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3
Setting and Implementing an Agenda for Veterinary Research

Modern veterinary research has markedly improved the quality of life of animals and humans, as indicated by numerous historical achievements. The demands on veterinary research have not diminished but rather have increased, with such emerging threats as bioterrorism and emerging infectious diseases. As shown by the critical research issues outlined in the previous chapter, veterinary and comparative medicine research is becoming a more pressing need than ever before. The ability of veterinary researchers to address the threats of animal disease and to meet societal needs depends largely on the nation’s research capacity. Because research resources are finite, it is important to set a research agenda that will address high-priority issues and anticipate future needs and that can be executed effectively.

In this chapter, the committee attempts to set a research agenda for veterinary research related to public health and food safety, comparative medicine, and animal health and welfare. Examples of critical research needs in each of the disciplines are given in Chapter 2 (which appear in a box at the beginning of each subsection in this chapter). The committee then identifies the short-, intermediate, and long-term research that must be done in order to address the selected critical issues. The committee also assesses the expertise and some of the major infrastructure needed, suggests some possible strategies to achieve the research agenda, and discusses the current sources of funding for the research.

In devising strategies to achieve the agenda for different elements of veterinary research, the committee has noticed that there are overarching strategies that are applicable to most, if not all, of the disciplines in veterinary science discussed



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Critical Needs for Research in Veterinary Science 3 Setting and Implementing an Agenda for Veterinary Research Modern veterinary research has markedly improved the quality of life of animals and humans, as indicated by numerous historical achievements. The demands on veterinary research have not diminished but rather have increased, with such emerging threats as bioterrorism and emerging infectious diseases. As shown by the critical research issues outlined in the previous chapter, veterinary and comparative medicine research is becoming a more pressing need than ever before. The ability of veterinary researchers to address the threats of animal disease and to meet societal needs depends largely on the nation’s research capacity. Because research resources are finite, it is important to set a research agenda that will address high-priority issues and anticipate future needs and that can be executed effectively. In this chapter, the committee attempts to set a research agenda for veterinary research related to public health and food safety, comparative medicine, and animal health and welfare. Examples of critical research needs in each of the disciplines are given in Chapter 2 (which appear in a box at the beginning of each subsection in this chapter). The committee then identifies the short-, intermediate, and long-term research that must be done in order to address the selected critical issues. The committee also assesses the expertise and some of the major infrastructure needed, suggests some possible strategies to achieve the research agenda, and discusses the current sources of funding for the research. In devising strategies to achieve the agenda for different elements of veterinary research, the committee has noticed that there are overarching strategies that are applicable to most, if not all, of the disciplines in veterinary science discussed

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Critical Needs for Research in Veterinary Science in this report. The especially compelling scientific opportunities to improve quality of life and minimize threats include the following: Implementation of the concepts of one medicine and interdisciplinary research in the broader biomedical research agenda. Substantially improve the integration of molecular biology, genomics, immunology, whole-animal physiology, pathophysiology, and other disciplines in disease research. Encourage scientists, through grant mechanisms and other means, to work collaboratively across disciplines, institutions, and agencies. Encourage research institutions to foster an environment that nurtures and rewards successful team-oriented investigators and research. Expand veterinary-student involvement in ecosystem health and the ability to work collaboratively to study and understand complex systems and the intricate relationships between human beings (individuals, cultures, and societies), animals (domestic and wild), and the environment. Setting of priorities research to expand our knowledge, detection, and control of infectious diseases. Emphasize classes of disease agents that have the highest economic importance, including those most likely to cause massive epizootics or epidemics, new and emerging diseases, and candidate bioterrorism agents. Emphasize the eradication of laboratory animal diseases that adversely affect the quality of biomedical data. Focus on understanding the molecular bases of virulence and how pathogenic organisms replicate and survive in the environment including studies of vector biology, wild animal hosts and reservoirs, host defense factors, and host-pathogen interactions. Develop and validate rapid, sensitive, reliable, and, where possible, quantitative systems for detecting and monitoring disease-causing organisms. Expansion of the study and use of bioinformatics and development of databases and other resources that are readily accessible to the scientific community to enable A population-level view of disease and research on interactions between wildlife, domestic animals, and humans. Tracking of pathogen prevalence in animals, including companion, food-producing, and laboratory animals. Tracking of foodborne diseases. Maximizing of the sharing and efficiency of developing, preserving, and housing important rodent and other animal models. Quantification of critical, scientifically based animal health and welfare characteristics to optimize sustainable and socially responsible food-animal production and laboratory animal research. Expansion of research on the human-animal bond and the overall role of animals in society.

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Critical Needs for Research in Veterinary Science PUBLIC HEALTH AND FOOD SAFETY Food Safety Examples of Critical Research Needs Rapid, sensitive, and accurate assays for detecting foodborne pathogens. Epidemiological approaches to identifying risk factors and intervention strategies that have the greatest effect on reducing foodborne pathogens and antimicrobial-resistant microorganisms associated with livestock, poultry, and aquaculture. This includes a more comprehensive understanding of the epidemiology and genetic elements of the foodborne zoonotic agents, especially of those agents that have recently emerged. Practical and effective interventions for minimizing carriage of and contamination with food-associated pathogens of animal origin. Methods to assess the safety and nutritional value of transgenic and cloned food-producing animals. Identification of previously unrecognized foodborne pathogens of animal origin. Research Agenda Immediate Priorities A critical factor in reducing animal-associated foodborne illnesses is the ability to detect and isolate the responsible agents. A high priority for the near term is to develop rapid, sensitive, and accurate assays for detecting foodborne pathogens in feces and meat and on animal surfaces. Most highly sensitive microbiological assays for detecting pathogens in meat and feces take days to complete. Real-time, easy-to-perform assays are needed to enable point-of-contamination detection and monitoring so that corrective actions can be taken promptly to reduce pathogen dissemination. The more quickly interventions can be implemented at critical points of contamination, the more effective pathogen control strategies will be in reducing foodborne illness. Functional genomics presents an additional research opportunity. Knowledge of a microorganism’s genome can be used to determine the functions of genes and their products and may be useful for developing real-time assays that not only detect pathogens but also predict their pathogenicity, identify novel pathogenic mechanisms, and trace pathogens to their sources. Identifying in animals virulence-associated genes in commensal microorganisms that are patho-

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Critical Needs for Research in Veterinary Science genic to humans may lead to recognition of pathogens heretofore believed to be innocuous. Mid-term Priorities Foodborne illnesses are caused by a complex interaction of factors in the path from farm to consumption. Most foodborne disease cases are preventable, and there is a need to develop a more science- and risk-based food-safety system that will enable the best allocation of resources to provide a continuous, effective reduction in the incidence of foodborne illnesses. Practical and effective food-safety interventions need to be developed to reduce human illnesses. Mathematical models can be used to identify the most critical sites along the food chain where pathogen reduction would have the greatest impact. Mathematical modeling and risk assessment are needed to identify intervention points or strategies that will be most useful in reducing foodborne pathogens and antimicrobial-resistant microorganisms associated with animals used in food production. To apply the models, we need to obtain fundamental data through an integrative approach involving epidemiology, clinical and laboratory studies, and surveillance to identify how pathogens enter the farm environment, how they persist and spread in that environment, and what dosage causes disease in humans. In addition, a systematic elucidation of the ecology of antimicrobial-resistant microorganisms associated with animals and the farm environment is needed and will be instrumental in development of a risk model that ranks the modes of acquisition of antimicrobial resistance among pathogens of public health significance. Moreover, if the model is used as a guide, the most effective intervention strategies for reducing the prevalence of antimicrobial-resistant microorganisms may be identified. Many procedures are available for reducing pathogen contamination on the farm, but several have not been suitably validated. Controlled studies are needed to evaluate the procedures, and research is needed to develop more effective and practical intervention strategies for controlling pathogens in production and slaughter environments. Long-term Priorities Tens of millions of food-associated cases of acute gastroenteritis are caused by agents of unknown etiology each year in the United States. If we identify the responsible agents, research can be focused on developing effective detection and intervention strategies to reduce their occurrence in the food chain. A multi-targeted research approach is needed to reveal and characterize these yet-to-be discovered harmful microorganisms. Studies are needed to elucidate the roles of environmental and other exogenous factors in the emergence of newly evolved pathogens. Examples of such

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Critical Needs for Research in Veterinary Science factors are the introduction of new antibiotics, changes in production practices, and climate changes, all of which may provide conditions that influence genetic modification and selection and enable microorganisms to compete better under new, more stressful conditions. The development of transgenic and cloned animals is impeded by concerns about the safety and nutritional value of the foods they produce. Validated methods are needed to assess the potential acquisition of toxins, allergens, undesirable endocrine activity, and other adverse properties that may result from genetic manipulation. Strategies to Achieve Research Research on foodborne illnesses requires biocontainment facilities, development of and access to databases and pathogen banks, and expertise in animal microbiology, mathematical modeling, genomics, and immunology. Veterinary researchers should apply modern technologies to detection of pathogens in feces and foods of animal origin. Genomic and immunological research on foodborne pathogens would speed up the development of rapid detection. Such research requires access to properly equipped laboratories, genomic and sequence data, and banks of well-characterized reference microorganisms. In addition, research on methods for assessing the safety and nutritional value of transgenic and cloned animals requires an interdisciplinary approach involving toxicologists, nutritionists, biochemists, microbiologists, and veterinary scientists to develop a set of well-documented protocols and assays for risk assessment of foods from genetically altered animals. Development of mathematical models to identify intervention points could begin with integrating animal and environmental surveillance systems into established human surveillance systems. Pathogen-prevalence and food-attribution databases should be developed and should be readily accessible to all. Once the models are developed, they can be applied to determine the most effective on-farm intervention strategies for reducing human illnesses attributed to animal-associated foodborne pathogens. Development of practical on-farm interventions requires the application of genomics, proteomics, sequencing, and genetic modification to the elucidation of foodborne-pathogen colonization of animals and the application of innovative vaccines, competitive microorganisms, phage, antimicrobials, diet modification, and genetic modification of animals to the reduction of pathogen carriage by animals. Veterinary researchers should collaborate with food microbiologists, statisticians, and nonveterinary scientists to strengthen and advance food-safety research. Collaboration with federal agencies engaged in food safety issues—such as Food and Drug Administration (FDA), the US Department of Agriculture (USDA) Food Safety and Inspection Service and Animal and Plant Health Inspection Service, and the Centers for Disease Control and Prevention (CDC)—would also be beneficial.

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Critical Needs for Research in Veterinary Science Funding Sources Funding for veterinary-science-related food-safety research has been available through the USDA National Research Initiative (NRI), the USDA Cooperative State Research, Education, and Extension Service (CSREES) National Integrated Food Safety Initiative, the USDA Agricultural Research Service (ARS), the FDA Center for Food Safety and Applied Nutrition, the FDA Center for Veterinary Medicine, the National Institutes of Health (NIH), the Department of Homeland Security (DHS), and veterinary pharmaceutical companies. However, research on the safety of food products from transgenic and cloned animals does not have an identifiable funding source, because most programs address food safety in relation to pathogens. Biosecurity Examples of Critical Research Needs Improved ability to detect and identify disease and pathogens in animal populations. Improved ability to detect pathogens and toxicants in food along the processing chain. Improved understanding of interactions between pathogens and hosts so that effective preventive measures and countermeasures can be developed. Rational development of cost-effective countermeasures, both vaccines and nonspecific therapeutic agents. Research Agenda Immediate Priorities The most important factor in limiting the impact of any disease outbreak—natural or human-made, preharvest or postharvest—is quick identification. Accurate clinical recognition and differential diagnosis should have high priority for research in the short term to make rapid response and eradication or containment possible. The need for diagnostics research is discussed in detail in another National Research Council report Animal Health at the Crossroads (NRC, 2005). We must develop technical means of either securing food products physically or identifying the presence of adulterants before they can be consumed in the food of humans or animals. Species-neutral disease surveillance should be adopted as the norm and continually improved; it will entail bringing together information from all health-care providers and agricultural professionals to discover disease wherever it originates

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Critical Needs for Research in Veterinary Science rather than waiting until disease occurs in humans. In light of today’s increased communication and travel, this species-neutral disease monitoring should be international, and there should be broad and open datasharing. Understanding how to control an outbreak will be facilitated by the use of disease-specific mathematical risk-assessment models for prediction of outbreak dynamics. Mid-term Priorities A better understanding of how to stimulate acquired immunity in large populations of livestock (for example, by vaccination) is imperative. Because of its potential unprecedented impact, foot-and-mouth disease should be at the top of the list of research priorities. New methods of antigen presentation and effective adjuvants are needed for animal immunization. Ideally, the nation should be capable of producing animal vaccines rapidly with the latest techniques in the event of an outbreak. Research on vaccines will also be applicable to human health. Long-term Priorities We are little beyond the era of using “blunt” immunological tools as medical countermeasures; improving this situation dramatically may require 20-30 years of human and veterinary research. Improving our understanding of the complex interplay of antigens, virulence factors of potential threat agents, and immunological responses in animals and humans should have high priority for veterinary research in biosecurity. A better understanding of the extreme complexity of the immune system in humans and animals would enable us to exploit its protective effects without inadvertently causing harm. Long-term research should also emphasize how to detect and interpret host responses to disease agents better. That would allow us to make earlier diagnoses—even before the onset of clinical illness—and to exploit innate immunity (nonspecific protection from disease) and other resistance mechanisms in target species. Strategies to Achieve Research Agenda An improved understanding of the pathogens that affect biosecurity will require application of genomics, proteomics, sequencing, and transgenic technologies. The critical infrastructure for such research will include biocontainment laboratories and animal housing facilities that are now being planned or under construction; access to genome and sequence data and antibody, nucleic acid, and protein arrays to help us understand the immune system; and banks of well-characterized reference agents and reagents. As we wage the war on terrorism and emerging infectious diseases, critical subspecialties of veterinary medicine

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Critical Needs for Research in Veterinary Science will include infectious disease, immunology, epidemiology, food safety, agricultural economics, and public health. An absolute necessity for the most rapid progress will be the formation of interdisciplinary teams of other medical specialties working across scientific, geographic, and national borders. One example of a strategy for training personnel in biosecurity research is the incorporation of food-security concepts into food-safety curricula; similarly, we must leverage educational programs targeting naturally occurring disease to deal with intentional outbreaks. Moreover, cross-disciplinary training, such as exposing veterinary students or researchers to human medical training and faculties and vice versa, will prove to be beneficial over the long term. Finally, we must constantly seek to discover, understand, and respond to disease by agent, not by species, and seek to enhance awareness, communication, and understanding internationally. Funding Sources The needed research regarding diagnostics and identification and pathogenesis of threat agents was traditionally funded only by the Department of Defense. Since 2003, DHS and, to some extent, USDA have supported the diagnostic work, and NIH the fundamental pathogenesis and immunological research, at least in humans and nonfood-animal species. Much less funding is available to do similar work on foreign animal diseases that do not directly affect humans but could devastate our roughly $160 billion livestock economy. ANIMAL HEALTH AND WELFARE Food-Producing Animals Examples of Critical Research Development of capacity and implementation of broad programs in comparative medicine to understand, rapidly detect, and control zoonotic and nonzoonotic diseases in food-producing animals raised in concentrated production units, with emphasis on techniques and technologies for field use in large-animal populations. Evaluation of the implications of increases in productivity achieved through genetic or pharmaceutical means for animal health, nutrient, and metabolic requirements. Monitor and assess trans-species disease transmission, epidemiology, and the delineation of resistance, susceptibility, and virulence factors across animals and pathogenic organisms.

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Critical Needs for Research in Veterinary Science Research Agenda Immediate Priorities The increasing tendency to concentrate food animals in large production units that require complex distribution and societal interaction suggests that the most critical veterinary-science research goals associated with food animals are to develop and implement capacities and broad programs in comparative medicine to understand, detect, and control endemic and emerging diseases. High priority should be given to Development of rapid, accurate field-applied systems for detection of endemic and zoonotic diseases of food animals to prevent unnecessary quarantine, slaughter, and indemnification. Development and deployment of appropriate and safe techniques to control diagnosed critical food-animal diseases (for example, foot-and-mouth disease). Determination, evaluation, and quantification of critical, measurable environmental conditions and physiological stress and welfare (including nutritional) characteristics in food animals that affect health, well-being, and productive performance. That should include measurement of the effect of genetic selection or metabolic modifiers (such as bovine somatotropin and porcine somatotropin) on focused and increased performance. Mid-term Priorities Although our ability to detect, respond to, and recover from disease outbreaks in food-producing animals is important, prevention of diseases is even more desirable. Research should aim to develop effective measures to prevent critical and economically important diseases of food animals. Research is also needed to develop and facilitate delivery systems for rapid immunization of food animals. Long-term Priorities Great progress is being made in the determination of the genome of each species of food animal, and the process will probably be completed far sooner than originally expected. The mapped genomes enable correlation between components of the genome with resistance to and avoidance of diseases. That and other new knowledge should be incorporated to develop, isolate, and deploy resistance to critical endemic and economically important diseases. Strategies to Achieve Research Agenda The implementation of appropriate management systems with reduction in excessive quarantine and indemnification practices would have enormous eco-

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Critical Needs for Research in Veterinary Science nomic implications and would require significant investment in facilities and personnel trained to undertake the necessary investigations. Because some of the diseases of food-producing animals are highly pathogenic, biosafety level 3-agriculture laboratories are necessary for some of the research. The research community could benefit from an inventory of its capacity for research on diagnostics and on development and production of preventives (such as vaccines) against priority-identified zoonotic diseases. Studies on genetic resistance to zoonotic diseases in food animals are needed and they could be initiated on the basis of emerging understanding of the genome of each food-animal species. Thus, veterinary researchers could benefit from an inventory of all relevant research in food-animal species and in nonfood-animal species that has transferability to food-animal species. Research on critical factors that affect the health and welfare of food-producing animals (such as the environment, genetic selection to enhance performance, or pharmaceutical manipulation of metabolism on the physiological response to stress) has been limited. Morbidity and mortality associated with plant toxicities in grazing animals continue to be a problem in many parts of the country. There is an immediate need for an organized effort in this area, which will require investment in trained personnel, organization of appropriate facilities, and assembly of appropriate teams of scientists with veterinary and animal science training. Priority for this work must be made by appropriate funding agencies, and a national coordination is needed to establish the necessary cooperation, collaboration, and personnel training. Until this effort is made, animal agriculture will remain unable to address adequately and respond to questions of the welfare impacts associated with commercial food-animal production practices. Funding Sources USDA provides some funds through such initiatives as the animal health funds administered through CSREES, the NRI and formula funds to the land grant universities and colleges of veterinary medicine. In many cases, the funds are split between the animal-production research departments in colleges of agriculture and veterinary colleges. Funds given by USDA for basic research, such as NRI, are available for health-related work, but the evaluation and administrative process may not have adequate representation or expertise to offer balanced and unbiased review of proposals. USDA funds in-house basic and translation food-animal health research through ARS. As in human medicine, some funding opportunities for clinical research on food animals are provided by private industry (pharmaceutical, animal-health and so on). However, that source funds individual projects and is not adequate to build a sustainable and unbiased research program.

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Critical Needs for Research in Veterinary Science Aquaculture Examples of Critical Research Needs Improved understanding of immune responses (especially cell-mediated) in fish to facilitate the development of effective vaccines and appropriate delivery systems. Improved methods of pathogen detection. Increased effectiveness and safety of medications used to treat diseases in aquaculture species. Enhanced understanding of the impact of aquatic animal production systems on marine and freshwater ecosystems. Research Agenda The primary role of veterinary researchers in aquaculture is the prevention, control, and treatment of diseases. Intensive farming of aquatic species facilitates the spread of diseases in a population. A thorough understanding of the host, infectious agents, and environment is critical to the design of management practices and therapeutic interventions that optimize health and minimize environmental impact. Challenges in this field include inadequate understanding of the physiology of many farmed aquatic species, as opposed to mammals; of how varying body temperatures affect disease processes and responses to therapeutic interventions and vaccines; and of the environmental effects of farming practices, medications, and transgenic species. Immediate Priorities High priority should be given to developing accurate and cost-effective diagnostic tests to allow rapid treatment and prevent spread of diseases. Therapeutic agents should be developed and tested for efficacy. FDA recognizes that there are several aquatic-animal diseases for which no drugs have been approved (FDA, 2003). It is estimated that 10% of production (about $71.4 of 714 million in finfish aquaculture in 2000) is lost each year because of parasites and other infectious disease (USDA-ARS, 2004a). Studies to develop effective countermeasures should be conducted immediately for control of diseases in aquatic animals to minimize risks to food safety and the environment (Haskell et al., 2004) and to reduce economic losses.

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Critical Needs for Research in Veterinary Science COMPARATIVE MEDICINE Examples of Critical Research Needs Advanced training of comparative-medicine scientists to support and facilitate biomedical research, with emphasis on expertise in phenotype and behavior assessment of unique rodent strains. Further development and refinement of animal models to advance biomedical research. Expansion of resources and methods for characterizing the genetic background, phenotype, and behavior of unique mouse and rat strains. Enhanced methods for preserving valuable models and improving the reproductive efficiency of laboratory animals. Improved methods for genetic engineering in laboratory animal species other than the mouse to advance understanding of select diseases. Research Agenda Immediate Priorities Increasing the number of comparative-medicine scientists to meet the demand for interdisciplinary and translational research should have high priority. Translational research aims to move basic-biology research from the bench to applications for patient care. Biomedical research has evolved to become more interdisciplinary; research is conducted by teams or individuals with backgrounds in two or more scientific disciplines. Veterinarians with training in biomedical research provide an invaluable perspective that is necessary for the advancement of interdisciplinary and translational research. Comparative-medicine veterinarians provide critical research, expertise, and advice in animal modeling and experimental design. Furthermore, as the genetically engineered mouse has become a vital tool for advancing biomedical research in this genomics era, there is an increased demand for phenotype and behavior analysis of these unique strains. Highly trained comparative-medicine veterinarians and scientists are critical for scientific analysis of such unique strains and will have an important influence on the advancement of biomedical research as a whole. Another effort that warrants high priority is improvement in our understanding of factors that affect the phenotype behavior of unique mouse and rat stains. The phenotype of the genetically engineered mouse can be seriously affected by environmental factors and modifier genes (Nadeau, 2001), but mutations have different phenotypes on different mouse-strain backgrounds (Abeliovich et al., 1993; Smithies and Maeda, 1995; Threadgill et al., 1995). Better understanding is

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Critical Needs for Research in Veterinary Science needed to characterize effects of the modifier genes and environment on mutant mouse phenotypes. Mid-term Priorities Efficient methods for preserving important rodent strains are needed to maximize the efficiency of laboratory animal housing resources. For example, because of strain phenotype effects, mutant mouse strains are increasingly bred into different mouse-strain backgrounds to uncover phenotypes of the mutations being studied. However, cryopreservation technologies are not consistently well developed in rodent species. Further technological advances with in vitro fertilization techniques that use a frozen sperm from mice and rats are needed. In addition, advances in cryopreservation techniques for rodent and other animal models are needed and would benefit the veterinary research enterprise. Long-term Priorities Advances in genetic-engineering technologies in laboratory animal species besides the mouse would be valuable in advancing biomedical research in many respects. However, the technological efficiencies of generating genetically engineered mice have not been easily transferable to other laboratory animal species. For example, fertilized ovum collection, microinjection, and implantation procedures are not nearly as efficient in other species, and that precludes the generation of large numbers of these transgenic animals. Research to develop and use embryonic stem cells to generate “knockout” animals of other species should be expanded. Rapid and streamlined approaches to the transfer of mutations and genomic segments from one strain background to another would foster rapid progress. Strategies to Achieve Research Agenda The shortage of veterinary scientists in comparative medicine must be addressed by establishing mechanisms to train additional veterinarians in biomedical research. Veterinary curricula should emphasize research during undergraduate and graduate animal science and veterinary education. Colleges of veterinary medicine should encourage mentoring to give research faculty the opportunity to serve as role models to interest students in careers in comparative-medicine research. Additional programs are needed to provide postdoctoral training of veterinarians in comparative medicine in molecular and cell biology and to characterize the large number of naturally occurring and induced animal models, including rodents. More institutions should develop phenotype and behavior-assessment cores to facilitate analysis and characterization of unique rodent strains generated. Funding to improve efficient methods for the preservation of unique models will lead to substantial reductions in costs associated with animal research. Finally,

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Critical Needs for Research in Veterinary Science improved methods for developing genetically engineered animals of other laboratory animal species could be used to advance understanding of select diseases. Funding Sources The NIH National Center for Research Resources (NCRR) provides grant support to advance the training of comparative-medicine scientists to support and facilitate the biomedical research enterprise. Some awards, such as the K26 midcareer Investigator Awards in Mouse Pathobiology Research, are designed specifically to provide research training in phenotype and behavior assessment; other awards, such as the K01 and F32 individual awards and the T32 Institutional Research Training Grants, are designed to train veterinarians in biomedical fields in comparative medicine or comparative pathology. Those are successful programs, but the number of awards falls short of the current demand. NCRR also has R13 (Investigator-Initiated Conference Grants) and U13 (Conference Cooperative Agreements) awards to support scientific meetings. There is insufficient funding for studies focused on developing efficient methods for preserving important laboratory animal strains or on advancing genetic-engineering technologies for other laboratory animal species. Small awards in those fields may be made by grant foundations, such as the American College of Laboratory Animal Medicine Foundation. NCRR has a mutant-mouse regional resource centers program that supports centers that provide induced mutant-mouse lines to investigators. EMERGING ISSUES IN VETERINARY SCIENCE Emerging Infectious Diseases Examples of Critical Research Needs A preemptive approach to predict and prevent infectious diseases. New tools to identify novel, potentially zoonotic pathogens in wildlife populations that may be the next HIV/AIDS or SARS coronavirus. Such tools will include microarrays and other sophisticated biotechnological applications based on the pool of known zoonotic EIDs that wildlife populations harbor. Increased involvement of veterinary researchers in understanding the wildlife trade as a mechanism of EID introduction and in understanding how zoonotic bioterrorism agents may behave if released in the United States. The causes, anthropogenic, ecological and environmental drivers, and effects of emerging diseases of livestock and wildlife.

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Critical Needs for Research in Veterinary Science Research Agenda Emerging diseases are often associated with substantial human mortality and morbidity. Research is required to achieve a predictive, preemptive approach to EID research. National strategies to deal with the EID threat should focus on predicting the risk of EIDs and developing strategies to alleviate the risk (for example, preventing underlying causes, such as trade in wildlife and high-risk wildlife-human interaction). Models for the predictive approach include a number of projects supported through the NSF-NIH ecology-of-infectious-diseases initiative (NIH, 2002) and a recent study of the risk of non-SIV retrovirus emergence in bush-meat hunters in Cameroon (Wolfe et al.,2004). Immediate Priorities To deal with EIDs early during their emergence, diagnostics and rapid screening capacity are required on a global scale that would avoid excessive depopulation in areas of outbreaks. Tools for pathogen discovery have to be integrated into a predictive risk assessment. Surveillance of potential wildlife reservoirs for unknown, potentially zoonotic agents is possible with such molecular tools as microarrays, nucleic acid detection technology (including novel chip technology), and reverse transcription-polymerase chain reaction. Those approaches should be used in areas that are hot spots for EIDs and on wildlife reservoirs known to harbor other zoonotic agents. Research is needed to assess how environmental and ecological drivers of EIDs cause changes in pathogen dynamics between and within populations and allow diseases to emerge. Mid-term Priorities There has been a great deal of concern about a number of potential bioterrorism agents, some of which are relatively newly emerged pathogens. Little is known about how such agents as Rift Valley fever, if artificially released in the United States, might persist in wildlife populations and present a continued threat to public health. Research is needed on the role that livestock and native wildlife will play in allowing released bioterrorism agents to become endemic in the United States and cause long-term problems (Box 3-2). Long-term Priorities Long-term and on-going research should aim to improve our understanding of the biology and ecology of infectious diseases in wildlife, domestic animals, and other reservoirs. Such knowledge would help in the development of timely responses to and countermeasures against disease emergence and in the rapid identification of emerging agents. Research on the causes of EIDs is required to

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Critical Needs for Research in Veterinary Science BOX 3-2 Example of an Interdisciplinary Research Approach to Studying Diseases—Rift Valley Fever Rift Valley fever (RVF) is a mosquito-borne viral disease whose cyclic epidemics since the 1930s have had devastating economic effects on livestock populations throughout much of sub-Sahara Africa. Although the virus was not initially thought to be lethal to humans, an epidemic in East Africa in 1997-1998 resulted in the death of several hundred people. Research with laboratory rats in the early 1980s clearly established that a single gene in LEW inbred strains conveyed resistance to the RVF virus. Anderson et al. (1987) constructed a congenic strain in which the LEW resistance gene was backcrossed onto a susceptible WF inbred strain. Identification of the gene and its variation in resistant and susceptible strains would be a major step in production of resistant livestock or development of effective vaccines for both livestock and humans. Rat-genetics resources were not available in the 1980s to identify and clone the gene, and funding agencies were not sufficiently interested in RVF to sustain the research initiated by those and other scientists. September 11, 2001, changed our collective thinking about the importance of research on RVF. The disease has been identified as one of many with potential for use in agricultural bioterrorism and is also one of the high-priority diseases identified for attention by the Food and Agriculture Organization’s Emergency Prevention System (http://www.fao.org/). The implementation of two very important biotechnologies will permit current science to exploit the valuable rat strain developed by Anderson et al. Although resources were not available to maintain the congenic strain as a breeding colony, the scientists and the NIH Division of Veterinary Resources (http://www.ors.od.nih.gov/dirs/vrp/ratcenter/) had the foresight to preserve the congenic strain as frozen embryos. A rat genome project has generated a complete sequence of the rat genome and maps of several thousand markers (http://rgd.mcw.edu/about.shtml), which will permit scientists to identify the LEW region in the congenic strain and to identify the specific genetic difference between resistant and susceptible rats. Rederivation of the cryopreserved colony is under way as this report is being written, and a map- and sequence-based strategy to identify and clone the gene is being funded by the Department of Homeland Security. This work is possible only because the disciplines of epidemiolgy, virology, and mammalian genetics were tied to twenty-first-century genomics through embryology and cryobiology. understand how such factors as trade, encroachment into wildlife habitat, unnatural mixing of species, hunting, and overpopulation affect pathogen dynamics in animals and cause emerging diseases in humans. Research is needed to develop control strategies, drug candidates, and other therapies for key emerging diseases for which few therapies exist, for example, hemorrhagic fevers; encephalitides,

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Critical Needs for Research in Veterinary Science such as Nipah virus disease; and now-endemic emerging diseases, such as West Nile virus fever and hantavirus pulmonary syndrome. Strategies to Achieve Research Agenda EID research is multidisciplinary, because these diseases are almost always linked to an ecological factor (such as populations of wildlife reservoirs that migrate or change in patterns seasonally) or to a physical environmental factor (such as climate or pollution) (NRC 2003b). Teams of researchers that include veterinarians, wildlife biologists, geographers, mathematical modelers of disease dynamics, and ecologists have been particularly successful in investigating new EIDs (such as SARS, Nipah virus disease, West Nile virus fever, and highly pathogenic avian influenza) and in dealing with outbreaks of disease once they have emerged in human, domestic animal, or wildlife populations. For example, West Nile virus fever is a disease primarily of avian hosts that spills over into mammalian species, most of which are dead-end hosts for the virus (including humans). Understanding its spread and predicting its effects will require collaboration among vector biologists, climatologists, microbiologists, veterinary researchers, ecologists, and modelers. Increased collaboration among veterinary researchers working at federal agencies—such as DHS, FWS, and USDA—will allow them to study the role of international wildlife trade in disease introduction and the potential dissemination of bioterrorism agents in wildlife populations. Veterinary medical curricula should be adjusted to reflect the growing demand for veterinarians versed in issues of bioterrorism, emerging diseases, novel molecular biological approaches to diagnostics, and collaborative team research. Short research projects with laboratories dealing with EIDs would be useful and cost-effective in training the next generation of collaborative research veterinarians. Funding Sources Research on emerging diseases is funded largely by NIH programs, including a National Institute of Allergy and Infectious Diseases (NIAID) special emphasis program on biodefense and emerging diseases focused on agents listed as potential or actual bioterrorism agents by CDC and NIAID. NIH programs are heavily targeted to vaccine and drug development to counter traditional biological-warfare agents, with a relatively small focus on epidemiology of zoonotic EIDs. Research on EIDs of livestock, poultry, and aquaculture, including zoonoses and biothreat agents, is funded through CSREES and ARS and has focused on diagnostics, pathogenesis, and vaccines. Other EID research is funded through CDC (including epidemiology and vector-biology research), NSF (biocomplexity program, the NSF-NIH program on ecology of infectious diseases), other federal agencies, state agencies, and private foundations.

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Critical Needs for Research in Veterinary Science Ecosystem Health Examples of Critical Research Needs Definition of what constitutes a healthy ecosystem. Development of reliable and predictive indicators of ecosystem health. Characterization of the complex interaction between humans, domestic and wild animals, and the environment to predict risks to the health of these populations. Studies of the interaction between human and animal communities by multidisciplinary teams that include zoo veterinarians, ecologists and toxicologists, and public-policy experts to understand how human activities affect ecosystems and all their inhabitants, including humans. Research Agenda Immediate Priorities To maintain the health of an ecosystem, we must first define a healthy ecosystem and the thresholds that indicate health. Development of reliable and predictive indicators of ecosystem health should have high priority. It is a complex and time-consuming undertaking, and there appears to be no core set of indicators that can be applied to all ecosystems (Hodge and Longo, 2002; Eyles and Furgal, 2002). Ecosystem health could benefit from research to develop sentinel-species monitoring. Sentinel species are particularly sensitive to some agents (for example, pathogens and toxins) and act as indicators of their presence. Good examples are crows for West Nile virus and freshwater fish for some tumor-inducing chemicals. Mid-term Priorities Domestic and wild animals may be used as bioindicators or sentinels of ecosystem health (Tabor and Aguirre, 2004), and other reliable predictive indicators of ecosystem health could be developed, such as seabird dieoffs, which are often due to algal blooms, and amphibian deformities, which appear to be caused by increased prevalence of limb-bud parasites due to eutrophication of water-bodies or chemical pollution. Studies should be conducted on the effects of management practices on ecosystems and thus the health of domestic and wild animal populations and on which features of the interaction of humans and domestic and wild animals with

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Critical Needs for Research in Veterinary Science the ecosystem give rise to EIDs or risks to food safety. Ecologists and veterinary researchers should work together to determine the adequacy of information that is needed to support decision-making, especially if the decisions involve complex ecosystems that are not well understood. Long-term Priorities Systems theory and complexity-modeling approaches can be used to capture the important interactions that characterize open systems and to determine how social, economic and ecological variables should be weighed. Continuous research is needed to validate our concept of a healthy ecosystem. Strategies to Achieve Research Agenda The complex and wide-ranging interactions that characterize ecosystems require veterinary researchers trained in epidemiology, ecology, conservation, infectious disease, and other biological and social-science disciplines. A key strategy to move ecosystem-health research forward is to foster interdisciplinary research. Facilitating interdisciplinary research through interinvestigator, team, or institutional collaboration and a flexible posture on the part of agencies that fund the research are important. Funding Sources Funding for ecosystem-health research tends to be sporadic and is usually based on ecological studies on the effects of environmental changes on ecosystems. The research is not supported by one major agency but tends to be supported by small grants from a wide variety of state and federal government agencies (NOAA’s Sea Grant Program, NSF, the National Institute of Environmental Health Sciences), nongovernment and private agencies (various foundations committed to understanding environmental issues). Under NIH, NIEHS funds programs on the effects of toxic chemicals on ecosystem health. The establishment of large-scale and long-term interdisciplinary and collaborative research on ecosystem health is limited by changing and differing research priorities among funding agencies.

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Critical Needs for Research in Veterinary Science Social Policies, Societal Needs, and Expectations Including Animal Welfare Examples of Critical Research Needs Studies that objectively define, measure, and validate the benefits of social housing and environment enrichment. Science-based methods to measure stress and distress and stress-related effects in animals. Scientific analysis that uses quantifiable indicators to measure the effects of pharmaceutical agents and genetic modifications on animal welfare. Multidisciplinary studies of detection, control and prevention of large-scale zoonotic disease outbreaks that require disposal of large numbers of animals. Research Agenda Immediate Priorities An immediate need for veterinary research pertaining to social policies is to quantify measurable stress and distress characteristics in animals of all types to be used in objective evaluation of management practices for animal welfare. The physiological and welfare-related effects of pharmaceuticals used to alter metabolism or performance in animals should be evaluated. Effective methods for disposing of large numbers of animals subjected to diseases of natural or human introduction or to natural weather-related disasters need to be developed. The methods should be safe and socially acceptable. Mid- and Long-term Priorities New knowledge of the genome of each species should be applied in ways that enhance disease resistance, and minimize stress and distress responses to existing environmental conditions. Strategies to Achieve Research Agenda The critical kinds of research noted here receive only minor attention. The critical strategies to be used include priority-setting among the needs by funding agencies, provision for sustained support to enable the building of human and physical resources to conduct the needed research, and recognition that implementation of its results will have social and economic benefits.

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Critical Needs for Research in Veterinary Science Funding Sources A small amount of research to assess welfare requirements of agricultural animals is supported by USDA. Welfare studies on other animals rely on spotty financial support from private industry and foundations. Exotic and Caged Pets Examples of Critical Research Needs Characterization of the zoonotic pathogens capable of being carried by exotic species and also those pathogens that may be transmitted to domestic and wild animal populations. Improved methods of diagnosis and treatment of exotic animal diseases, especially in regards to safe and effective anesthetic and analgesic protocols. Determination of appropriate husbandry requirements for many exotic species. Research Agenda Immediate Priorities The discipline of exotic and caged-pet medicine should give high priority to the detection and characterization of new and emerging zoonotic infectious agents. Diagnostic tests are needed to identify zoonotic agents rapidly, and effective treatment and control measures for those zoonotic agents should be identified. Mid-term Priorities The growth of exotic-pet ownership has put considerable pressure on practicing veterinarians as they attempt to diagnose and treat little-known diseases with pharmaceutical agents that have never been investigated in the species of concern. Research is needed especially on appropriate and effective anesthetic and analgesic protocols in many species. Long-term Priorities A key long-term research issue is the appropriate husbandry requirements (nutrition, behavioral, and environmental) of the most commonly kept species

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Critical Needs for Research in Veterinary Science and species that are new and emerging. Because of the demanding and, in some cases, little understood husbandry requirements of many exotic species, there is concern about the welfare of many species kept in captivity (Keeble, 2003). Some commentators and animal-welfare advocacy groups take the position that exotic animals should not be kept as pets (Engebrestson et al., 2003). They believe that the complex behavioral and nutritional requirements cannot be met in captivity and that suffering and shortened life spans result. Research on the animal-welfare issues related to exotic-pet ownership and appropriate husbandry practices is required to determine which species should not be kept as pets. Strategies to Achieve Research Agenda The assessment of risks posed by and effects of zoonotic agents requires the application of genomics, proteomics, and sequencing of the agents. Research expertise in exotic- and caged-pet physiology, pathology, and immunology; advanced molecular biological techniques; epidemiology and population health; and diagnostic tests and therapeutic agents is needed. Experts would have to work with genome-sequencing centers and would require access to the appropriate biosafety laboratories. Funding Sources Funding for research on exotic-pet health and husbandry issues is sparse. Funds are available from some private funding organizations (for example, the Morris Animal Foundation) and from internal veterinary-college research funds (for example, pet- or companion-animal trust funds).