Ethical Animal Research Research Articles

Donald Griffin, sentience, and animal research ethics

Donald Griffin, sentience, and animal research ethics

Interdisciplinary Animal Research Ethics-Challenges, Opportunities, and Perspectives.

Can nonhuman animals be used for the benefit of humans in a scientifically and morally justified manner and, if yes, how? Based on our own experiences as scholars from various academic backgrounds, we argue that this question can only be answered as an interdisciplinary and international endeavor, considering insights from research ethics and animal ethics as well as scientific and legal aspects. The aim of this article is to contribute to the foundation of the emerging field of animal research ethics. In doing so, we describe the following seven phases of animal research experiments: ethical, legal and social presumptions (phase 0), planning (phase I), review (phase II), conduct of experiments (phase III), publication/dissemination (phase IV), further exploitation of results (phase V), and evaluation (phase VI). In total, 20 key ethical, legal, and practical challenges that an ethical framework for the use of animals in research needs to address are identified and analyzed. Finally, we characterize the following four meta-challenges and opportunities associated with animal research ethics as a field: (1) moral pluralism, (2) the integration of views and positions outside the laboratory, (3) international plurality of conduct, standards, and legal norms, and (4) interdisciplinary education.

Study design: think 'scientific value' not 'p-values'.

Statistically based experimental designs have been available for over a century. However, many preclinical researchers are completely unaware of these methods, and the success of experiments is usually equated only with 'p < 0.05'. By contrast, a well-thought-out experimental design strategy provides data with evidentiary and scientific value. A value-based strategy requires implementation of statistical design principles coupled with basic project management techniques. This article outlines the three phases of a value-based design strategy: proper framing of the research question, statistically based operationalisation through careful selection and structuring of appropriate inputs, and incorporation of methods that minimise bias and process variation. Appropriate study design increases study validity and the evidentiary strength of the results, reduces animal numbers, and reduces waste from noninformative experiments. Statistically based experimental design is thus a key component of the 'Reduction' pillar of the 3R (Replacement, Reduction, Refinement) principles for ethical animal research.

34 The influence and interaction of nutrition with the immune system in companion animal models

Abstract Understanding the impacts of nutrients in a species-specific manner has both practical and academic benefits for improving animal health. Therefore, species-specific animal models and research reagents are crucial to understanding molecular and physiological pathways. However, limitations in repeatable, descriptive models, sample size, and the ethics of companion animal research result in often needing to make inferences from human, murine, and other related immunology and nutrition research models. Recent companion animal work has focused on the impact of key nutrients in animal diets, including fat-soluble vitamins D, and E, omega-3 polyunsaturated fatty acids (PUFA), overall amino acid and energy balance over the lifespan, minerals including zinc and selenium, and feed additives such as probiotics and beta glucans. The selected research model, samples able to be collected, and available reagents for sample analysis will impact potential outcomes and inferences made from the data, including both acute to chronic impacts. From a theoretical standpoint, the balance between nutrient supplementation and impact includes understanding nutrients and responses of a model system in both deficiency and therapeutic level settings. For example, when supplementing Vitamin D, Vitamin E, or omega-3 polyunsaturated fatty acids, inclusion above currently recommended levels may optimize immune function, such as pathogen clearance, improved vaccine titer responses, or reduce inflammation. For other nutrients associated with immunomodulation such as zinc, additional chronic pharmacological supplementation may inhibit certain aspects of immune function, much like a deficiency scenario. Overstimulation of the immune system through nutrient supplementation may also impact the necessary modulation and repair roles that immune cells such as macrophages play in wound healing and anti-inflammatory responses. Continued work in nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in companion animals.

Circadian variations influence anxiety-related behaviour, olfaction, and hedonic response in male Sprague–Dawley rats

IntroductionDespite the acknowledged impact of circadian rhythms on various aspects of life, behavioural tests with laboratory animals often overlook alignment with their natural activity patterns. This study aims to evaluate the influence of circadian variations on the results, validity, and reliability of different behavioural tests in rats. MethodsThree behavioural tests, the Light-Dark Box Test (LDB), assessing anxiety-related behaviour and locomotor activity; the Buried Pellet Test (BPT), revealing olfactory abilities and motivation issues; and the Sucrose Preference Test (SPT), studying the anhedonic response, were employed to encompass multiple daytime-dependent behavioural aspects in male Sprague-Dawley rats. ResultsOur findings underscore distinct circadian effects on locomotor activity, exploratory behaviour, olfactory acuity, motivation, and hedonic response. Notably, anxious behaviour remained unaffected by daytime conditions. Furthermore, decreased data variance was found to be correlated with conducting behavioural tests during the subjects’ active phase. DiscussionThis study demonstrates extensive circadian influences on nearly all parameters investigated, coupled with a significant reduction in data variability during the active phase. Emphasising the importance of aligning experimental timing with rats’ natural activity patterns, our results suggest that conducting tests during the active phase of the animals not only refines test sensitivity , reduces stress, and provides more representative data, but also contributes to ethical animal research (3 R) and improves test relevance. This, in turn, enhances the reliability and validity of experimental outcomes in behavioural research and promotes animal welfare.

Ex Vivo Porcine Experimental Model for Studying and Teaching Lung Mechanics.

Mechanical ventilation is widely used and requires specific knowledge for understanding and management. Health professionals in this field may feel insecure and lack knowledge because of inadequate training and teaching methods. Therefore, the objective of this article is to outline the steps involved in generating an ex vivo porcine lung model to be used in the future, to study and teach lung mechanics. To generate the model, five porcine lungs were carefully removed from the thorax following the guidelines of the Animal Research Ethics Committee with adequate care and were connected to the mechanical ventilator through a tracheal cannula. These lungs were then subjected to the alveolar recruitment maneuver. Respiratory mechanics parameters were recorded, and video cameras were used to obtain videos of the lungs during this process. This process was repeated for five consecutive days. When not used, the lungs were kept refrigerated. The model showed different lung mechanics after the alveolar recruitment maneuver every day; not being influenced by the days, only by the maneuver. Therefore, we conclude that the ex vivo lung model can provide a better understanding of lung mechanics and its effects, and even of the alveolar recruitment maneuver through visual feedback during all stages of the process.

Human Brain Organoid Transplantation: Testing the Foundations of Animal Research Ethics

Alongside in vitro studies, researchers are increasingly exploring the transplantation of human brain organoids (HBOs) into non-human animals to study brain development, disease, and repair. This paper focuses on ethical issues raised by such transplantation studies. In particular, it investigates the possibility that they might yield enhanced brain function in recipient animals (especially non-human primates), thereby fundamentally altering their moral status. I assess the critique, raised by major voices in the bioethics and science communities, according to which such concerns are premature and misleading. I identify the assumptions underlying this skeptical critique, and mention some objections against them, followed by some possible replies. I proceed to argue that the skeptical position is ultimately implausible, because it presupposes an unreasonably high standard of full moral status. My argument appeals to David DeGrazia’s idea of a “borderline person”, and to the need for consistency with existing animal research regulations. I outline the practical implications of my view for the conduct of studies that might result in the development of full moral status in a transplanted animal. I also discuss some of the ethical implications of animal enhancement (particularly of rodents) below the threshold associated with full moral status. I conclude that far from being premature, further debate on these issues is urgently needed to help clarify the prospects that a neural chimera might attain full moral status in the foreseeable future, and the level of quality of life required to make it acceptable to knowingly create such a being via HBO transplantation.

Animal rights, animal research, and the need to reimagine science

What would it look like for researchers to take non-human animal rights seriously? Recent discussions foster the impression that scientific practice needs to be reformed to make animal research ethical: just as there is ethically rigorous human research, so there can be ethically rigorous animal research. We argue that practically little existing animal research would be ethical and that ethical animal research is not scalable. Since animal research is integral to the existing scientific paradigm, taking animal rights seriously requires a radical, wholesale reimagining of science. Trial registration: ClinicalTrials.gov identifier: NCT05340426.

Critical key points for anesthesia in experimental research involving sheep (Ovis aries)

Anesthesia and analgesia have a major impact on ensuring animal welfare and safety, resulting in reduced stress response and effective pain control, ensuring the comfort of the animal, promoting faster recovery, and reducing the risk of complications associated with various research procedures. Each stage of anesthesia in sheep is vital for maintaining the animal's welfare, ensuring procedural success, minimizing stress, risks, and complications, and optimizing the quality of research data. Proper attention to detail and adherence to best practices at each stage contribute to the overall success of anesthesia management in sheep. Anesthesia protocols should suit individual requirements for each sheep, in light of factors such as health status, procedure duration, and desired anesthesia depth. Meticulous monitoring, adherence to best practices, and prompt intervention are essential for minimizing the risks of complications during sheep anesthesia and ensuring the safety and welfare of the animals undergoing anesthesia for research purposes. This article presents the main key points that can improve anesthetic management for sheep involved in experimental research to minimize stress response and complications, enhancing animal safety, welfare, and comfort during and after procedures. Multimodal anesthesia approaches ensure effective pain relief, tailored to the specific needs of individual animals or procedures, optimizing outcomes and minimizing risks. Anesthesia management contributes to improved research data collection under conditions that enhance the validity and reliability of results. Sheep's impressive capacity to maintain homeostasis even during extended periods of anesthesia highlights the critical importance of upholding data quality in alignment with the universally accepted principles of Replacement, Reduction, and Refinement for ethical animal research. By adhering to these principles, researchers can minimize the number of animals used, reduce any potential discomfort or distress experienced by the animals, and refine procedures to optimize animal welfare while still achieving scientific objectives.

Unveiling the Landscape of Animal Research Ethics among Saudi Health College Students

Unveiling the Landscape of Animal Research Ethics among Saudi Health College Students

Conscience of Science: Ethical Imperatives in Zoological Research

Zoological science is an intricate field which requires intimate considerations and guidelines to make sure that limits and boundaries are set for the ethical and humane conduction of research. A number of bioethical laws and international conventions have been designed by bioethical and committees and review boards that serve as moral compass steering towards responsible and humane scientific research. Animal Welfare Act (AWA) sets standards for the responsible treatment of animals in research, transport, exhibition and animal dealers, handling and research protocols, Guide for the Care and Use of Laboratory Animals that is published by National research Council of Unites States provides a framework for the proper use and optimal care of animals for in vivo research in laboratory experiments [1]. Similarly, European Union Directive 2010/63/EU is a directive which outlines the standards for the animal protection used for research purposes in the Europe. It states 3Rs of animal testing i.e., Refinement, Reduction and Replacement, and necessitates that researchers consider alternatives before resorting to the animal experiments. An elaborate directive, Declaration of Helsinki, primarily focuses on human research ethics but has principle related o animal research ethics as well [2]. Likewise, another Convention on International Trade in Endangered Species of Wild Fauna and Flora also called as CITES, deals with the trade of endangered animals ensuring that any research which involves endangered species is conducted ethically with proper permits and prevents illegal and unethical exploitation of animals [3]. Last but not the least, the ARRIVE guidelines provide a checklist of essential information which must be included while publishing the research data which describes animal experiments, promotes transparency and improve the quality of reporting in the animal research. The current global conditions necessitate ethical consciousness in zoological research. These considerations extend beyond laboratory settings and encompass wildlife conservation and the prevention of zoonotic diseases such as COVID-19. Innovations in non-invasive research methods, genetic analyses, and data-driven insights pave the way for more ethical and efficient scientific practices. Ethical consciousness aligning with the pursuit of knowledge nurtures a landscape where wonder of discovery and the ethical treatment of animals walk hand in hand.

Who reviews what you do at the zoo? Considerations for research ethics with captive exotic animals

Research in zoos is an important scientific endeavor that requires several complex considerations in order to occur. Among those many considerations are the ethics involved in conducting zoo research. However, it is not always clear how zoo researchers should go about resolving any research ethics matters, even determining when some type of research ethics committee should be involved in those deliberations. Our paper attempts to provide some resolutions for these issues, namely in three sections: (1) a brief history of human and animal research ethics, (2) general guidelines for zoo research ethics applications, and (3) theoretical, ethical dilemmas at the zoo. In each section, we consider pragmatic attempts to resolve any issues, as well as provide examples to illustrate our points. The primary focus of the paper is to facilitate consideration of the wide array of ethical factors any zoo researcher might encounter, as well as provide a basic set of ethical guidelines for zoo research. We also emphasize the importance of the welfare of the animals for all zoo research projects.

When Is Something an Alternative? A General Account Applied to Animal-Free Alternatives to Animal Research.

The first "R" from animal research ethics prescribes the replacement of animal experiments with animal-free alternatives. However, the question of when an animal-free method qualifies as an alternative to animal experiments remains unresolved.Drawing lessons from another debate in which the word "alternative" is central, the ethical debate on alternatives to germline genome editing, this paper develops a general account of when something qualifies as an alternative to something. It proposes three ethically significant conditions that technique, method, or approach X must meet to qualify as an alternative to Y: (1) X must address the same problem as Y, under an appropriate description of that problem; (2) X must have a reasonable chance of success, compared to Y, in solving the problem; and (3) X must not be ethically unacceptable as a solution. If X meets all these conditions, its relative advantages and disadvantages determine whether it is preferable, indifferent, or dispreferable as an alternative to Y.This account is then applied to the question of whether animal-free research methods qualify as alternatives to animal research. Doing so breaks down the debate around this question into more focused (ethical and other) issues and illustrates the potential of the account.

Caenorhabditis elegans for research on cancer hallmarks.

After decades of research, our knowledge of the complexity of cancer mechanisms, elegantly summarized as 'hallmarks of cancer', is expanding, as are the therapeutic opportunities that this knowledge brings. However, cancer still needs intense research to diminish its tremendous impact. In this context, the use of simple model organisms such as Caenorhabditis elegans, in which the genetics of the apoptotic pathway was discovered, can facilitate the investigation of several cancer hallmarks. Amenable for genetic and drug screens, convenient for fast and efficient genome editing, and aligned with the 3Rs ('Replacement, Reduction and Refinement') principles for ethical animal research, C. elegans plays a significant role in unravelling the intricate network of cancer mechanisms and presents a promising option in clinical diagnosis and drug discovery.

Increasing information gain in animal research by improving statistical model accuracy

Reduction of the numbers of laboratory animals is one of the three pillars of ethical animal research. Equivalently, information gain per animal should be maximized. A road towards this goal that is barely taken in current animal research is the more accurate statistical modeling of experiments. Here we show for a typical experiment (“open field test”) with outcomes that are non-normally distributed count data, how this can be implemented and what information gain is achieved. We contrast the state of the art – the use of confidence intervals based on null-hypothesis significance testing (NHST) –, with a Bayesian approach with the same underlying normal model, and a Bayesian approach with a more accurate negative binomial model. We find that the more accurate model leads to a marked improvement of knowledge gained with the experiment, especially for small sample sizes. As experimental data that violate assumptions of simple, conventional models are frequent, our findings have wider implications.

The 12 Rs Framework as a Comprehensive, Unifying Construct for Principles Guiding Animal Research Ethics

Animal research ethics and animal welfare in science have become progressively tightly regulated, and ethical integrity and scientific quality, as well as social responsiveness and responsibility have become key requirements for research to be approved, funded, published, and accepted. The multitude of factors to contemplate has in some instances not only become complex, requiring a team approach, but often perceived as confusing and overwhelming. To facilitate a process of simplistic yet comprehensive conceptualization, we developed the 12 Rs Framework to act as a mind map to guide scientists, oversight structures, and other stakeholders through the myriad of ethical considerations. It unfolds into three domains of twelve encompassing ethical principles, values, and other considerations, including the animal welfare, social values, and scientific integrity domains, whilst also recognizing the diversity of local context, legal requirements, values, and cultures around the globe. In the end, it can be seen as a unifying ethical framework to foster and promote animal research ethics.

Differential Angiogenic Induction Impacts Nasal Polyp Tissue Growth.

In chronic rhinosinusitis with nasal polyps, inflammatory edema drives tissue remodeling favoring anomalous growth of the nasal mucosa, but a proangiogenic contribution of nasal polyp in support of tissue growth is still controversial. The chorioallantoic membrane of chicken embryo model was employed to address the potentiality of nasal tissue fragments to modulate angiogenesis. Fifty-seven fertilized eggs were implanted with polyp or healthy nasal mucosa tissue or were kept as non-implanted controls. The embryos' size, length, and development stage, and chorioallantoic membrane vasculature morphology were evaluated after 48h. Quantitative computer vision techniques applied to digital chorioallantoic membrane images automatically calculated the branching index as the ratio between the areas of the convex polygon surrounding the vascular tree and the vessels' area. Ethics approval and consent to participate: the study was approved by the Human Research Ethics Committee of the Federal University of São Paulo (CAAE number: 80763117.1.0000.5505) and by the Animal Research Ethics Committee of University of São Paulo (nº CEUA 602-2019). Mucosal, but not polyp tissue implants, hampered embryo development and induced underdeveloped chorioallantoic membranes with anastomosed, interrupted, and regressive vessels. Vessels' areas and branching indexes were higher among the chorioallantoic membranes with polyp implants and controls than among those with healthy mucosa implants. Nasal polyp presents differential angiogenic induction that impacts tissue growth.

Comparison of in vitro Maturation Media on Cattle Oocytes after in vitro Embryo Production

The study was conducted to compare differences in vitro maturation media and their effect on subsequent in vitro embryo production. The study procedures were approved by the agricultural research council animal ethics committee (Ref no: APAEC 2020/05) and the Tshwane university of technology animal research ethics committee (Ref no: AREC 2021/08/004). Follicular fluid containing a suspension of oocytes was retrieved from ovaries through aspiration and slicing techniques. The retrieved oocytes were graded and randomly matured into four media (TCM199, Vitromat Protect, and BO IVM®) groups for 22 h, evaluated for polar body extrusion, fertilized through their respective in vitro fertilization media, and evaluated for pronucleus status. Presumptive zygotes were further cultured in vitro in their respective media, incubated for either 18 or 96 h, and evaluated for cleavage rates. The data was subjected to an appropriate analysis of variance. Student's Least Significant Differences (t-LSD) was calculated at a 5% significance level to compare means of significant treatment effects. The BO-IVM® (57.4%), TCM 199 (55.6%), and VitroMat Protect® (54.0%) recorded higher results than EGF (26.9%) for polar body formation on oocytes (P<0.05). Vitrofert® medium recorded a higher percentage (43.3%) of total fertilization rate when compared to the other media (P<0.05). VitroCleave Plus® medium recorded a higher total cleavage rate (43.3%) as compared to the other media (P<0.05). In conclusion, TCM 199, BO-IVM®, and VitroMat Protect® media rendered higher results of oocyte polar body extrusion rates compared to the EGF medium. Vitrofert® medium recorded a higher percentage (43.3%) of total fertilization rate when compared to the other media. Higher embryo development (4-8 cells and total cleavage) rates were observed in VitroCleave Plus® medium. Overall, the introduced media (VitroMat Protect®) and its media suite successfully adapted to the laboratory environment in South Africa (SA) and can therefore be adopted for optimizing the in vitro Embryo Production (IVEP) of cattle oocytes.

Sustainable education and training in laboratory animal science and ethics in low- and middle-income countries in Africa - challenges, successes, and the way forward.

Despite the recognised need for education and training in laboratory animal science (LAS) and ethics in Africa, access to such opportunities has historically been limited. To address this, the Pan-African Network for Laboratory Animal Science and Ethics (PAN-LASE) was established to pioneer a support network for the development of education and training in LAS and ethics across the African continent.In the 4.5 years since the establishment of PAN-LASE, 3635 individuals from 28 African countries have participated in our educational activities. Returning to their home institutions, they have both established and strengthened institutional and regional hubs of knowledge and competence across the continent. Additionally, PAN-LASE supported the development of guidelines for establishment of institutional Animal Ethics Committees, a critical step in the implementation of ethical review processes across the continent, and in enhancing animal welfare and scientific research standards.Key challenges and opportunities for PAN-LASE going forward include the formalisation of the network; the sustainability of education and training programmes; implementation of effective hub-and-spoke models of educational provision; strengthening governance frameworks at institutional, national and regional levels; and the availability of Africa-centric open access educational resources.Our activities are enhancing animal welfare and the quality of animal research undertaken across Africa, enabling African researchers to undertake world-leading research to offer solutions to the challenges facing the continent. The challenges, successes and the lessons learnt from PAN-LASE's journey are applicable to other low- and middle-income countries across the world seeking to enhance animal welfare, research ethics and ethical review in their own country or region.

NEED, SCOPE AND LIMITATIONS OF ANIMAL STUDY IN PERSPECTIVE OF AYURVEDA: A REVIEW

Ayurveda is a goldmine for researchers. Unfortunately, very few researches are planned with a comprehensive approach. Animals have been used repeatedly throughout the history of biomedical research analysis. The utilization of non-human animals in biomedical research has made an essential contribution from precedent days. These animal experiments advance understanding of anatomy, physiology, pathology, pharmacology, and various medical fields. However, natural laboratory-based new research is still awaited. Our objective was to compile the most recent data on animal study's needs, scope and limitations. Also, we tend to overlook how we conduct a department-wise animal study, the ethics of the animal study, and the similarities between animals and man and their unique mechanisms. We conduct a narrative review. There is a need and scope for animal study in medical bioscience because a cure for a disease proves the safety and efficacy of new treatments attained through animal testing. There are also some limitations in animal studies, like loss of biological variability or predictivity from the utilization of inbred strains, young animals, restriction to single sexes, and inadequate cluster sizes. Also, there are so many department-wise uses and limitations of animal study. Conclusion: Animal study proves beneficial for the future because animals are often used in medical research to investigate the progression of the disease, test new drugs, surgeries, etc. But before that, we must always study the ethics of animal research to avoid unskilled, pseudoscientific and needlessly repetitive studies that bring on reserve damage to laboratory animals.