Institutional responsibilities in contamination control in research animals and occupational health and safety for animal handlers

The mechanisms for controlling microbial contamination in research animals are similar to those for preventing exposure among animal handlers to naturally occurring pathogens, research-related biohazards, or animal allergens. Research and resource preservation are the primary goals of each approach, and an appropriate assessment of risk is their foundation. The identification of potential risks enables the implementation of relevant risk management or control measures. This article summarizes the components of an occupational health and safety program for animal handlers, including screening, training, work practices, effective use of engineering controls, selection and use of personal protective equipment, and emergency response protocols. The features of a risk assessment and risk management program and the level of interaction and training required to implement and sustain the program correlate well with programs designed to control microbial contamination in laboratory animals. This article includes an explanation of the five Ps of risk assessment and risk management. Pathogens and the proposed experimental procedures account for the first two Ps; the other three focus on training and awareness of the personnel involved in the experiment, protective equipment and work practices, and factors associated with the place (or facility) where the research will be conducted. Animal handlers comprehension and knowledge determine the success of any containment program, and so this review also includes a discussion of critical teaching points for animal handlers and of the importance of evaluating personnel to verify their proficiency and competence in required protocols.     

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.     

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.     

A training primer for Institutional Officials

The laws and policies governing the care and use of animals in research in the US require institutions to establish training programs to assure that personnel are qualified for their roles in animal care and use programs. Few programs define specific training requirements for the Institutional Official (IO), one of the most important roles in an animal care program. In some cases, IOs may have little or no experience in biomedical science. In this article, the author provides an overview of the IO's role in an animal care and use program as defined by US government laws and policies for use in training IOs and chief executive officers. The author outlines the key responsibilities of the IO in an animal care program, the implications of noncompliance with federal requirements and some of the pitfalls in program design.     

Preparing chimpanzees for laboratory research

The chimpanzee is the only representative of the Great Apes that is extensively involved in biomedical research in primate laboratories. These apes are used as animal models in a variety of studies, including research on infectious disease, parasitic disease, pharmacokinetic studies, neuroscience, cognition, and behavior. Chimpanzees used in biomedical research in the United States reside largely in six specialized research and holding facilities, and most of the research with them is conducted at these sites. Given the relatively small population of chimpanzees and its importance to biomedical research, it is imperative that we carefully manage the care, production, and use of these animals in biomedical research studies. Selection criteria and preparation techniques are reviewed in this article in an effort to begin a discussion on best practices for choosing and handling chimpanzees participating in biomedical research. The use of routine health assessment information is described for subject selection, as are behavioral issues to be considered. Due to the relatively small number of chimpanzees available, issues related to experimental design and multiple uses of chimpanzees are discussed. Practices related to the transportation and acclimation of chimpanzees are described. Finally, behavioral conditioning procedures are discussed, including habituation, desensitization, and positive reinforcement training that have been applied to reduce animal distress and improve the quality of the science being conducted with chimpanzee subjects.     

Fundamental training for individuals involved in the care and use of laboratory animals: a review and update of the 1991 NRC Core Training Module

Public trust demands that individuals who do research, testing, or teaching with animals use humane, ethical, and scientifically sound methods. Furthermore, the Animal Welfare Act and the Public Health Service Policy require research institutions to provide basic training and to ensure that anyone who cares for and/or works with laboratory animals has the appropriate training or experience relevant to their job responsibilities. Institutions accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International must also provide training programs and ensure the qualifications of personnel. The primary goal of this training is to provide individuals with basic knowledge and to reinforce attitudes and behaviors that help to ensure humane animal care and use. This article provides an overview of the core training module outline and content from the 1991 report of the Institute for Laboratory Animal Research, Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs, as well as pertinent updates for introducing personnel to information regarding the care and use of laboratory animals. Both mandatory and suggested training topics are reviewed, including relevant regulations and standards, ethical considerations, humane methods of animal experimentation and maintenance, and other pertinent topics. Although the fundamental training course content and delivery will vary depending on the nature and complexity of an institution's animal care and use program, this basic training provides the foundation for more in-depth training programs and supports humane and ethical animal care and use.     

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.     

Training strategies for laboratory animal veterinarians: challenges and opportunities

The field of laboratory animal medicine is experiencing a serious shortage of appropriately trained veterinarians for both clinically related and research-oriented positions within academia, industry, and government. Recent outreach efforts sponsored by professional organizations have stimulated increased interest in the field. It is an opportune time to critically review and evaluate postgraduate training opportunities in the United States and Canada, including formal training programs, informal training, publicly accessible training resources and educational opportunities, and newly emerging training resources such as Internet-based learning aids. Challenges related to each of these training opportunities exist and include increasing enrollment in formal programs, securing adequate funding support, ensuring appropriate content between formal programs that may have diverse objectives, and accommodating the training needs of veterinarians who enter the field by the experience route. Current training opportunities and resources that exist for veterinarians who enter and are established within the field of laboratory animal science are examined. Strategies for improving formal laboratory animal medicine training programs and for developing alternative programs more suited to practicing clinical veterinarians are discussed. In addition, the resources for high-quality continuing education of experienced laboratory animal veterinarians are reviewed.     

Identification of key concepts in biomedical literature using a modified Markov heuristic

MOTIVATION: The recent explosion of interest in mining the biomedical literature for associations between defined entities such as genes, diseases and drugs has made apparent the need for robust methods of identifying occurrences of these entities in biomedical text. Such concept-based indexing is strongly dependent on the availability of a comprehensive ontology or lexicon of biomedical terms. However, such ontologies are very difficult and expensive to construct, and often require extensive manual curation to render them suitable for use by automatic indexing programs. Furthermore, the use of statistically salient noun phrases as surrogates for curated terminology is not without difficulties, due to the lack of high-quality part-of-speech taggers specific to medical nomenclature. RESULTS: We describe a method of improving the quality of automatically extracted noun phrases by employing prior knowledge during the HMM training procedure for the tagger. This enhancement, when combined with appropriate training data, can greatly improve the quality and relevance of the extracted phrases, thereby enabling greater accuracy in downstream literature mining tasks.     

Red-carpet rodent care: making the most of dollars and sense in the animal facility

Cutting-edge biomedical research programs have entered an era in which phenotypic characterizations for genetically altered rodents can facilitate appropriate care. The veterinary care requirements necessary to support such animal models can include the procedures already adapted as standard practice in companion animal hospitals, and can decrease data variability while increasing survival rates.     

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.     

The Yucatan miniature pig: characterization and utilization in biomedical research

Yucatan miniature swine have a variety of applications in biomedical research. Sublines developed from the primary population at Colorado State University have been characterized genetically with special attributes. This report describes this unique laboratory animal, genetic selection programs, and its utilization in biomedical research.     

Training for best practices for agricultural programs

As with other areas of animal research, ensuring the proper training and qualifications of the individuals working with agricultural animals for use in research, teaching, and testing is critical to both animal welfare and the successful outcome of the study or teaching exercise. The author provides guidance for the development of appropriate training programs for organizations that use agricultural animals in research.     

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.     

Engineering excellence in breakthrough biomedical technologies: bioengineering at the University of California, Riverside

The Department of Bioengineering at the University of California, Riverside (UCR), was established in 2006 and is the youngest department in the Bourns College of Engineering. It is an interdisciplinary research engine that builds strength from highly recognized experts in biochemistry, biophysics, biology, and engineering, focusing on common critical themes. The range of faculty research interests is notable for its diversity, from the basic cell biology through cell function to the physiology of the whole organism, each directed at breakthroughs in biomedical devices for measurement and therapy. The department forges future leaders in bioengineering, mirroring the field in being energetic, interdisciplinary, and fast moving at the frontiers of biomedical discoveries. Our educational programs combine a solid foundation in bio logical sciences and engineering, diverse communication skills, and training in the most advanced quantitative bioengineering research. Bioengineering at UCR also includes the Bioengineering Interdepartmental Graduate (BIG) program. With its slogan Start-Grow-Be-BIG, it is already recognized for its many accomplishments, including being third in the nation in 2011 for bioengineering students receiving National Science Foundation graduate research fellowships as well as being one of the most ethnically inclusive programs in the nation.     

Graduate Students and Knowledge Exchange with Local Stakeholders: Possibilities and Preparation

Tropical biologists are exploring ways to expand their role as researchers through knowledge exchange with local stakeholders. Graduate students are well positioned for this broader role, particularly when supported by graduate programs. We ask: (1) how can graduate students effectively engage in knowledge exchange during their research; and (2) how can university programs prepare young scientists to take on this partnership role? We present a conceptual framework with three levels at which graduate students can exchange knowledge with stakeholders (information sharing, skill building, and knowledge generation) and discuss limitations of each. Examples of these strategies included disseminating preliminary research results to southern African villages, building research skills of Brazilian undergraduate students through semester‐long internships, and jointly developing and implementing a forest ecology research and training program with one community in the Amazon estuary. Students chose strategies based on stakeholders' interests, research goals, and a realistic evaluation of student capacity and skill set. As strategies became more complex, time invested, skills mobilized, and strength of relationships between students and stakeholders increased. Graduate programs can prepare students for knowledge exchange with partners by developing specialized skills training, nurturing external networks, offering funding, maximizing strengths of universities in developed and developing regions through partnership, and evaluating knowledge exchange experiences. While balancing the needs of academia with those of stakeholders is challenging, the benefits of enhancing local scientific capacity and generating more locally relevant research for improved conservation may be worth the risks associated with implementing this type of graduate training model.     

Informed Consent in Cross-cultural Perspective: Clinical Research in the Tibetan Autonomous Region, PRC

Procedures of Informed Consent are considered a high priority for international biomedical research. However, informed consent protocols are not necessarily transferable across cultural, national or ethnic groups. Recent debates identify the need for balancing ethical universals with practical and local conditions and paying attention to questions of cultural competence when it comes to the Informed Consent process for clinical biomedical research. This article reports on the results of a two-year effort to establish a culturally appropriate Informed Consent process for biomedical research in the Tibet Autonomous Region in the People's Republic of China. A team of Tibetan and American researchers, physicians, health professionals and medical anthropologists conducted the research. The Informed Consent was specifically for undertaking a triple-blind, double placebo-controlled randomized clinical trial of a Tibetan medicine compared with Misoprostol for reducing postpartum blood loss. The findings suggest greater need for flexibility and cooperation in establishing Informed Consent protocols across cultures and nations.     

Rodent quarantine programs: purpose, principles, and practice

In animal research, validity and reproducibility of data are critically influenced by the microbial status of the experimental animals. One of the most crucial aspects of assuring quality in animal research is providing research personnel with confidence that experimental results will not be invalidated due to interference caused by infectious disease. An effective quarantine program is essential to providing this assurance. Quarantine programs are generally instituted to prevent the introduction of rodent pathogens into established specific-pathogen-free colonies in a facility. Therefore, programs should be designed to isolate newly acquired rodents until their health status can be determined and to maximize the probability that microorganisms of interest will be detected before the animals are introduced into (and thus, could potentially contaminate) established colonies. Important principles that are critical to designing an effective quarantine program will be discussed here, as will the practical implementation of these principles. Although quarantine programs may be costly in terms of time and effort, these costs must be balanced against the potential costs of disease outbreaks that could invalidate long-term studies, alter normal biological baselines, and cause the loss or necessitate re-derivation of rare or valuable strains of rodents. Reducing the incidence of quarantine failures through appropriate program design and implementation helps to maintain the confidence of research personnel in the value of quarantine programs and in our competence as specialists in laboratory animal management and as partners in the research process.     

The poor contribution of chimpanzee experiments to biomedical progress

Biomedical research on captive chimpanzees incurs substantial nonhuman animal welfare, ethical, and financial costs that advocates claim resultin substantial advancements in biomedical knowledge. However, demonstrating minimal contribution toward the advancement of biomedical knowledge generally, subsequent papers did not cite 49.5% (47/95), of 95 experiments randomly selected from a population of 749 published worldwide between 1995 and 2004. Only 14.7% (14/95) were cited by 27 papers that abstracts indicated described well-developed methods for combating human diseases. However, detailed examination of these medical papers revealed that in vitrostudies, human clinical and epidemiological studies, molecular assays and methods, and genomic studies contributed most to their development. No chimpanzee study made an essential contribution, or, in most cases, a significant contribution of any kind, to the development of the medical method described. The approval of these experiments indicates a failure of the ethics committee system. The demonstrable lack of benefit of most chimpanzee experimentation and its profound animal welfare and bioethical costs indicate that a ban is warranted in those remaining countries—notably the United States—that continue to conduct it.     

Graduate education and the role of the physical anthropologist in biomedical teaching and research

There is a place for the physical anthropologist in biomedical teaching and research because of the special and unique skills possessed by this individual. However, eventual success in the health sciences environment requires the student to obtain the knowledge and background for functionally oriented teaching and research. Students interested in a biomedical teaching and research career must prepare themselves methodologically and theoretically. This requires: (1) teaching qualifications, (2) an increased emphasis on methodology and technology, (3) an increased emphasis on research and experimental design, (4) appropriate interdisciplinary courses which provide the background for both teaching and research, (5) increased interaction with graduate faculty active in research, and (6) the latitude to adapt the graduate program to meet these specific needs. Students who finish their graduate training with a marketable skill, and who can apply their unique talents to a specialized area, will have broad appeal in the job market and will considerably strengthen their career opportunities.