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A commentary on domestic animals as dual-purpose models that benefit agricultural and biomedical research¹

J. J. Ireland^*,2, R. M. Roberts, G. H. Palmer, D. E. Bauman and F. W. Bazer^#

^* Department of Animal Science, Michigan State University, East Lansing 48824-1225; and Department of Animal Science, University of Missouri, Columbia 65211-7310; and Department of Veterinary Microbiology and Pathology, and School for Global Animal Health, Washington State University, Pullman 99164-7040; and Department of Animal Science, Cornell University, Ithaca, NY 14853-4801; and ^# Department of Animal Science, Texas A&M University, College Station 77843-2471

	Abstract

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Research on domestic animals (cattle, swine, sheep, goats, poultry, horses, and aquatic species) at land grant institutions is integral to improving the global competitiveness of US animal agriculture and to resolving complex animal and human diseases. However, dwindling federal and state budgets, years of stagnant funding from USDA for the Competitive State Research, Education, and Extension Service National Research Initiative (CSREES-NRI) Competitive Grants Program, significant reductions in farm animal species and in numbers at land grant institutions, and declining enrollment for graduate studies in animal science are diminishing the resources necessary to conduct research on domestic species. Consequently, recruitment of scientists who use such models to conduct research relevant to animal agriculture and biomedicine at land grant institutions is in jeopardy. Concerned stakeholders have addressed this critical problem by conducting workshops, holding a series of meetings with USDA and National Institutes of Health (NIH) officials, and developing a white paper to propose solutions to obstacles impeding the use of domestic species as dual-purpose animal models for high-priority problems common to agriculture and biomedicine. In addition to shortfalls in research support and human resources, overwhelming use of mouse models in biomedicine, lack of advocacy from university administrators, long-standing cultural barriers between agriculture and human medicine, inadequate grantsmanship by animal scientists, and a scarcity of key reagents and resources are major roadblocks to progress. Solutions will require a large financial enhancement of USDA’s Competitive Grants Program, educational programs geared toward explaining how research using agricultural animals benefits both animal agriculture and human health, and the development of a new mind-set in land grant institutions that fosters greater cooperation among basic and applied researchers. Recruitment of outstanding scientists dedicated to using domestic animal models for agricultural and biomedical research, strong incentives for scientists to take advantage of training opportunities to write NIH grants, and greater NIH and USDA cooperation to sponsor the use of agricultural animals as dual-purpose animal models that benefit agriculture and biomedicine will also be necessary. In conclusion, the broad diversity of animal models needed for agricultural and biomedical research is at risk unless research priorities at the land grant universities are critically evaluated and financial support for such research is dramatically increased.

Key Words: domestic species • biomedical model • comparative animal model • dual-purpose animal model • farm animal research

	BACKGROUND

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Abundant, safe, high-quality, nutritious, and affordable meat, dairy products, and eggs, which are important components of nearly every human diet, are vital to US consumers, to the agricultural industry, and thus to the mission of USDA. Consequently, a strong, innovative research and development program dedicated to US animal agriculture is necessary to ensure food safety and to improve the quality and affordability of meat and milk, especially in an increasingly competitive global marketplace and during this period of escalating costs to produce animal products. However, despite the enormous economic value of animal agriculture to the US (approximately $110 billion), and the presence of many well-trained animal scientists at the 110 land grant institutions and 28 colleges of veterinary medicine in the United States, only approximately 0.038% ($35.4 million) of USDA’s $93 billion fiscal year 2007 budget was allocated to the National Research Initiative for extramural competitive grants for basic and applied research that directly involves agriculturally important domestic animals (cattle, swine, sheep, goats, poultry, horses, and aquatic species). On the other hand, the US Department of Health and Human Services, which is the principal federal agency that protects human health and provides health services, allocated 4.4% ($28.4 billion) of its $641 billion budget in fiscal year 2007 to National Institutes of Health (NIH) for extramural competitive grants programs. Despite the likelihood that numerous high-priority human health research areas (e.g., cancer, obesity, aging, cardiovascular disorders, infectious diseases, diabetes, fetal development, and infertility) could benefit from the appropriate use of agricultural species as biomedical models, the use of such animals in biomedical studies remains extremely low. Taken together, these limitations jeopardize not only the future global competitiveness of US animal agriculture, but also the potential for novel use of agricultural species as comparative biomedical animal models to resolve high-priority human health issues.

Few would challenge the concept that an "agricultural perspective" is appropriate and must be maintained at our land grant institutions. Nonetheless, the future of research in animal agriculture depends on strong graduate training programs, faculty engaged in cutting-edge research, and an infrastructure available within animal and veterinary science departments to preserve resources in terms of flocks and herds and a diversity of animal breeds. However, analysis of data in the USDA Current Research Information System illustrates a 44% loss of purchasing power and 22% loss of scientists supported by Cooperative State Research, Education, and Extension Service (CSREES) and state appropriations from 1985 to 2006 (Figure 1)! Analysis of data in the National Science Foundation’s Survey of Earned Doctorates showed that the number of doctoral degrees awarded from 1985 to 2004 in the animal sciences (including animal breeding and genetics, and nutrition) has declined by 30% (USDA Research, Education, and Economics Information System, 2007; Figure 2)! More recent data show that enrollment in MS and PhD programs in the animal sciences declined by 9 and 16%, respectively, between 2004 and 2006 (Food and Agricultural Education Information System, 2007). Faculty positions in animal sciences at some of the larger land grant institutions (e.g., the University of Missouri-Columbia) have fallen by more than 50% in the last 30 yr, with no apparent end to the decline in sight. Equally troubling is the rapid disappearance of breeds and genetic lines of domestic species, especially poultry (Fulton and Delany, 2003), which are critical to unraveling the importance of genetic variation to optimal health and well-being in animals and humans. For example, in a recent survey of land grant institutions (conducted in 2008 by Karen Plaut and James Ireland, Department of Animal Science, Michigan State University), 30 of 31 animal, dairy, and poultry science departments representing 29 states report significant downsizing or complete loss of beef, dairy, swine, or sheep herds or poultry flocks since 1985! Unless state and federal support for infrastructure at the land grant institutions is increased and the entire USDA-CSREES allocation for competitive grants in animal research is greatly revised upward, both of which require political support from key legislators, the entire research enterprise supporting animal agriculture will fragment, and at best become focused at just a few locations (Bazer, 2007; National Association of State Universities and Land-Grant Colleges, 2007). One alternative that might help this dire situation is the creation of a new funding agency dedicated to supporting agriculture through competitive grants (Danforth, 2006), but even this innovation may not be sufficient.

View larger version (25K): [in this window] [in a new window]   Figure 1. Loss of purchasing power and the decline in scientist years supported by Cooperative State Research, Education, and Extension Service (CSREES) and state appropriations for research using domestic species. Research includes animal production and animal protection programs in CSREES. Cooperative State Research, Education, and Extension Service dollars include expenditures from formula-funded projects and obligations from CSREES-administered grants. In the upper panel, the black bars reflect the combined funding provided by CSREES and state appropriations for research using domestic animals, whereas the hatched bars reflect the purchasing power of the CSREES and state appropriations after adjustment for the cumulative biomedical research and development price index since 1985. Numbers in parentheses indicate the cumulative inflation rate since 1985. Cumulative inflation rates were based on data obtained online (http://officeofbudget.od.nih.gov/UI/GDP_FromGenBudget.htm; last accessed August 18, 2008) from the National Institutes of Health Office of Budget. In the lower panel, the open bars reflect scientist years supported by the CSREES and state appropriations for research using domestic species. Data are from the Current Research Information System (http://cris.csrees.usda.gov; last accessed August 18, 2008) and were provided by F. A. Moore and D. L. Hamernik on February 15, 2008.

View larger version (16K): [in this window] [in a new window]   Figure 2. Changes in the number of PhDs awarded in animal science-related fields of study, including animal science, breeding and genetics, and nutrition. Data were obtained from the National Science Foundation "Survey of Earned Doctorates" from all US academic institutions (USDA Research, Education, and Economics Information System, 2007).

	OBSTACLES AND POTENTIAL SOLUTIONS

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The key obstacles that impede the use of farm animals as dual-purpose models for animal agriculture and biomedicine, and potential solutions to these problems are discussed within the following 4 interrelated areas.

The Advocacy Obstacle

Lack of advocacy is the prime impediment to the enhanced use of agricultural animals for biomedical research. Simply put, scientists unfamiliar with agricultural species as animal models, university administrators, officials at USDA and NIH, politicians, and the public at large do not appreciate the advantages of agricultural animals as comparative animal models for biomedical research. The advantages of domestic animal models are particularly compelling in terms of translational research, moving concepts from the laboratory to human health applications. These same individuals are also generally unaware of the past impact such research has had on societal well-being and human health (http://www.adsbm.msu.edu), nor are they conscious of the high quality of basic science being performed in animal and veterinary science programs. This knowledge void creates major institutional and funding barriers throughout academia. Moreover, it prevents quality research from being conducted pro-actively to address key issues in agriculture through the use of state-of-the-art genomics biology to benefit production animal agriculture as well as human and animal health and well-being.

Potential Solution

Vigorous, broad, and proactive advocacy and educational programs, administered jointly by land grant institutions [e.g., Academic Programs Committee on Organization and Policy (ACOP) and National Association of State Universities and Land Grant Colleges (NASULGC), www.nasulgc.org, last accessed August 18, 2008; Experiment Station Committee on Organization and Policy (ESCOP), http://escop.ncsu.edu, last accessed August 18, 2008), the Association of American Veterinary Medical Colleges (AAVMC), http://www.aavmc.org, last accessed August 18, 2008] and appropriate animal industries will be required to enhance the use of domestic species for research. These programs must be strong advocates to explain the past contributions and future opportunities of research on agricultural animals and their value as comparative animal models for research that benefits animal agriculture and human health. The advocacy and educational program can take many forms, including symposia at universities, funding agencies, and scientific and public meetings such as recent workshops (http://www.adsbm.msu.edu). They can also involve the development of informative Web sites (e.g., http://www.adsbm.msu.edu) that provide historical and current examples of the importance and advantages of domestic species as biomedical models in a variety of critical areas of research. For example, it is probably not well known that 17 Nobel Prizes have been awarded to scientists who conducted research with cows, chickens, horses, or sheep as biomedical models during their studies.

Land Grant Barriers

The long-standing cultural idiosyncrasy that biomedical research is "inappropriate" to the land grant mission is an unfortunate attitude permeating the culture of traditional agriculture and belief system of many of its administrators and influential faculty members. This cultural barrier explains in part why agricultural colleges have historically been segregated from colleges of human medicine and veterinary medicine, and the basic life sciences disciplines. This science-segregation policy at land grant institutions diminishes communication, the sharing of resources, and collaboration among scientists who could benefit from these interactions. At many institutions, the isolation of animal science programs, in particular, has contributed to a lack of recruitment of top-notch researchers into the area and a failure to tap into the funding available through using agriculturally important animal species for biomedical research. There is often little incentive for animal scientists to collaborate with biomedical scientists, engineers, and others who could bring an interdisciplinary perspective and novel insights into traditional animal science thinking. The land grant schools, hidebound by traditional concepts of the type of research that should be supported, have also failed to provide mechanisms to encourage scientists to think "outside the box."

Potential Solutions

Enhanced use of agricultural animal species for biomedical research requires the development of a new mind-set within land grant institutions, a mind-set that fosters greater cooperation among basic and applied researchers across a variety of departments, disciplines, and industries. Administrators are aware that the protected island fortress of agriculture is becoming an anachronism that is no longer viable as state and federal support declines. Indeed, traditional agricultural research cannot thrive in isolation. Consequently, administrators must not back away from defending the use of farm animals for biomedical research in animal science departments, especially when dealing with their traditional stakeholders. It is highly recommended that leaders of land grant institutions seek guidance from 2 or 3 successful institutions with existing strong cooperation between colleges of agriculture and the rest of the campus (e.g., University of Illinois, University of Missouri). Suggested ways to strengthen cooperation among animal science departments, medical schools, and basic science departments (Table 1) include the following:

• Create a list of the high-priority research areas at NIH that currently use or could benefit from the use of agricultural animals as biomedical models, and use these high-priority research areas as a blueprint for future faculty hires and incentive plans to foster interdisciplinary or multidisciplinary research.
  
• When the opportunity exists, hire new administrators with the leadership skills and vision to
  1. Resolve philosophical differences among animal science departments, basic science departments, colleges of veterinary medicine, schools of public health, and colleges of medicine, and
     
  2. Enhance cross-departmental research programs.
     
  
  
• Hire faculty and department chairs in animal science and the basic sciences within colleges of veterinary medicine who are not trained simply in traditional animal and veterinary sciences, but who also have experience in, or at least the appreciation of, newer and emerging technologies and the broad scope of animal sciences for society as a whole. Such leaders should be prepared not only to serve traditional agricultural stakeholders, but also to interact with the broader life science community.
  
• Hire new faculty with joint appointments in medical schools and basic science departments, or interfacing with existing animal scientists in cutting-edge research programs in medical schools, veterinary schools, and basic science departments.
  
• Create incentives for collaboration among animal, basic, and clinical research scientists by
  1. Providing leverage and seed funds for interdisciplinary research.
     
  2. Facilitating and promoting the sharing of facilities and resources.
     
  3. Encouraging animal science faculty members to collaborate with nonagriculture colleagues to submit NIH grants and to increase publications in high-impact biomedical and basic science journals.
     
  4. Creating centers of excellence committed to the use of agricultural animal species as comparative animal models. One long-term approach to generate the funds necessary to stimulate interdisciplinary research is to reduce the duplication of research, extension, and teaching efforts in agriculture at land grant institutions. The cost savings from formation of "regional clusters" of land grant universities to conduct extension, education, and research, coupled with USDA formula funds, could be used to sponsor creative research by new or existing productive faculty members interested in generating preliminary data important for both agriculture and biomedicine.
     
  
  

Limited Diversity of Species Supported as Biomedical Models by the NIH

Research involving domestic animals has a well-established role in improving animal agriculture, but a poorly understood, yet critical, role in advancing biomedical research to enhance human health. For example, the relatively recent completion of the sequencing of the human genome provided the genetic blueprint that will eventually help elucidate the interrelationship of genetic variation and the environment with human health. As this crucial new genetic information is generated, it will provide the fundamental new knowledge that scientists need to design more effective preventive or therapeutic methods to eliminate or combat many of the factors that currently have a negative impact on human health (e.g., cancer, cardiovascular disease, obesity, alcoholism, low birth weight, and infertility). However, despite elucidation of the sequence of the human genome, the scientific challenge of translating this information to advance human medicine is daunting, especially because studies involving humans are both expensive and limited to specific interventions. Therefore, a diversity of comparative animal models from different evolutionary ancestries are required not only to identify highly conserved genes and to understand gene function, but also to extrapolate genetic information from comparative animal models to humans (Gibbs et al., 2004). The selection of the most appropriate animal model includes considerations such as size and experimental tractability (e.g., ease of surgical manipulation, frequency of blood sampling, availability of large volumes of blood or tissues for assay, efficiency of cloning, and xenotransplantation), as well as the species physiology and disease pathogenesis that best recapitulate human biology and disease.

Despite the value of using diverse species to understand the evolutionary history of mammalian genomes (Gibbs et al., 2004) and the clear advantages of domestic animals in certain biomedical research applications (http://www.adsbm.msu.edu), rodents (especially mice) remain by far the predominant experimental animal model used for biomedical research. For example, an analysis of all funded NIH grants from 2002 to 2006 for studies that used rodent or domestic species models revealed that approximately 98% used rodent models (Table 2). Moreover, during those years the number of funded grants for studies that used domestic species declined by 30% (Table 2). A recent search of the Computer Retrieval of Information on Scientific Projects (http://crisp.cit.nih.gov/; last accessed August 18, 2008) database of all abstracts of research programs and projects funded in 2008 by the Department of Health and Human Services revealed that 4,134 projects used mouse or rat models, but only 115 projects used domestic species as biomedical models. Another Computer Retrieval of Information on Scientific Projects search for projects funded in 2008 showed that 23,173 projects used mice or rats as a source of reagents, pathogens, or cell lines, or as experimental models, whereas 1,762 projects made use of domestic species. Three conclusions can be drawn from these data. First, these analyses provide clear evidence of increasing reliance on a single-species animal model for biomedical studies. Second, only a small fraction of biomedical research projects take advantage of domestic animals. Third, the use of domestic animals as comparative animal models is in decline.

It is unclear why so few grant proposals that use domestic species are funded through NIH. One likely explanation is that there are relatively few animal scientists with the necessary training, expertise, or motivation to develop and submit high-quality applications with the potential of being funded by NIH. This is coupled with the fact that few scientists on NIH review panels recognize and understand the unique opportunities offered from research with domestic animals. The long-standing land grant tradition of providing "hard money" support for research has resulted in having scientists in agricultural experiment stations that do not depend on grants to conduct research; thus, they have limited or no experience in writing grant applications. In short, grantsmanship among animal and veterinary scientists is generally weak, and few scientists within colleges of agriculture have been compelled to write grant proposals to keep their research programs alive and even to provide their own salary support.

Potential Solutions

To maximize the potential of using domestic animal species as models for NIH-supported biomedical research, universities must strongly encourage and provide incentives for animal and veterinary scientists to attend intensive training workshops to learn how to write competitive NIH grants and justify animal models (Table 3). Furthermore, scientists must strive to publish in the highest quality journals and to place their scientific findings in a broad context of biology and biomedicine. To do so, the flagship land grant universities must dedicate efforts toward recruiting outstanding scientists who conduct research with domestic animals as biomedical models and toward distinguishing themselves from other animal science programs at 4-year colleges and universities that do not offer doctoral degrees.

Limitations in Research Tools

For some agricultural animal species, the resources to conduct creative research are limited. Challenges faced by animal scientists include 1) a lack of available species-specific tools and reagents, including antisera and antibodies, cytokines, and growth factors; 2) small or poorly managed collections of cell lines, germplasm, and databases for computational biology and bioinformatics; 3) inadequate genetic resources, such as defined inbred lines with characterized genetics; and 4) a lack of required genetic tools, such as genomic sequences for sheep, turkeys, and aquatic species; inexpensive microarrays for a range of agricultural animal species; and clone sets and primer sets for major genes.

Potential Solutions

The USDA, NIH, and National Science Foundation and industry must cooperate to develop strategic plans, set priorities for research, and generate the financial support necessary to fund the development of critical resources.

Summary and Conclusions

Agriculturally important animals can be used not only for research to improve animal agriculture, but also as biomedical models that often more closely mimic human physiology and disease than do rodent models. Because research using domestic animals requires special facilities and expertise, highly qualified research scientists using domestic animals for research in animal agriculture, as biomedical models, or both need support by federal funding agencies to enhance their unique contributions to new agricultural and medical knowledge. Consequently, USDA and NIH should jointly advance domestic animals as dual-purpose models to resolve high-priority problems common to both animal agriculture and biomedicine. First, the missions of USDA and NIH are inextricably linked because the health, well-being, and fertility of domestic species underpin the availability and affordability of high-quality, nutritious food, which contributes directly to health maintenance and the prevention of chronic diseases in humans. Second, genetic lines of agricultural animals, facilities, and faculty expertise are valuable resources that are substantially underused for studies to benefit human health. Therefore, enhanced use of domestic animals as biomedical models will provide the additional benefit of generating important new information directly relevant to many areas of research in animal agriculture.

In conclusion, the immediate challenge is for stakeholders to continue to embrace high-quality research and to communicate, cooperate, and work unselfishly to eliminate the obstacles impeding the use of domestic animals as animal models in agriculture and biomedicine to ensure that citizens of the world will continue to be provided with a safe and abundant supply of food, excellent health care, and a high quality of life.

	Footnotes

 
¹ This research was supported by National Research Initiative Competitive Grants 2004-38859-02183 and 2007-35206-17904 from the USDA Cooperative State Research, Education and Extension Service (Washington, DC), 1 U13 HD049212-01 from the National Institute of Child Health and Human Development (Rockville, MD) and National Institute of General Medical Sciences (Bethesda, MD), and by funds from both the Texas and Michigan State University Agricultural Experiment Stations to JJI.

² Corresponding author: ireland{at}msu.edu

Received for publication April 8, 2008. Accepted for publication June 9, 2008.

	LITERATURE CITED

Top Abstract BACKGROUND OBSTACLES AND POTENTIAL... LITERATURE CITED

 


Bazer, F. W. 2007. How to boost agricultural research. The Scientist 21:29.

Danforth, W. H. 2006. Funding basic agricultural research. Science 314:223.[Abstract/Free Full Text]

Food and Agricultural Education Information System. 2007. Animal Science Graduate Enrollment. http://faeis.ahnrit.vt.edu/newsletter/december_07/newsletter.html Accessed March 14, 2008.

Fulton, J. E., and M. E. Delany. 2003. Genetics: Poultry genetic resources—Operation rescue needed. Science 300:1667–1668.[Abstract/Free Full Text]

Gibbs, R., G. Weinstock, S. Kappes, L. Schook, L. Skow, and J. Womack. 2004. Bovine Genomic Sequencing Initiative: Cattleizing the Human Genome. http://www.genome.gov/Pages/Research/Sequencing/SeqProposals/BovineSEQ.pdf Accessed August 18, 2008.

National Association of State Universities and Land-Grant Colleges. 2007. Creating Research, Extension, and Teaching Excellence for the 21st Century (Create-21). http://www.create-21.org/in-dex.htm. Accessed April 4, 2008.

Overton, J. 1994. Investing in the National Research Initiative: An Update of the Competitive Grants Program of the U.S. Department of Agriculture. Natl. Acad. Press, Washington, DC.

USDA Research, Education, and Economics Information System. 2007. Reports: NSF/SED Reports. http://www.reeis.usda.gov/portal/page?_pageid=53,545315&_dad=portal&_schema=portal&smi_id=38 Accessed April 4, 2008.

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This Article Free Via Open Access Abstract Full Text (PDF) All Versions of this Article: jas.2008-1088v1 86/10/2797    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ireland, J. J. Articles by Bazer, F. W. Search for Related Content PubMed PubMed Citation Articles by Ireland, J. J. Articles by Bazer, F. W.