Laboratory animal science issues in the design and conduct of studies with endocrine-active compounds

The use of rodent models for research and testing on endocrine-active compounds necessitates an awareness of a number of laboratory animal science issues to standardize bioassay methods and facilitate reproducibility of results between laboratories. These issues are not unique to endocrine research but are particularly important in this field due to the complexities and interdependencies of the endocrine system, coupled with the inherently sensitive and variable nature of physiological endpoints. Standardization of animal models and the control of animal environments depend on the establishment of strong scientific partnerships between research investigators and laboratory animal scientists. Laboratory animal care and use programs are becoming increasingly complex and are constantly changing, fueled in part by technological advances, changes in regulations concerning animal care and use, and economic pressures. Since the early 1980s, many institutions have moved to centralization of animal facility operations concomitant with numerous changes in housing systems, barrier concepts, equipment, and engineering controls of the macro- and microenvironment. These and other changes can have an impact on animals and the conduct of endocrine experiments. Despite the potential impact of animal care and use procedures on research endpoints, many investigators are surprisingly naive to the animal facility conditions that can affect in vivo studies. Several key animal care and use issues that are important to consider in endocrine experiments with rodent models are described.     

Postapproval monitoring and the IACUC

Monitoring of the use of live vertebrate animals in research, teaching, and testing after approval of their use by an institutional animal care and use committee (IACUC) are receiving increased attention in the laboratory animal community. In this article the author provides his opinions on the value of postapproval monitoring (PAM) to the overall self-regulation that is the responsibility of an IACUC. PAM must never supersede or replace federally mandated IACUC responsibilities, but an efficient PAM process can provide significant additional information that enables an institution to be confident that it is meeting both the letter and the spirit of the federal regulations developed to ensure humane animal care. PAM personnel should be excellent communicators and able to maintain a professional demeanor in challenging circumstances. Their knowledge of laboratory animal care, invasive procedures, and regulations will enable them to align the pursuit of scientific research with adherence to these regulations. An effective PAM program involves knowledgeable individuals who can, on behalf of the IACUC, monitor new procedures and personnel and provide IACUC-mandated training or retraining.     

Genetic engineering and other factors that might affect human-animal interactions in the research setting

Evidence exists, particularly in the welfare literature of nonhuman animals on the farm, that the interaction between nonhuman animals and the personnel who care for them can have a strong effect on the animals' behavior, productivity, and welfare. Among species commonly used for biomedical research, mice appear to be the least-preferred species in animal care facilities. A review of the literature and observations of animal care staff interacting with mice indicated that the following factors may influence this: their small size, their particular behavioral characteristics, and husbandry constraints (such as housing in ventilated racks). In addition, this study questioned whether animal care personnel have a different perception of genetically engineered animals and whether this, in turn, has an effect on their interactions with these animals. The ability to carefully observe an animal's behavior is key in carrying out an animal-wellness assessment and in minimizing pain and distress. Attention to human-animal interactions in the research setting represents an opportunity for refinement for large numbers of animals and potentially for reduction of animal use.     

Genetic Engineering and Other Factors That Might Affect Human-Animal Interactions in the Research Setting

Evidence exists, particularly in the welfare literature of nonhuman animals on the farm, that the interaction between nonhuman animals and the personnel who care for them can have a strong effect on the animals' behavior, productivity, and welfare. Among species commonly used for biomedical research, mice appear to be the least-preferred species in animal care facilities. A review of the literature and observations of animal care staff interacting with mice indicated that the following factors may influence this: their small size, their particular behavioral characteristics, and husbandry constraints (such as housing in ventilated racks). In addition, this study questioned whether animal care personnel have a different perception of genetically engineered animals and whether this, in turn, has an effect on their interactions with these animals. The ability to carefully observe an animal's behavior is key in carrying out an animal-wellness assessment and in minimizing pain and distress. Attention to human-animal interactions in the research setting represents an opportunity for refinement for large numbers of animals and potentially for reduction of animal use.     

Animal care and use issues in movement disorder research

Animal models of movement disorders can present special challenges for the research institutions that use them. Such models often affect the animals' ability to ambulate and perform normal body functions, and these potential effects on health and well-being mandate additional steps to ensure humane animal care and use. Indeed, the appropriate level of care for these models may call for actions that go beyond what is required or considered standard for other protocols. A proactive team approach to animal use protocol development and animal management is important. Through the commitment and involvement of the entire team-researchers, facility personnel, and institutional animal care and use committee members--institutions that use these valuable models can ensure both the fulfillment of research objectives and the implementation of the best practices for animal care. Among the most commonly used animal models of movement disorder are models of stroke, brain and spinal cord injury, dystonia, Parkinson's disease, and Huntington's disease. Despite their relatively wide use, there is very little in the literature that describes the specific needs of individual models and the challenges those needs may present in today's regulatory environment. In this article, we discuss animal use considerations and provide the available animal care information on specific models. Interested readers are also referred to the additional information in the accompanying articles in this issue of ILAR Journal.     

Animal models of ischemic stroke: balancing experimental aims and animal care

Animal models of ischemic stroke are examples of an induced model that can present challenges from the perspectives of protocol review and animal management. The review presented here will include a brief summary of the current state of knowledge about clinical stroke; a general synopsis of important unanswered research questions that justify use of animal stroke models; an overview of various animal models of ischemic stroke, including strengths and limitations; and a discussion of animal care issues relative to ischemic stroke models. Good communication and interactive education among primary investigators, laboratory animal veterinarians and caretakers, and institutional animal care and use committee members are critical in achieving a balance between research objectives and animal care issues when using animal stroke models.     

Applying the principles of disaster prevention to decrease adverse events in a research program

In an animal care and use program in a research setting, events that have a negative impact on animal well-being do not typically occur spontaneously and arbitrarily. It takes the convergence of multiple missteps, miscalculations and misinterpretations of conditions for a serious accident to take place. Two concepts drawn from wilderness survival training can be applied to any research animal care and use program to reduce adverse events. The first, derived from the accident matrix model, is the concept of 'problem vectors,' or conditions, behaviors and policies that increase the likelihood of an adverse event. Identifying problem vectors and diverting them before they intersect to create an adverse event can considerably improve animal well-being and reduce the number of protocol violations and reportable events. The second concept is that of doing the 'next right thing' when an adverse event does occur in an animal program. The next right thing is a response characterized by unified directed action toward fixing problems without engaging in behaviors that might worsen the situation. Adopting an institution-wide approach of diverting problem vectors and pursuing the next right thing can result in better prevention and management of adverse events.     

浅论实验动物兽医的职责及实践

随着我国实验动物科学和动物试验的迅速发展,实验动物兽医的需求越来越大。实验动物兽医的角色多种多样,广义地讲可以是任何具有兽医资质且从事实验动物管理、繁育、疾病诊断防治、动物试验和研究的人员。通常实验动物兽医是指实验动物临床兽医或实验动物主管兽医。实验动物兽医的天职是确保动物的健康和福利,并支持高质量的动物试验研究。本文从实验动物兽医工作的必要性、实验动物兽医的发展、实验动物兽医的资质、职责等几个方面,并结合合同外包研发机构中兽医的实践阐述了实验动物兽医的工作性质、任务和内容。     

Guidelines for the veterinary care of laboratory animals: report of the FELASA/ECLAM/ESLAV Joint Working Group on Veterinary Care

Veterinary professionals working in partnership with other competent persons are essential for a successful animal care and use programme. A veterinarian's primary responsibilities are defined by their own professional regulatory bodies, but in this area of work there are further opportunities for contribution, which will assist in safeguarding the health and welfare of animals used in research. These guidelines are aimed not only at veterinarians to explain their duties, and outline the opportunities to improve the health and welfare of animals under their care, but also at employers and regulators to help them meet their responsibilities. They describe the desirability for postgraduate education towards specialization in laboratory animal medicine and detail the many competencies necessary to fulfil the role of the laboratory animal veterinarian. They detail the need for veterinary expertise to promote good health and good welfare of animals used in biomedical research during husbandry as well as when under experimental procedures. Regulatory and ethical aspects are covered as are the involvement of the veterinarian in education and training of others working in the animal care and use programme. Managerial aspects, including occupational health and safety, are also areas where the veterinarian's input can assist in the successful implementation of the programme.     

The Study Support Associate: an alternative to the traditional animal care position

The authors describe the development of a position in animal care that combines husbandry, veterinary care, breeding colony management, and in vivo research support. The integration of these tasks gives participating animal care staff more diverse responsibilities and leads to more effective communication and collaboration between researchers and husbandry personnel.     

The role of the veterinary staff in mouse breeding colony management

The rapid increase in the production and use of transgenic mice has been a boon for biomedical research and a challenge for the animal care and use programs responsible for providing housing and medical care to these animals. The authors suggest ways in which the veterinary staff can successfully organize and manage transgenic mouse breeding programs to reduce uncontrolled breeding and the problems associated with it.     

Selection, acclimation, training, and preparation of dogs for the research setting

Dogs have made and will continue to make valuable contributions as animal models in biomedical research. A comprehensive approach from time of breeding through completion of in-life usage is necessary to ensure that high-quality dog models are used in studies. This approach ensures good care and minimizes the impact of interanimal variability on experimental results. Guidance related to choosing and developing high-quality laboratory dogs and managing canine research colonies is provided in this article. Ensuring that dogs are healthy, well adapted, and cooperative involves good communication between vendors, veterinarians, care staff, and researchers to develop appropriate dog husbandry programs. These programs are designed to minimize animal stress and distress from the postweaning period through the transfer and acclimation period within the research facility. Canine socialization and training programs provided by skilled personnel, together with comprehensive veterinary health programs, can further enhance animal welfare and minimize interanimal and group variability in studies.     

Development of the piglet neonatal intensive care unit for translational research

The piglet is an important animal model in biomedical research; many aspects of its anatomy, physiology and metabolism are similar to those of the human neonate. The authors describe a neonatal intensive care unit (NICU) for piglets. This unit allows researchers to model neonatal care in the NICU and can be used for a range of research studies. The authors hope that the model they describe can serve as a template for other investigators who would like to design their own piglet NICUs.     

A guide to defining and implementing protocols for the welfare assessment of laboratory animals: eleventh report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement

The refinement of husbandry and procedures to reduce animal suffering and improve welfare is an essential component of humane science. Successful refinement depends upon the ability to assess animal welfare effectively, and detect any signs of pain or distress as rapidly as possible, so that any suffering can be alleviated. This document provides practical guidance on setting up and operating effective protocols for the welfare assessment of animals used in research and testing. It sets out general principles for more objective observation of animals, recognizing and assessing indicators of pain or distress and tailoring these to individual projects. Systems for recording indicators, including score sheets, are reviewed and guidance is set out on determining practical monitoring regimes that are more likely to detect any signs of suffering. This guidance is intended for all staff required to assess or monitor animal welfare, including animal technologists and care staff, veterinarians and scientists. It will also be of use to members of ethics or animal care and use committees. A longer version of this document, with further background information and extra topics including training and information sharing, is available on the Laboratory Animals website.     

Program oversight enhancements (POE): the big PAM

Federal animal welfare regulations and policies require compliance during animal research. But the methods used to oversee, assess, and ascertain compliance are left in the hands of the research institution and its institutional animal care and use committee (IACUC). Differences in institutional cultures, research goals, individuals responsible for animal care and use activities and oversight, and availability of financial and personnel resources have given rise to a variety of institution-specific mechanisms for ensuring compliance with the federal requirements and specifically with IACUC-approved animal research activities. In recent years one such mechanism, postapproval monitoring (PAM), has risen in popularity. An often cited topic in animal welfare-related conferences and periodicals, it is well on its way to becoming a compliance standard. However, it is but one mechanism for ensuring postapproval compliance and is not required by the federal animal welfare regulations. In this article we describe alternative mechanisms for ensuring compliance with IACUC-approved animal research through the use of program oversight enhancements (POE) in the context of an institution's animal care and use program. We present these enhancements in a way that allows readers to pick and choose those of interest. While these methods may not be feasible at all institutions, adopting even a few should improve a program's ability to ensure compliance with approved animal research and reduce the need for an aggressive and formal postapproval monitoring process.     

Technical team approaches to rodent care: cost savings, reduced risk, and improved stewardship

With the increasing decentralization of animal care operations, lack of training and higher-density animal rooms make achieving humane assurances difficult. To offset these problems, some facilities have developed centralized animal care programs, including dispersed teams of qualified animal care specialists.     

Food for Thought: Assessing Visitor Comfort and Attitudes toward Carcass Feeding at the ABQ BioPark Zoo

Enrichment is a key to keeping animals in zoos healthy and stimulated. For carnivores, the practice of feeding vertebrate animal carcasses, like those of goats or deer, or whole body prey animals like chickens or rabbits, can be an effective form of enrichment. While it is beneficial for animal care, carcass feeding may also be off-putting to some visitors. This research aimed to address this concern by describing the attitudes and comfort levels of visitors who viewed carcass feeding in three exhibits at the ABQ BioPark Zoo in Albuquerque, New Mexico: spotted hyena (Crocuta crocuta), Tasmanian devil (Sarcophilus harrisii), and African painted dog (Lycaon pictus). Results showed that visitors stayed at exhibits longer when a carcass was introduced and reported feeling generally comfortable and at ease while viewing carcass feeding. Findings also showed that visitors felt carcass feeding was beneficial to animal care and welfare.     

Sexual conflict over parental care promotes the evolution of sex differences in care and the ability to care

Strong asymmetries in parental care, with one sex providing more care than the other, are widespread across the animal kingdom. At present, two factors are thought to ultimately cause sex differences in care: certainty of parentage and sexual selection. By contrast, we here show that the coevolution of care and the ability to care can result in strong asymmetries in both the ability to care and the level of care, even in the absence of these factors. While the coevolution of care and the ability to care does not predict which sex evolves to care more than the other, once other factors give rise to even the slightest differences in the cost and benefits of care between the sexes (e.g. differences in certainty in parentage), a clear directionality emerges; the sex with the lower cost or higher benefit of care evolves both to be more able to care and to provide much higher levels of care than the other sex. Our findings suggest that the coevolution of levels of care and the ability to care may be a key factor underlying the evolution of sex differences in care.     

In pursuit of peak animal welfare; the need to prioritize the meaningful over the measurable

Despite the diversity of animal welfare definitions, most recognise the centrality of the feelings of animals which are currently impossible to measure directly. As a result, animal welfare assessment is heavily reliant upon the indirect measurement of factors that either affect what animals feel, or are effected by how they feel. Physiological and health orientated measures have emerged as popular metrics for assessing welfare because they are quantifiable, can effect and be affected by how animals feel and have merits regardless of their relationship to the feelings of animals. However, their popularity in animal welfare assessment has led to them having a disproportionate influence on animal management to the detriment of animal welfare in numerous instances. Here, the case is made that a tension exists between management that prioritizes aspects of care reflecting popular animal welfare metrics such as those relating to physical health, and management that emphasizes psychological wellbeing. By re‐examining the relative merits of physical and psychological priorities in animal management, an alternate animal welfare paradigm emerges less tied to traditional welfare metrics. This paradigm theorizes about the possibility for an optimal animal welfare state to exist where managed animal populations provided essential psychological outlets but protected from key physical stressors routinely experienced in the wild, might experience higher levels of welfare than wild populations would routinely experience. The proposition that optimal animal welfare could theoretically be achieved in well managed and well designed captive environments challenges a widely held ethical perspective that captivity is inherently bad for animal welfare.