Harm-benefit analyses (HBAs) are becoming de rigueur with some governmental regulatory agencies and popular with local institutional animal care and use committees (or their equivalents), the latter due, in part, to the adoption of HBAs as an international accreditation standard. Such analyses are employed as an attempt to balance potential or actual pain or distress imposed on laboratory animals against

The use of animal models remains critical in preclinical and translational research. The reliability of the animal models and aspects of their validity is likely key to effective translation of findings to medicine. However, despite considerable uniformity in animal models brought about by control of genetics, there remain a number of social as well as innate and acquired behavioral characteristics

This article appeals to virtue ethics to help guide laboratory animal research by considering the role of character and flourishing in these practices. Philosophical approaches to animal research ethics have typically focused on animal rights or on the promotion of welfare for all affected, while animal research itself has been guided in its practice by the 3Rs (reduction, refinement, replacement)

For more than 50 years, the research community has made strides to better determine the nutrient requirements for many common laboratory animal species. This work has resulted in high-quality animal feeds that can optimize growth, maintenance, and reproduction in most species. We have a much better understanding of the role that individual nutrients play in physiological responses. Today, diet is often

Our bodies and those of our animal research subjects are colonized by bacterial communities that occupy virtually every organ system, including many previously considered sterile. These bacteria reside as complex communities that are collectively referred to as microbiota. Prior to the turn of the century, characterization of these communities was limited by a reliance on culture of organisms on a

“Animal-based research should be held to the highest ethical standards” is becoming an increasingly common refrain. Though I think such a commitment is what we should expect of those using animals in science, much as we would if the participants were humans, some key insights of discussions in applied ethics and moral philosophy only seem to slowly impact what reasonably qualifies as the highest standards

Sound and vibration have been shown to alter animal behavior and induce physiological changes as well as to cause effects at the cellular and molecular level. For these reasons, both environmental factors have a considerable potential to alter research outcomes when the outcome of the study is dependent on the animal existing in a normal or predictable biological state. Determining the specific levels

Light is a key extrinsic factor to be considered in operations and design of animal room facilities. Over the past four decades, many studies on typical laboratory animal populations have demonstrated impacts on neuroendocrine, neurobehavioral, and circadian physiology. These effects are regulated independently from the defined physiology for the visual system. The range of physiological responses

Summary: Review of the use of nonexperimental xenobiotics in terrestrial animal models and the potential unintended consequences of these compounds, including drug-related side effects and adverse reactions.

Reproducible and reliable scientific investigation depends on the identification and consideration of various intrinsic and extrinsic factors that may affect the model system used. The impact of these factors must be managed during all phases of a study: planning, execution, and reporting. The value of in vivo (animal) research has come under increasing scrutiny over the past decade because of multiple

AbstractThis issue of the ILAR Journal focuses on the topic of responsible science as it relates to animal research. We start with the concept of the scientist as a responsible citizen and then move through multiple phases of research including careful experimental planning, reporting, and incorporation of laboratory animal science. The work of the Institutional Animal Care and Use Committee (IACUC)

Environmental complexity is an experimental paradigm as well as a potential part of animals' everyday housing experiences. In experimental uses, researchers add complexity to stimulate brain development, delay degenerative brain changes, elicit more naturalistic behaviors, and test learning and memory. Complexity can exacerbate or mitigate behavioral problems, give animals a sense of control, and allow

The publication of reproducible, replicable, and translatable data in studies utilizing animal models is a scientific, practical, and ethical necessity. This requires careful planning and execution of experiments and accurate reporting of results. Recognition that numerous developmental, environmental, and test-related factors can affect experimental outcomes is essential for a quality study design

The significance of ethical considerations for animal research policy has long been acknowledged, but the role of philosophical ethics in the policymaking process has been less clear. By comparing the ethical framework of animal research policy with that for human subjects research, this article considers how the legacies of these two policy areas influence current policy and suggests that ethicists

Rapid advances in gene-editing and stem-cell technology have expanded the range of possible future applications in human-animal chimera research. Most notably, recent developments may allow researchers to generate whole personalized human organs in pigs for the purpose of transplantation into human patients. Though human-animal chimera research in small animals, such as mice, is routine, human-animal

Most would agree that animals in research should be spared "unnecessary" harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard of care that we should aspire to? We argue that we need to work towards a higher standard-specifically, that providing research animals with a "good life" should be a prerequisite

As mentioned in other chapters, reproducibility of research data is very complicated and has numerous contributors for concerns. This chapter will discuss the animal housing systems and corresponding husbandry practices in regard to current practices and known and potential confounders in the research environment. This area has a very high impact for reproducibility and comparability of study data

The focus of this paper is the requirement that the use of live animals in experiments and in vivo assays should never be allowed if those uses involve severe suffering. This requirement was first implemented in Danish legislation, was later adopted by the European Union, and has had limited uptake in North America. Animal suffering can arise from exposure to a wide range of different external and

This issue of the ILAR Journal focuses on the topic of responsible science as it relates to animal research. We start with the concept of the scientist as a responsible citizen and then move through multiple phases of research including careful experimental planning, reporting, and incorporation of laboratory animal science. The work of the Institutional Animal Care and Use Committee (IACUC) or animal

The scientific enterprise satisfies the innate human urge to understand the world; these efforts have led to both improvements and dangers to society. The storied history of relationships between scientists and citizens suggests that the lines between these 2 sectors of society are often blurred. Here we discuss these relationships on the context of animal welfare. We briefly outline the history of

IACUCResearch animal welfareResponsible animal research

Biomedical research has made great strides in the past century leading to rapid advances in human life expectancy, all derived from improved understanding, prevention, and treatment of many diseases and conditions. Research involving laboratory animals has played a significant role in this medical progress. However, there continues to be controversy surrounding the use of animals in research, and animal

Increasing focus on issues of research reproducibility affords us the opportunity to review some of the key issues related in vivo research. First, we set out some key definitions, to guide the reader through the rest of the paper. Next we consider issues of epistemology, of how animal experiments lead to changes in our understanding of biomedicine and, potentially, to the development of new therapeutics

Research with animals presents a wide array of hazards, some of which overlap those in the in vitro research laboratory. The challenge for environmental health and safety professionals when making their recommendations and performing the risk assessment is to balance worker safety with animal safety/welfare. The care and husbandry of animals require procedures and tasks that create aerosols and involve

There have been recent efforts to reduce the administrative burden imposed on investigators. Although a complete and thorough review of proposed animal studies is an essential function of the Institutional Animal Care and Use Committee (IACUC), efforts to streamline and clarify this process may help investigators spend less time writing animal use protocols and responding to committee comments. The

Animals play a key role in biomedical research and other areas of scientific inquiry. But public opinion plays a key role in influencing how this area of science is regulated and funded. Nevertheless, scientists have historically been reticent to speak openly about their animal research or to open their animal facilities to the public in any way. Consequently, most of the available information has

In fiscal year 2016, agricultural animals such as swine, sheep, goats, and cattle represented 10% of the 820 812 animals used in USDA-regulated research. In addition to traditional agricultural animals, research studies using captive wildlife are becoming increasingly important as human and livestock populations encroach upon, and thus expand interactions with, wildlife populations on the landscape

The authors discuss approaches to bolster investigator engagement, inviting investigators to be partners within the Animal Care Program. Regulatory burden in animal research endeavors continues to be reviewed and critiqued; therefore, this article intends to encourage Animal Care Programs to promote transparency and incorporation of unique educational training initiatives to tailor and focus compliance

Institutional Animal Care and Use Committees (IACUCs) occasionally face regulatory requirements for which clear guidance may not be available. Either the regulating body has chosen not to provide such guidance or the guidance may be minimal or even ambiguous. Such guidance may be desirable when institutions have research needs, in which case IACUCs are left to their own interpretation to develop internal

Disaster preparedness for research facilities can be a daunting task. The purpose of this review is to introduce basic preparedness concepts and terminology so that facilities may begin to develop customized plans for their specific needs. Regulatory requirements are reviewed and an overview of the Incident Command System, National Preparedness System Planning Frameworks, and fundamental terms is provided

Globalization of the biomedical research enterprise is occurring at an accelerating pace. Increasingly, scientific collaborations and contracts cross national borders. Assurance that the caliber of animal research and animal welfare are consistent among countries and that such animal use is done in a humane and conscientious manner is of significant concern to the scientific community, the general

Valid interpretation of preclinical animal models in immunology-related clinical challenges is important to solve outstanding clinical needs. Given the overall complexity of the immune system and both species- and tissue-specific immune peculiarities, the selection and design of appropriate immune-relevant animal models is, however, not following a straightforward path. The topics in this issue of

This issue of ILAR Journal focusses on pathology and pathologists in biomedical research, more specifically in preclinical translational research involving (nonhuman) animals, emphasizing academic settings. Considerations in study design and planning to maximize benefit from pathologists and pathology resources are reviewed. Adjunctive technologies including molecular techniques, digital pathology

In 1989 ILAR published a list and description of immunodeficient rodents used in research. Since then, advances in understanding of molecular mechanisms; recognition of genetic, epigenetic microbial, and other influences on immunity; and capabilities in manipulating genomes and microbiomes have increased options and opportunities for selecting mice and designing studies to answer important mechanistic

Enterotoxigenic Escherichia coli (ETEC) is the major etiological agent causing acute watery diarrhea that is most frequently seen in young children in lower-income countries. The duration of diarrheal symptom may be shortened by antibiotic treatment, but ETEC is relative refractory to common antibiotics. Burgeoning evidence suggests bioactive components that naturally occur in human milk (e.g., lysozyme

The cellular immunotherapy field has achieved important milestones in the last 30 years towards the treatment of a variety of cancers due to improvements in ex-vivo T cell manufacturing processes, the invention of synthetic T cell receptors, and advances in cellular engineering. Here, we discuss major preclinical models that have been useful for the validation of chimeric antigen receptor (CAR)-T cell

Institutions with animal care and use programs are obligated to provide for the health and well-being of the animals, but are equally obligated to provide for safety of individuals associated with the program. The topics in this issue of the ILAR Journal, in association with those within the complimentary issue of the Journal of Applied Biosafety, provide a variety of contemporary occupational health

Disaster response planning for laboratory animal facilities is a time- and personnel-intensive undertaking. This article outlines numerous considerations in formulating a plan for disaster response in a high containment animal unit. The planning process is discussed around a set of elements: planning team formation, situational understanding, goal and objective determination, plan development, preparation

Animal research pathology encompasses a wide array of procedures and may involve work with a variety of animal species and hazards. To protect laboratory personnel and ensure data integrity, pathologists must be familiar with the activities performed in their laboratories and the applicable regulatory and safety requirements. Failure to address issues proactively may result in exposure of personnel

Animal models are critical to the advancement of our knowledge of infectious disease pathogenesis, diagnostics, therapeutics, and prevention strategies. The use of animal models requires thoughtful consideration for their well-being, as infections can significantly impact the general health of an animal and impair their welfare. Application of the 3Rs-replacement, refinement, and reduction-to animal

In translational research, animal models are an important tool to aid in decision-making when taking potential therapies into human clinical trials. Recently, there have been a number of papers that have suggested limited concordance of preclinical animal experiments with subsequent human clinical experience. Assessments of preclinical animal studies have led to concerns about the reproducibility of

The 8th edition of the Guide for the Care and Use of Laboratory Animals (Guide) is clear in its requirement for each institution to establish and maintain an occupational health and safety (OHS) program as an essential part of the overall program of animal care and use. For over 30 years, AAALAC International has utilized a variety of methods to evaluate this component of OHS programs as part of the

Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant

For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because

Since its inception in the 1950s, hematopoietic cell transplantation (HCT) has become a highly effective clinical treatment for malignant and nonmalignant hematological disorders. This milestone in cancer therapy was only possible through decades of intensive research using murine and canine animal models that overcame what appeared in the early days to be insurmountable obstacles. Conditioning protocols

The procedures necessary to perform testing in a veterinary diagnostic laboratory have inherent associated risks to personnel in regard to exposure to infectious agents. In research institutions animals can be experimentally infected, acquire naturally occurring infections and can also be exposed to other hazards such as toxic chemicals or radiologic entities. A critical component of the use of animals

Development of new biomedical products necessitates nonclinical safety assessment in animals as a means of assessing potential risk to human patients. Pivotal nonclinical safety studies that support human clinical trials are performed according to Good Laboratory Practice (GLP) guidelines, which are designed to ensure that the study was conducted under carefully controlled conditions using standardized

Zoonoses, diseases transmitted between animals and humans, have been a concern in laboratory animal medicine for decades. Exposure to zoonotic organisms not only poses health risks to personnel and research animals but may also affect research integrity. Early laboratory animal programs were ineffective at excluding and preventing transmission of zoonotic diseases: the health status of the animals

Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized

Preclinical noninvasive imaging can be an indispensable tool for studying animal models of disease. In vivo imaging to assess anatomical, functional, and molecular features requires verification by a comparison to the macroscopic and microscopic morphological features, since all noninvasive in vivo imaging methods have much lower resolution than standard histopathology. Comprehensive pathological evaluation

For decades, histopathology with routine hematoxylin and eosin staining has been and remains the gold standard for reaching a morphologic diagnosis in tissue samples from humans and veterinary species. However, within the past decade, there has been exponential growth in advanced techniques for in situ tissue biomarker imaging that bridge the divide between anatomic and molecular pathology. It is now

Over 60% of NIH extramural funding involves animal models, and approximately 80% to 90% of these are mouse models of human disease. It is critical to translational research that animal models are accurately characterized and validated as models of human disease. Pathology analysis, including histopathology, is essential to animal model studies by providing morphologic context to in vivo, molecular

Failure to reproduce results from some scientific studies has raised awareness of the critical need for reproducibility in translational studies. Macroscopic and microscopic examination is a common approach to determine changes in tissues, but text descriptions and visual images have limitations for group comparisons. Semiquantitative scoring is a way of transforming qualitative tissue data into numerical

The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs' large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic,

Advancements in technology and digitization have ushered in novel ways of enhancing tissue-based research via digital microscopy and image analysis. Whole slide imaging scanners enable digitization of histology slides to be stored in virtual slide repositories and to be viewed via computers instead of microscopes. Easier and faster sharing of histologic images for teaching and consultation, improved

The need for international collaboration in rodent pathology has evolved since the 1970s and was initially driven by the new field of toxicologic pathology. First initiated by the World Health Organization's International Agency for Research on Cancer for rodents, it has evolved to include pathology of the major species (rats, mice, guinea pigs, nonhuman primates, pigs, dogs, fish, rabbits) used in

The use of agricultural animals in biomedical research is increasing. Their overall size and metabolic rate, organ size, longer gestation period, and other physiological similarities make them good candidates for animal models of human disease. There are a number of special considerations for use of traditional farm animals for biomedical research. Differences in physical plant infrastructure, handling

The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells

Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection

Aquatic vertebrates and cephalopods, amphibians, reptiles, and birds offer unique safety and occupational health challenges for laboratory animal personnel. This paper discusses environmental, handling, and zoonotic concerns associated with these species.