In 2008 ILAR convened a workshop that brought together 200 participants from 17 countries to identify and promote better understanding of important challenges in the conduct of animal research across country boundaries. These challenges include the sourcing of animals, the quality of veterinary care, competent staff, the provision of a suitable environment (including nutritious food and potable water) for animals, and ongoing oversight of the animal program, among others. This report summarizes the proceedings of the workshop, which has been a vital bridge for diverse colleagues and organizations around the world to advance initiatives to fill gaps in standards, professional qualifications, and coordination of animal use. ISBN 0-309-21502-1; 2011, 284 pages, 6 9, paperbound Chimpanzees in Research: Strategies for Their Ethical Care, Management, and Use Chimpanzees in biomedical and behavioral research constitute a national resource that has been valuable in addressing national health needs. However, the expected level of use of the chimpanzee model in biomedical research did not materialize, creating a complex problem that threatens both the availability of chimpanzees and the infrastructure required to ensure their well-being. This report examines the issues and makes recommendations.

Sepsis and trauma are both leading causes of death in the United States and represent major public health challenges. Murine models have largely been used in sepsis and trauma research to better understand the pathophysiological changes that occur after an insult and to develop potential life-saving therapeutic agents. Mice are favorable subjects for this type of research given the variety of readily available strains including inbred, outbred, and transgenic strains. In addition, they are relatively easy to maintain and have a high fecundity. However, pharmacological therapies demonstrating promise in preclinical mouse models of sepsis and trauma often fail to demonstrate similar efficacy in human clinical trials, prompting considerable criticism surrounding the capacity of murine models to recapitulate complex human diseases like sepsis and traumatic injury. Fundamental differences between the two species include, but are not limited to, the divergence of the transcriptomic response, the mismatch of temporal response patterns, differences in both innate and adaptive immunity, and heterogeneity within the human population in comparison to the homogeneity of highly inbred mouse strains. Given the ongoing controversy, this narrative review aims to not only highlight the historical importance of the mouse as an animal research model but also highlight the current benefits and limitations of the model as it pertains to sepsis and trauma. Lastly, this review will propose future directions that may promote further use of the model.

Human discovery of pharmacologically active substances is arguably the oldest of the biomedical sciences with origins >3500 years ago. Since ancient times, four major transformations have dramatically impacted pharmaceutical development, each driven by advances in scientific knowledge, technology, and/or regulation: (1) anesthesia, analgesia, and antisepsis; (2) medicinal chemistry; (3) regulatory toxicology; and (4) targeted drug discovery. Animal experimentation in pharmaceutical development is a modern phenomenon dating from the 20th century and enabling several of the four transformations. While each transformation resulted in more effective and/or safer pharmaceuticals, overall attrition, cycle time, cost, numbers of animals used, and low probability of success for new products remain concerns, and pharmaceutical development remains a very high risk business proposition. In this manuscript we review pharmaceutical development since ancient times, describe its coevolution with animal experimentation, and attempt to predict the characteristics of future transformations.

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic and nondomestic feline species. Infection in domestic cats leads to immune dysfunction via mechanisms similar to those caused by human immunodeficiency virus (HIV) and, as such, is a valuable natural animal model for acquired immunodeficiency syndrome (AIDS) in humans. An association between FIV and an increased incidence of neoplasia has long been recognized, with frequencies of up to 20% in FIV-positive cats recorded in some studies. This is similar to the rate of neoplasia seen in HIV-positive individuals, and in both species neoplasia typically requires several years to arise. The most frequently reported type of neoplasia associated with FIV infection is lymphoma. Here we review the possible mechanisms involved in FIV lymphomagenesis, including the possible involvement of coinfections, notably those with gamma-herpesviruses.

Avariety of infectious agents have been linked to cancer. Viruses, bacteria, and parasites have been linked to tumors in animals and humans. Viruses associated with cancer formation cause alteration of physiologic control of cell growth and proliferation or may increase the susceptibility of the host to other cancer risk factors such as environmental toxins. The study of virus–cell interactions has provided fundamental knowledge of cell biology and cell transformation. Viruses associated with cancer and model systems to study these mechanisms have established basic paradigms for virus–cell interactions and contributed greatly to the understanding of diseases associated with biomedically important viruses. More recently, some viruses, the so-called oncolytic viruses, have been used as agents against cancer. This background was the motivation and rationale for dedicating an entire issue of the ILAR Journal to models of virus-induced carcinogenesis and oncolytic viruses. The discovery of feline immunodeficiency virus (FIV) as a naturally occurring retrovirus, first in domestic cats and later in nondomestic feline species, allowed the comparative study of this lentivirus as a model of HIV-1 infection and disease. The ability to study the natural infection in feline species, which exhibit immune regulation similar to humans, has established this animal model as an important system to test hypotheses related to lentivirus disruption of immune control and subsequent pathologic outcomes. Sharing similar rates of neoplasia associated with both FIV and HIV infections, the comparative study of these viruses allow parallel studies to understand underlying factors that account for how lentivirusesmaypromote cancer formation. The review by Kaye and colleagues (2016) provides insights into current evidence on how FIV may promote the development of lymphoma in infected cats and the role of co-infections by other natural pathogens in tumor induction. Among these co-infections, the authors explore the role of feline gamma-herpes virus as a contributing factor to disease in infected cats and in retrovirus latency. The authors detail in their article the need for further evaluation of unique genetic elements of these viral pathogens and the influence of co-infections in disease outcomes. In addition, the authors discuss unique opportunities to use naturally infected animal populations from geographically disperse regions to test hypotheses around lentivirus-associated carcinogenesis. One of the earliest viruses associated with cancer was mouse mammary tumor virus (MMTV), which has served as a model of retroviral transmission and in investigations seeking to understand how the antiviral immune response influences the incidence of cancer. The review in this issue by Dudley and colleagues (2016) outlines some of the lessons learned from MMTV. It includes recent studies that have determined the interplay between key target cells and the immune system that characterizes the infection and pathogenic outcomes. Unique mechanisms of immune evasion are used by MMTV to allow for viral transmission and ultimately cellular oncogene expression. This model system has provided fundamental knowledge of how oncogenes disrupt cellular growth and continues to shed light on how retroviruses evade immune elimination. Also, in this issue, rodentmodels to evaluate oncolytic viruses as therapeutic agents are reviewed by Speranza and colleagues (2016). The use of viruses as anticancer agents has been evaluated in clinical trials in humans for more than 20 years and oncolytic viruses have emerged as viable therapeutic agents over the past decade. This review compares the range of viruses used as therapeutic agents and the evidence for those that are most promising. The review illustrates rodentmodels used to evaluate the preclinical efficacy of oncolytic viruses in context to the intrinsic ways these agents target cancer cells and achieve antitumor effects. The recent documentation of a successful phase III