Research with captive wildlife in Animal Biosafety Level 2 (ABSL2) and 3 (ABSL3) facilities is becoming increasingly necessary as emerging and re-emerging diseases involving wildlife have increasing impacts on human, animal, and environmental health. Utilizing wildlife species in a research facility often requires outside the box thinking with specialized knowledge, practices, facilities, and equipment. The USGS National Wildlife Health Center (NWHC) houses an ABSL3 facility dedicated to understanding wildlife diseases and developing tools to mitigate their impacts on animal and human health. This review presents considerations for utilizing captive wildlife for infectious disease studies, including, husbandry, animal welfare, veterinary care, and biosafety. Examples are drawn from primary literature review and collective 40-year experience of the NWHC. Working with wildlife in ABSL2 and ABSL3 facilities differs from laboratory animals in that typical laboratory housing systems, husbandry practices, and biosafety practices are not designed for work with wildlife. This requires thoughtful adaptation of standard equipment and practices, invention of customized solutions and development of appropriate enrichment plans using the natural history of the species and the microbiological characteristics of introduced and native pathogens. Ultimately, this task requires critical risk assessment, understanding of the physical and psychological needs of diverse species, creativity, innovation, and flexibility. Finally, continual reassessment and improvement are imperative in this constantly changing specialty area of infectious disease and environmental hazard research.

Maximum-containment laboratories are a unique and essential component of the bioeconomy of the United States. These facilities play a critical role in the national infrastructure, supporting research on a select set of especially dangerous pathogens, as well as novel, emerging diseases. Understanding the ecology, biology, and pathology at the human-animal interface of zoonotic spillover events is fundamental to efficient control and elimination of disease. The use of animals as human surrogate models or as target-host models in research is an integral part of unraveling the interrelated components involved in these dynamic systems. These models can prove vitally important in determining both viral- and host-factors associated with virus transmission, providing invaluable information that can be developed into better risk mitigation strategies. In this article, we focus on the use of livestock in maximum-containment, biosafety level-4 agriculture (BSL-4Ag) research involving zoonotic, risk group 4 pathogens and we provide an overview of historical associated research and contributions. Livestock are most commonly used as target-host models in high-consequence, maximum-containment research and are routinely used to establish data to assist in risk assessments. This article highlights the importance of animal use, insights gained, and how this type of research is essential for protecting animal health, food security, and the agriculture economy, as well as human public health in the face of emerging zoonotic pathogens. The utilization of animal models in high-consequence pathogen research and continued expansion to include available species of agricultural importance is essential to deciphering the ecology of emerging and re-emerging infectious diseases, as well as for emergency response and mitigation preparedness.

Animals are valuable resources in biomedical research in investigations of biological processes, disease pathogenesis, therapeutic interventions, safety, toxicity, and carcinogenicity. Interpretation of data from animals requires knowledge not only of the processes or diseases (pathophysiology) under study but also recognition of spontaneous conditions and background lesions (pathology) that can influence or confound the study results. Species, strain/stock, sex, age, anatomy, physiology, spontaneous diseases (noninfectious and infectious), and neoplasia impact experimental results and interpretation as well as animal welfare. This review and the references selected aim to provide a pathology resource for researchers, pathologists, and veterinary personnel who strive to achieve research rigor and validity and must understand the spectrum of "normal" and expected conditions to accurately identify research-relevant experimental phenotypes as well as unusual illness, pathology, or other conditions that can compromise studies involving laboratory mice, rats, gerbils, guinea pigs, hamsters, naked mole rats, and rabbits.

In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein's receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K, and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface, are, however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, whereas Delta and "Delta Plus" lack a similar biomolecular basis to do so. This paper identifies 11 countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay, and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.

ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Evaluation Program (PEP), which focuses on microbial monitoring by and for laboratory animal diagnostic laboratories, and the Genetic Reference Monitoring Program (GENRef), which provides assay-ready reference DNA for genetic testing of mouse strains. Since 2008, PEP has grown to become a truly international program with participating laboratories in 5 continents. Launched in 2016, GENRef currently distributes DNA from 12 common inbred mouse strains for use in genetic monitoring of locally inbred colonies as well as for genetic testing of stocks, particularly genetically engineered stocks, of uncertain origins. GENRef has the capacity to include additional strains as well as additional species. PEP and GENRef provide the reagents at cost, as a resource to the international scientific community, in the interest of improving research quality in an environment of growing concern for research quality, rigor, and reproducibility.

The Institute for Laboratory Animal Research (ILAR) was created within the National Academies of Sciences, Engineering, and Medicine (National Academies) in 1953 when biomedical research using animals was in its infancy in terms of quantity, quality, complexity, sophistication, and care. Over the intervening 69 years, ILAR has witnessed unprecedented growth, followed by unprecedented decline, and then regrowth in usage of specific species and models and an overall shift in experimental burden away from larger to smaller species (ie, mice, fish, and rats). ILAR has contributed much to the evolution of necessary research using animals and animal models for the benefit of humans, animals, and the environment and to the development and implementation of humane principles and standards for care and use of research animals. ILAR has served as a "neutral broker" seeking consensus, solutions, common ground, and pathways forward for all professional constituencies engaged in conduct of animal research. In 2022, ILAR will become the Board on Animal Health Sciences, Conservation, and Research (BAHSCR) within the Division on Earth and Life Studies of the National Academies and the ILAR Journal will pause publication with volume 62. This manuscript recounts the history and accomplishments of ILAR 1953-2022, emphasizing the past 2 decades. The manuscript draws upon ILAR's communications and previously published histories to document ILAR's leaders, reports, publications, conferences, workshops, and roundtables using text, tables, references, and extensive supplemental tables. The authors' intention is to provide the scientific community with a single source document for ILAR, and they apologize for any omissions and errors.

The organization and function of the institutional animal care and use committee (IACUC) is the key component of government regulation and oversight of necessary scientific research using live animals and of AAALAC - International accreditation of animal care and use programs in the United States. The regulations, roles, and responsibilities of IACUCs have evolved since their inception 35 years ago from a limited focus on animal welfare and specific animal procedures to embracing scientific quality, data reproducibility and translation, and animal welfare as inextricably interdependent and critical components of generation of new scientific knowledge and medical treatments. A current challenge for IACUCs is in evaluating whether benefits to be derived (eg, new knowledge or treatments) justify any unavoidable pain, stress, or injury associated with proposed research protocols, because the former are long-term and at best speculative outcomes, whereas the latter are immediate and tangible for the study animals. Scientific consensus is that research most likely to generate significant new knowledge and medical treatments is that conducted to high scientific, technical, and quality standards and reported with full transparency to facilitate reproducibility. As an alternative to current benefits evaluations included in risk benefit and harm benefit constructs, the authors propose that IACUCs assess the proposed research for scientific quality and alignment of study elements with the study purpose (e.g., Fit for Purpose [FfP]), including justifications for study design components, selection of primary endpoints and technologies, rationale for data and statistical analyses, and research communication plans. Fit for Purpose endpoints are objective, immediate, and impactful as are the potential risks for study animals, and at the same time they are the best predictors for achievement of longer-term benefits. We propose that IACUCs and any revision of The ILAR Guide consider FfP concepts in place of traditional benefits assessment to accelerate the generation of new knowledge and treatments benefiting medical and veterinary patients and the environment through better science and animal welfare rather than to continue to rely on speculative future outcomes.

The Animal Care Panel is a nonprofit educational association of individuals and institutions concerned with the production, care, and study of laboratory animals. The entire United States and several foreign countries are represented in its membership. The Panel provides for the exchange of scientific information on all phases of laboratory animal care. It compiles and distributes information on films dealing with the handling of laboratory animals, and has initiated an animal technicians' training program. It publishes a bimonthly journal, "Laboratory Animal Care;" sponsors annual awards designed to encourage and reward outstanding accomplishment in the improvement of the care and quality of laboratory animals; and maintains close liaison with the Institute of Laboratory Resources (National Research Council), the American Veterinary Medical Association (through the American College of Laboratory Animal Medicine), the Laboratory Animal Breeders Association, and the National Society for Medical Research. Through its Animal Facilities Standards Committee, the Panel gathers and examines information that will aid in the establishment of high standards for the care of animals. The Guide for  Laboratory  Animal  Facilities and  Care was adopted by the Institute of Laboratory Animal Resources, National Academy of Sciences-National Research Council, on January 28, 1963.

In accordance with the «Aims of ICLA» (ICLA Bulletin No. 26, March 1970) the Governing Board established in 1969 a Working Party to prepare an International Nomenclature System for Outbred Animals. The members were: Professor, Dr. A. Spiegel, Federal Republic of Germany, chairman.Dr. M. Festing, United KingdomDr. K. Kondo, JapanDr. R. Loosli, SwitzerlandMr. S. Poiley, U.S.A. The nomenclature rules, completed and approved by the ICLA Governing Board on 8 December 1971, are published herewith. I am convinced that this system will bring order out of the existing chaos. The system is an offer to the world laboratory animal science, particularly the breeders and users. Editors of scientific journals, catalogues, and indices all over the world are also encouraged to require and use animal stock identification by this system for outbred animals used in experimentation. The ICLA Governing Board would have preferred to have seen an international centralization of symbol registration. However, the ICLA Secretariat has not got the capacity necessary for such a task and some practical solution to the registration problem will have to be found by the Governing Board. A final aim should then be for ICLA to publish a comprehensive world list of breeder symbols at intervals. Oslo, January 1972 Stian Erichsen  Secretary-General.

With the possible exception of inbred mice, the identification of laboratory animals has been in a state of anarchy until very recently. In a letter to the editor of LABORATORY ANIMAL CARE (19: 121-123, 1969), Mr. Samuel Poiley outlined the general principles of a system of nomenclature being developed by the Committee on Nomenclature of the ILAR. This journal requires that authors use standard terminology for rats and mice as listed in the ILAR publication ANIMALS FOR RESEARCH. We welcome the following report which represents a system of nomenclature for outbred animals and publish it as a service to the scientific community. Authors of papers submitted to this journal will be expected to identify their animals by this system. We urge the editors of other scientific publications to consider the merits of adopting standard terminology to end the reign of confusion in animal identification.

Clinical pathology testing for investigative or biomedical research and for preclinical toxicity and safety assessment in laboratory animals is a distinct specialty requiring an understanding of species specific and other influential variables on results and interpretation. This review of clinical pathology principles and testing recommendations in laboratory animal species aims to provide a useful resource for researchers, veterinary specialists, toxicologists, and clinical or anatomic pathologists.

Animal studies in pharmaceutical drug discovery are common in preclinical research for compound evaluation before progression into human clinical trials. However, high rates of drug development attrition have prompted concerns regarding animal models and their predictive translatability to the clinic. To improve the characterization and evaluation of animal models for their translational relevance, the authors developed a tool to transparently reflect key features of a model that may be considered in both the application of the model but also the likelihood of successful translation of the outcomes to human patients. In this publication, we describe the rationale for the development of the Animal Model Quality Assessment tool, the questions used for the animal model assessment, and a high-level scoring system for the purpose of defining predictive translatability. Finally, we provide an example of a completed Animal Model Quality Assessment for the adoptive T-cell transfer model of colitis as a mouse model to mimic inflammatory bowel disease in humans.

Laboratory registration codes, also known as laboratory codes or lab codes, are a key element in standardized laboratory animal and genetic nomenclature. As such they are critical to accurate scientific communication and to research reproducibility and integrity. The original committee on Mouse Genetic Nomenclature published nomenclature conventions for mice genetics in 1940, and then conventions for inbred strains in 1952. Unique designations were needed, and have been in use since the 1950s, for the sources of animals and substrains, for the laboratories that identified new alleles or mutations, and then for developers of transgenes and induced mutations. Current laboratory codes are typically a 2- to 4-letter acronym for an institution or an investigator. Unique codes are assigned from the International Laboratory Code Registry, which was developed and is maintained by ILAR in the National Academies (National Academies of Sciences Engineering and Medicine and previously National Academy of Sciences). As a resource for the global research community, the registry has been online since 1997. Since 2003 mouse and rat genetic and strain nomenclature rules have been reviewed and updated annually as a joint effort of the International Committee on Standardized Genetic Nomenclature for Mice and the Rat Genome and Nomenclature Committee. The current nomenclature conventions (particularly conventions for non-inbred animals) are applicable beyond rodents, although not widely adopted. Ongoing recognition, since at least the 1930s, of the research relevance of genetic backgrounds and origins of animals, and of spontaneous and induced genetic variants speaks to the need for broader application of standardized nomenclature for animals in research, particularly given the increasing numbers and complexities of genetically modified swine, nonhuman primates, fish, and other species.

Growing awareness of the ethical implications of neuroscience in the early years of the 21st century led to the emergence of the new academic field of "neuroethics," which studies the ethical implications of developments in the neurosciences. However, despite the acceleration and evolution of neuroscience research on nonhuman animals, the unique ethical issues connected with neuroscience research involving nonhuman animals remain underdiscussed. This is a significant oversight given the central place of animal models in neuroscience. To respond to these concerns, the Center for Neuroscience and Society and the Center for the Interaction of Animals and Society at the University of Pennsylvania hosted a workshop on the "Neuroethics of Animal Research" in Philadelphia, Pennsylvania. At the workshop, expert speakers and attendees discussed ethical issues arising from neuroscience research involving nonhuman animals, including the use of animal models in the study of pain and psychiatric conditions, animal brain-machine interfaces, animal-animal chimeras, cerebral organoids, and the relevance of neuroscience to debates about personhood. This paper highlights important emerging ethical issues based on the discussions at the workshop. This paper includes recommendations for research in the United States from the authors based on the discussions at the workshop, loosely following the format of the 2 Gray Matters reports on neuroethics published by the Presidential Commission for the Study of Bioethical Issues.

Researchers have worked with animals as models for decades to expand our knowledge of basic biological processes and to systematically study the physiology of disease. In general, the public has an expectation that work with animals has a purpose and will ultimately reap benefits. The likelihood of such an outcome is directly dependent on the quality of the science being conducted with those animals. However, not all frameworks for consideration of the ethics around animal research overtly consider scientific quality. In the following review, we explore the complex relationship between scientific quality and animal research ethics. We advocate for the development of a detailed "Harm-Yield Analysis" for the evaluation of biomedical animal research that emphasizes scientific quality along with societal benefit in the ethical justification of the research. We reflect on the lost opportunity to establish best practices in animal research early in the career of scientists by introducing in the curriculum and encouraging the use of a paradigm of the iterative consideration of the ethics of animal research alongside other aspects of experimental design.

We provide here a current overview of marmoset (Callithrix) evolution, hybridization, species biology, basic/biomedical research, and conservation initiatives. Composed of 2 subgroups, the aurita group (C aurita and C flaviceps) and the jacchus group (C geoffroyi, C jacchus, C kuhlii, and C penicillata), this relatively young primate radiation is endemic to the Brazilian Cerrado, Caatinga, and Atlantic Forest biomes. Significant impacts on Callithrix within these biomes resulting from anthropogenic activity include (1) population declines, particularly for the aurita group; (2) widespread geographic displacement, biological invasions, and range expansions of C jacchus and C penicillata; (3) anthropogenic hybridization; and (4) epizootic Yellow Fever and Zika viral outbreaks. A number of Brazilian legal and conservation initiatives are now in place to protect the threatened aurita group and increase research about them. Due to their small size and rapid life history, marmosets are prized biomedical models. As a result, there are increasingly sophisticated genomic Callithrix resources available and burgeoning marmoset functional, immuno-, and epigenomic research. In both the laboratory and the wild, marmosets have given us insight into cognition, social group dynamics, human disease, and pregnancy. Callithrix jacchus and C penicillata are emerging neotropical primate models for arbovirus disease, including Dengue and Zika. Wild marmoset populations are helping us understand sylvatic transmission and human spillover of Zika and Yellow Fever viruses. All of these factors are positioning marmosets as preeminent models to facilitate understanding of facets of evolution, hybridization, conservation, human disease, and emerging infectious diseases.