Establishing a culture of care, conscience, and responsibility: addressing the improvement of scientific discovery and animal welfare through science-based performance standards

Science-based performance standards offer a viable means of reducing regulatory burden while ensuring that research animal welfare and high-quality research data are realized. Unlike rigid regulations, science-based performance standards evolve as new information becomes available, thereby allowing new discoveries to be implemented in a timely manner and in a way that more effectively benefits the animals and the science. The implementation of performance standards requires a well-coordinated institutional team composed of the administration, research staff, the institutional animal care and use committee, professional and technical animal care personnel, occupational health and safety staff, and physical plant staff. This animal program team is best supported in an institutional environment that reflects a culture of care, compliance, and responsibility. In such a culture, the professional judgment exercised by the team is well grounded in meeting the diverse needs of the program's customers, who include the animals, the researchers, and research stakeholders such as the public. The institutional culture of care, compliance, and responsibility fosters workplace integrity, an ethics-based decision-making paradigm, sound understanding of institutional expectations through good communication and clear lines of authority, the hiring and retention of trained and well-qualified individuals, and a system for continuous development and improvement of the program.     

A step-by-step guide to systematically identify all relevant animal studies

Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future.     

An hourly variation in zoo visitor interest: measurement and significance for animal welfare research

A methodological difficulty facing welfare research on nonhuman animals in the zoo is the large number of uncontrolled variables due to variation within and between study sites. Zoo visitors act as uncontrolled variables, with number, density, size, and behavior constantly changing. This is worrisome because previous research linked visitor variables to animal behavioral changes indicative of stress. There are implications for research design: Studies not accounting for visitors' effect on animal welfare risk confounding (visitor) variables distorting their findings. Zoos need methods to measure and minimize effects of visitor behavior and to ensure that there are no hidden variables in research models. This article identifies a previously unreported variable—hourly variation (decrease) in visitor interest—that may impinge on animal welfare and validates a methodology for measuring it. That visitor interest wanes across the course of the day has important implications for animal welfare management; visitor effects on animal welfare are likely to occur, or intensify, during the morning or in earlier visits when visitor interest is greatest. This article discusses this issue and possible solutions to reduce visitor effects on animal well-being.     

湖南省2006～2010年实验动物微生物质量监测结果分析

目的了解湖南省实验动物微生物学质量,为实验动物实行科学管理提供重要依据,保证实验动物质量,确保实验结果准确和实验动物科技事业工作者的职业健康与安全。方法在相关单位生产繁殖群以单纯随机抽样原则采样,按照GB 14922.2-2001、GB/T 14926-2001和GB/T14926.21-2008进行实验动物微生物检测。结果 SPF级大鼠批次合格率为73.68%,SPF级小鼠批次合格率为77.78%,普通级新西兰兔批次合格率为60.61%,普通级豚鼠批次合格率为100%。结论我省2006～2010年实验动物微生物学质量前期呈现下降趋势,后期得到较大改善。要继续采取措施加强实验动物管理,消除实验动物种群微生物感染。     

Use of factorial designs to optimize animal experiments and reduce animal use

Optimization of experiments, such as those used in drug discovery, can lead to useful savings of scientific resources. Factors such as sex, strain, and age of the animals and protocol-specific factors such as timing and methods of administering treatments can have an important influence on the response of animals to experimental treatments. Factorial experimental designs can be used to explore which factors and what levels of these factors will maximize the difference between a vehicle control and a known positive control treatment. This information can then be used to design more efficient experiments, either by reducing the numbers of animals used or by increasing the sensitivity so that smaller biological effects can be detected. A factorial experimental design approach is more effective and efficient than the older approach of varying one factor at a time. Two examples of real factorial experiments reveal how using this approach can potentially lead to a reduction in animal use and savings in financial and scientific resources without loss of scientific validity.     

Experimental animal urine collection: a review

Animal urine collection is a vital part of veterinary practice for ascertaining animal health and in scientific investigations for assessing the results of experimental manipulations. Untainted animal urine collection is very challenging, especially with small rodents, and is an almost impossible task under conditions of microgravity. The fundamental aspects of urine collection are: (1) ease of collection, (2) quality of sample, (3) prevention of contamination, (4) severity of procedures used, (5) levels of pain caused to the animal and (6) refinement of methods to reduce stress, pain or distress. This review addresses the collection of urine for qualitative and quantitative purposes from rodents, rabbits, felines, canines, avian species, equines, porcines, ungulates and certain non-human primates, with animal welfare in mind. Special emphasis has been given to rodents, canines and non-human primates, since they are the animals of choice for research purposes. Free catch (voluntary voiding), methods with mild intervention, surgical methods, modified restraint, cage and special requirement methods have been reviewed here. Efforts need to be taken to provide appropriate animal husbandry and to nurture the animals in as natural an environment as possible since experimental results obtained from these research subjects are, to a great extent, dependent upon their well-being. A continuous refinement in the procedures for collecting urine from experimental animals will be the most efficient way of proceeding in obtaining pure urine specimens for obtaining reliable research data.     

Institutional and IACUC responsibilities for animal care and use education and training programs

Training and instruction of personnel are important components of animal care and use programs because they help to ensure the health and welfare of the animals and the integrity of the research or testing results. Training also helps to promote the consideration of alternatives, recognition of animal pain and distress, appropriate use of pain-relieving agents, aseptic technique, pre- and post-procedural care, and personnel health and safety. While individuals who provide the care for or conduct research or testing in laboratory animals should take personal responsibility for ensuring that they have the skills to perform their duties, the institution is ultimately responsible for ensuring their competency. The institution is also responsible for providing the training or instruction that is required by federal legislation, regulations, and policies. The institutional animal care and use committee (IACUC) is responsible for ensuring, as part of their review of research activities, that the personnel are capable of performing the procedures described. The IACUC must also assess the institution's training program as part of their semiannual animal care and use program review and make recommendations regarding training to the institutional official. This article provides a comprehensive overview of the US regulatory mandates for training and personnel qualification.     

Reduction through education: the insight of a trainer

One of the articles contained within European Council Directive 86/609/EEC states that "Persons who carry out experiments or take part in them, and persons who take care of animals used for experiments, including duties of a supervisory nature, shall have appropriate training". In effect, this article stipulates that only competent individuals are allowed to work with laboratory animals. At least three groups of individuals can be identified with different responsibilities toward experimental animals: animal technicians, scientists, and veterinarians/animal welfare officers. The responsibilities and duties of the individuals within each of these categories differ. This paper focuses on the training of scientists. The scientist designs, and often also performs, animal experiments. Therefore, scientists must be educated to develop an attitude of respect toward laboratory animals, and must be trained so that, if an experiment must be performed with animals, it is designed according to the highest possible scientific and ethical standards. In The Netherlands, the law stipulates that scientists intending to work with animals must have completed a course in laboratory animal science. This compulsory course started in 1986. The Department of Laboratory Animal Science at Utrecht University is responsible for the national coordination of this course. Participants must have an academic degree (at the level of MSc) in one of the biomedical sciences, such as biology, medicine or veterinary medicine. Although the course is an intensive 3-week, 120-hour long course, which covers both technical and ethical aspects of laboratory animal experimentation, it cannot provide full competence. It is designed to provide sufficient basic training and knowledge to enable students to design animal experiments, and to develop an attitude that will be conducive to the implementation of the Three Rs. However, full competence will always require further training that can only be acquired as a result of practical experience gained while working in the field of laboratory animal research. Evaluations subsequent to the course have revealed that more than 98% of the students regard the course as indispensable for all scientists working in a research area where animal experiments are performed. They agree that the course not only contributes to the quality of experiments and to the welfare of animals, but also to a decrease in the number of animals used in experiments.     

Issues related to the use of animals in biocontainment research facilities

The expansion and improvement of high-containment animal facilities has been driven by terrorism, economics, the emergence of new pathogens, and the re-emergence of other pathogens in new areas. Working with highly infectious viral agents requires a team of trained scientists, laboratory technicians, veterinarians, animal care staff, biological safety officers, engineers, and physical plant staff to ensure safety, biocontainment, and the animals' well being, while providing essential scientific data. The challenges of working with infectious disease agents in high levels of containment, and some solutions to these challenges, are described from an animal care point of view.     

A sample postapproval monitoring program in academia

The primary goal of an animal care and use program (ACUP) should be to ensure animal well-being while fostering progressive science. Both the Animal Welfare Act (and associated regulations) and the Public Health Service (PHS) Policy require the institutional animal care and use committee (IACUC) to provide oversight of the animal program through continuing reviews to ensure that procedures are performed as approved by the committee. But for many committees the semiannual assessment does not provide an opportunity to observe research procedures being performed. Furthermore, IACUC members are typically volunteers with other full-time commitments and may not be able to dedicate sufficient time to observe protocol performance. Postapproval monitoring (PAM) is a tool that the IACUC can use to ensure that the institution fulfills its regulatory obligation for animal program oversight. When performed by attentive and observant individuals, PAM can extend the IACUC's oversight, management, training, and communication resources, regardless of program size or complexity. No defined PAM process fits all institutions or all situations; rather, the monitoring must match the program under review. Nonetheless, certain concepts, concerns, and conditions affect all PAM processes; they are described in this article. Regardless of the style or depth of PAM chosen for a given program, one thing is sure: failure of the IACUC to engage all available and effective oversight methods to ensure humane, compassionate, efficient, and progressive animal care and use is a disservice to the institution, to the research community and to the animals used for biomedical research, testing, or teaching.     

Survey of the Quality of Experimental Design,Statistical Analysis and Reporting of Research Using Animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria.     

The scope for improving the design of laboratory animal experiments.

The factors which need to be taken into account in designing a 'good' experiment are reviewed. Such an experiment should be unbiased, have high precision, a wide range of applicability, it should be simple, and there should be a means of quantifying uncertainty (Cox 1958). The relative precision due to the use of randomized block designs was found to range from 96% to 543% in 5 experiments involving 30 variables. However, a survey of 78 papers published in two toxicology journals showed that such designs were hardly used. Similarly, designs in which more than one factor was varied simultaneously ('factorial designs') were only used in 9% of studies, though interactions between variables such as dose and strain of animal may be common, so that single factor experiments could be misleading. The consequences of increased within-group variability due to infection and genetic segregation were quantified using data published by G?rtner (1990). Both substantially reduced precision, but toxicologists continue to use non-isogenic laboratory animals, leading to experiments with a lower level of precision than is necessary. It is concluded that there is scope for improving the design of animal experiments, which could lead to a reduction in animal use. People using animals should be required to take formal training courses which include sessions on experimental design in order to minimize animal use and to increase experimental efficiency.     

Ethical issues concerning animal research outside the laboratory

Unique ethical issues can be associated with research outside the customary laboratory setting. Protocols involving wild animals must consider that any infringement on the wild nature of the species can be disruptive and may involve pain, fear, anxiety, and frustration, all of which constitute ethical harm that must be balanced with anticipated benefit. Agricultural and companion animal research, however, take place in a human-engineered environment and involves domesticated species adapted to human contact. Special animal welfare issues can be related to agricultural production goals that fail to deal adequately with moral concerns. Human/companion animal relationships, on the other hand, present unique moral obligations to animal owners. Other factors may present additional ethical issues when research is performed outside the laboratory. These factors include a required sensitivity to the environment of wild animals and an awareness that this outside research may to quite public and, therefore, vulnerable to community perception. The institutional animal care and use committee(IACUC) has the responsibility to ensure that research in outside settings is ethical and properly implemented. This responsibility requires that IACUC members have knowledge of the needs of a wide range of species and that a process is in place to allow effective monitoring of research in remote locations. Finally, and most important, there must be a sensitivity to the unique ethical considerations outlined here. Armed with these strengths, the IACUC will be effective in what may be unfamiliar surroundings and will have a significant opportunity to cause improvements in animal welfare.     

The refining influence of ethics committees on animal experimentation in Sweden

Mandatory scrutiny of projects by animal ethics committees was introduced in Sweden in 1979. The present study investigated the minutes of meetings held between 1989 and 2000 at which consideration of applications for experimental work in animals resulted in requests for modification (n = 3607). 18.1% of the applications received were approved only after modifications. The majority of the changes requested may be classified as 'Refinement'. The most common requests were for improvement of project design, euthanasia method and housing and husbandry. There was a relative increase in modifications requested by the committees related to anaesthesia, choice of licensed supervisor and the need for licenses or informed consent from animal owners during the period investigated. There was a relative decrease in modifications related to euthanasia, housing and husbandry, and general endpoint assertions. The results suggest that the work of the committees may be perceived as an ongoing process, since several of the applications for which modification was requested were projects that had been approved on a previous occasion but were now up for renewal. In order to have maximal influence on the refinement of scientific protocols it is important that the scientists in the committees are continuously updated on developments in laboratory animal science.     

Avoiding an overzealous approach: a perspective on regulatory burden

The authors discuss the impact of regulatory burden on the research enterprise, with emphasis on animal care and use programs. They identify three sources of regulatory burden: specific requirements in law and regulation, interpretive requirements or "guidance" by regulatory agencies, and self-imposed regulatory burden resulting from institutional interpretations. Attempting to minimize the risks of noncompliance through the overzealous application of "requirements" does not necessarily benefit the animals. Balancing risks associated with animal research and burden in a successful program requires clear and consistent communication among all stakeholders--the institutional leadership, institutional animal care and use committee (IACUC), attending veterinarian and staff, and scientists. An evaluation tool is provided for institutions to assess their approach to required and voluntary activities in their animal care program. Drawing on the knowledge and experience gained in a combined 40 years of serving on, managing, training, and evaluating animal care programs, the authors conclude that institutions must thoughtfully balance their research and compliance needs to successfully maintain their institutional goals. They stress that a culture of compliance based on knowledge of the regulations, dedication to quality animal care, reasoned use of science-based performance standards, and the judicious application of professional judgment is the foundation for facilitation of research in the context of animal welfare and regulatory compliance.     

Training strategies for research investigators and technicians

Training programs for research personnel are discussed as a key resource that must be part of an effective animal care and use program. Because of the legal responsibility to ensure that research staff are qualified to use animals, many institutions have justified the necessity for a training coordinator and/or trainers for their animal care and use programs. Effective training programs for research personnel must meet the needs of the client base (research scientists and staff) so that they are relevant, practical, and timely. To meet these objectives, it is useful to involve the scientific staff in the analysis of their learning needs. To meet a performance standard necessary for quality research, a large percentage of the institutional staff must participate in the training program. Often it is the principal investigators who set the tone for their staff members regarding the importance of receiving training. Garnering support from this client base will create a culture that encourages training and engenders a positive attitude about humane animal care and use. One effective approach is to incorporate nonanimal models as alternatives to live animals to teach humane handling techniques and methods, thereby contributing to refinement, reduction, and replacement (the 3Rs). Also discussed are the necessity of timely feedback from clients, documentation of personnel training for regulatory purposes, and the collection of training metrics, which assists in providing justification for the granting of additional fiscal support for the program. Finally, the compliance procedures and opportunities for essential refresher training are discussed and related to high performance standards, humane animal use, and quality research, all of which contribute to the 3Rs.     

Considerations for laboratory animal imaging center design and setup

In vivo animal imaging is an outstanding noninvasive tool to study the pathophysiology of disease or response to therapy; additionally, serial imaging reduces the required number of experimental animals. Because of the tremendous capital investment, we recommend the imaging center be a shared resource to facilitate innovative and productive cross-disciplinary scientific collaborations. A shared center also enables a broader range of imaging, as equipment is often cost prohibitive for smaller facilities. A multitude of factors will determine the architectural design, facility efficiency, and functionality. Important considerations to determine during the planning stages include the types of animals to be imaged, types of imaging studies to be performed, types of imaging equipment and related services to be offered, and the location of the imaging center. Architects must work closely with manufacturers to accommodate equipment-related building specifications; facility planners and veterinarians can provide a practical logistical design that will ensure efficient functionality. Miscellaneous considerations include biosecurity levels, use of radioisotopes, and personnel safety in the imaging environment. The ideal imaging center will include space to house animals and perform necessary preimaging procedures, state-of-the-art in vivo imaging devices and the most up-to-date anesthesia, physiological support, and monitoring equipment. The center staff should include imaging specialists for technical development and data analysis. As it is difficult to provide a comprehensive manual for setting up an in vivo animal imaging center, we offer advice based on our experiences with the National Institutes of Health Mouse Imaging Facility. Because magnetic resonance imaging (MRI) is the most expensive imaging tool, requires specific building design considerations, and poses unique occupational health and safety risks, we focus on MRI as the foundation for an imaging facility design.     

Ambiguous Mice,Speaking Rats: Crossing and Affirming the Great Divides in Scientific Practice

ABSTRACT

During 2009–10, I conducted ethnographic fieldwork with 31 immunologists, virologists, and neuroscientists working with either rats or mice. I encountered how the conceptual and physical bounds that have traditionally separated nature from culture, specie from specie, human from animal, are crossed, blurred, and reasserted. In this ambiguous zone, a scientific incuriosity about animals themselves persists, in the practice of inquiring into animal bodies and minds to produce insights into human health and its betterment. This privileging of human health bypasses animals themselves in favor of a view of them as human similars and prone objects, wholly available to persons, and affirms the Heideggarian thesis, that science occupies an arrogated position in modernity. Such incurious encounters with animals produced ideas and pronouncements about the close biological and genetic similarities that humans and animals share, that scientists in my study called “biokinship” and “genekinship.” These terms indicate both a close relation between animals and persons, but they also present the terms upon which hierarchical relations between humans and animals might be arrayed. Equally present among the scientists with whom I worked was a curiosity about animals themselves. This manifested in understandings and articulations of animals as beings with whom one might make a relationship in which mutually understood communication was possible. Attendant to this curiosity about animals themselves was an awareness scientists in my study had of what these relationships, or what I have called fleshy kinships with rats and mice, might mean for scientific practice, for good science, and for human–animal relatedness in the laboratory. This ambiguous situation calls for analytic attention to biotic materiality and process, but equally for attention to rodents as beings with whom scientists interact on an everyday basis, and with whom they form communicative relations.     

A moderate Buddhist animal research ethics

Though there is a burgeoning interest in applied Buddhist ethics, Buddhist animal research ethics remains an underdeveloped area. In this paper I will explore how some central Buddhist ethical considerations can usefully engage our use of other animals (henceforth, animals) in science. As the scientific use of animals is broad, I will narrow my focus to laboratory science. I will show that, though a Buddhist abolitionism would not be unmotivated, it is possible to reject it. While doing so, it will be important to resist emphasizing elements of Buddhist thought that merely provide reasons to adopt the dominant ethical framework governing laboratory animal research ethics, known as the 3Rs. Though I will suggest how a Buddhist animal research ethics can sometimes permit the use of animals in harmful research, it will also require ethical constraints that resonate with some of the more progressive elements in ‘Western’ bioethics.     

An Hourly Variation in Zoo Visitor Interest: Measurement and Significance for Animal Welfare Research

A methodological difficulty facing welfare research on nonhuman animals in the zoo is the large number of uncontrolled variables due to variation within and between study sites. Zoo visitors act as uncontrolled variables, with number, density, size, and behavior constantly changing. This is worrisome because previous research linked visitor variables to animal behavioral changes indicative of stress. There are implications for research design: Studies not accounting for visitors' effect on animal welfare risk confounding (visitor) variables distorting their findings. Zoos need methods to measure and minimize effects of visitor behavior and to ensure that there are no hidden variables in research models. This article identifies a previously unreported variable—hourly variation (decrease) in visitor interest—that may impinge on animal welfare and validates a methodology for measuring it. That visitor interest wanes across the course of the day has important implications for animal welfare management; visitor effects on animal welfare are likely to occur, or intensify, during the morning or in earlier visits when visitor interest is greatest. This article discusses this issue and possible solutions to reduce visitor effects on animal well-being.