: Orthopaedic researchers should try to reduce their use of unnecessary animal studies, for example, by reporting on the use of the "3Rs" (replacement, reduction, and refinement) in the development of an animal study design, as well as through following universal guidelines so that a study might have a clinical impact. Researchers should not conduct an animal study until they are convinced that the expected results are quite likely to deliver substantial benefit to people or to advance science in a meaningful way; although this seems intuitive, our results suggest that this may not be taking place. Ethics committees in Turkey should consider more detailed questioning before approving animal studies. If our results are replicated elsewhere, then a broader look at how these approvals are conducted should be performed.

Ethical arguments concerning human-animal chimera research: a systematic review.

BACKGROUND: The burgeoning field of biomedical research involving the mixture of human and animal materials has attracted significant ethical controversy. Due to the many dimensions of potential ethical conflict involved in this type of research, and the wide variety of research projects under discussion, it is difficult to obtain an overview of the ethical debate. This paper attempts to remedy this by providing a systematic review of ethical reasons in academic publications on human-animal chimera research. METHODS: We conducted a systematic review of the ethical literature concerning human-animal chimeras based on the research question: "What ethical reasons have been given for or against conducting human-animal chimera research, and how have these reasons been treated in the ongoing debate?" Our search extends until the end of the year 2017, including MEDLINE, Embase, PhilPapers and EthxWeb databases, restricted to peer-reviewed journal publications in English. Papers containing ethical reasons were analyzed, and the reasons were coded according to whether they were endorsed, mentioned or rejected. RESULTS: Four hundred thirty-one articles were retrieved by our search, and 88 were ultimately included and analyzed. Within these articles, we found 464 passages containing reasons for and against conducting human-animal chimera research. We classified these reasons into five categories and, within these, identified 12 broad and 31 narrow reason types. 15% of the retrieved passages contained reasons in favor of conducting chimera research (Category P), while 85% of the passages contained reasons against it. The reasons against conducting chimera research fell into four further categories: reasons concerning the creation of a chimera (Category A), its treatment (Category B), reasons referring to metaphysical or social issues resulting from its existence (Category C) and to potential downstream effects of chimera research (Category D). A significant proportion of identified passages (46%) fell under Category C. CONCLUSIONS: We hope that our results, in revealing the conceptual and argumentative structure of the debate and highlighting some its most notable tendencies and prominent positions, will facilitate continued discussion and provide a basis for the development of relevant policy and legislation.

The Emergence and Development of Animal Research Ethics: A Review with a Focus on Nonhuman Primates.

The ethics of using nonhuman animals in biomedical research is usually seen as a subfield of animal ethics. In recent years, however, the ethics of animal research has increasingly become a subfield within research ethics under the term "animal research ethics". Consequently, ethical issues have become prominent that are familiar in the context of human research ethics, such as autonomy or self-determination, harms and benefits, justice, and vulnerability. After a brief overview of the development of the field and a discussion of relevant theoretical ethical frameworks, I consider two of these issues, namely autonomy and self-determination on the one hand, and harms and benefits on the other hand. My concern is with philosophical and ethical issues, rather than animal research oversight. I focus my discussion on nonhuman primates, as the most plausible nonhuman candidates for this approach. I conclude that the approach, although promising, depends strongly on the moral status of nonhuman research subjects.

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.

Ethical Considerations in Animal Research: The Principle of 3R's.

In the last century, progress in the knowledge of human diseases, their diagnosis and treatment have grown exponentially, due in large part to the introduction and use of laboratory animals. Along with this important progress, the need to provide training and guidance to the scientific community in all aspects related to the proper use of experimental animals has been indispensable. Animal research committees play a primary role in evaluating experimental research protocols, from their feasibility to the rational use of animals, but above all in seeking animal welfare. The Institutional Committee for the Care and Use of Animals (IACUC) has endeavored to share several relevant aspects in conducting research with laboratory animals. Here, we present and discuss the topics that we consider of utmost importance to take in the account during the design of any experimental research protocol, so we invite researchers, technicians, and undergraduate and graduate students to dive into the fascinating subject of proper animal care and use for experimentation. The main intention of these contributions is to sensitize users of laboratory animals for the proper and rational use of them in experimental research, as well as to disseminate the permitted and unpermitted procedures in laboratory animals. In the first part, the significance of experimental research, the main functions of IACUC, and the principle of the three R's (replacement, reduction, and refinement) are addressed.

Legal aspects of zebrafish neuropharmacology and neurotoxicology research.

Despite the growing emphasis on translational neuropharmacology and drug discovery research, the legality underlying these fields are seldom considered. The zebrafish (Danio rerio) is an increasingly utilized model organism in neuropharmacology and neurotoxicology. As the acceptance of zebrafish in biomedicine continues to grow, the legal aspects of their applications remain outpaced by this exponential growth. Therefore, there is a need to evaluate the legal aspects of zebrafish applications to CNS drug research. Here, we discuss a wide range of regulatory topics relevant to zebrafish research, such as the bioethics of experimentation (including studies of stress and pain), welfare protection laws, the recent advances in CNS drug discovery, and specific legal aspects of controlled substance research in this aquatic species. The conceptualization and understanding of the zebrafish welfare and its promise as a model in toxicology can also potentially shape environmental protection practices and inform policy making.

A framework for the ethical assessment of chimeric animal research involving human neural tissue.

BACKGROUND: Animal models of human diseases are often used in biomedical research in place of human subjects. However, results obtained by animal models may fail to hold true for humans. One way of addressing this problem is to make animal models more similar to humans by placing human tissue into animal models, rendering them chimeric. Since technical and ethical limitations make neurological disorders difficult to study in humans, chimeric models with human neural tissue could help advance our understanding of neuropathophysiology. MAIN BODY: In this article, we examine whether the introduction of human neural tissue and any consequent cognitive change is relevant to the way we ought to treat chimeras. We argue that changes in cognitive abilities are morally relevant to the extent that they increase the capacities that affect the moral status of any entity, including awareness, autonomy, and sociability. We posit that no being, regardless of species, should be treated in a way that is incommensurate with its moral status. Finally, we propose a framework that can be used to guide ethical assessment of research involving chimeras with advanced cognitive capacities. CONCLUSION: We advance this framework as a useful tool for bringing relevant considerations to the forefront for those considering the ethical merit of proposed chimeric research. In doing so, we examine concepts relevant to the question of how any entity may be treated, including moral status, dignity, and capacities.