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Abstract: Despite the enormous economic
value of U.S. animal agriculture (>$110 billion), only 0.034% of
USDA’s $106 billion ($36.5 million in 2004) annual budget is
allocated to the National Research Initiative (NRI) for extramural
competitive research grants involving agricultural animals (cattle,
hogs, sheep, goats, poultry, horses, and aquatic species). The U.S. Department of Health
and Human Services allocates 4.1% of its $548 billion ($22.4 billion
in fiscal year 2004) to NIH for extramural
competitive grants programs. However, despite the likelihood that
high priority human health research areas could be enhanced by
use of agricultural species as biomedical models, rodents are the predominant biomedical animal
model. These limitations jeopardize the future competitiveness of U.S. animal
agriculture, and the use of agricultural animals as novel comparative
biomedical models to resolve high priority human health issues.
Because the USDA extramural competitive grants program is insufficient
to fully support research directly related to production, health and
well-being of farm animals, many talented animal scientists must
seek biomedical related sources of funding to maintain their research
programs. Consequently, unless the traditional research focus of
animal science departments is expanded to include biomedicine, bright
young scientists may not be attracted to animal agriculture, and
research involving agricultural animals is likely to become a minor
part of life sciences in colleges and universities throughout the U.S.
As a result of these concerns, USDA, NICHD/NIGMS, Texas A&M
University and Michigan State University organized a workshop that
identified the following as key obstacles impeding use of agricultural
animals as biomedical models: lack of broad advocacy, long-standing
cultural barriers at land grant institutions, poor grantsmanship by
animal scientists and “genus inequity” (rodents favored over
agricultural animals) at NIH, and scarcity of key reagents and
resources. Solution to these problems included: development of
a vigorous proactive education program to explain how research on
agricultural animals benefits both animal agriculture and human health;
development of a new “mindset” within land grant institutions that
fosters greater cooperation among basic and applied researchers in a
variety of departments; development of intensive training opportunities
and incentives for animal scientists to write NIH grants and justify
animal models; greater interagency (NIH, USDA) cooperation to advocate
use of agricultural animals as novel alternative comparative animal
models in high priority areas of biomedical and agricultural research;
revision of the NIH peer review system to remove inappropriate “genus
inequity” problems; improved networking among scientists that use
agricultural species as comparative animal models; and organization of
the research priorities, strategic plans, and financial support
necessary to develop the critical resources for research with
agricultural animal species.
The
immediate challenge is to form a task force willing to implement
the changes necessary to increase use of agricultural species as
comparative animal models for biomedical research.
Introduction: Abundant
safe, high quality, nutritious and affordable meat, milk and eggs,
which are important components of nearly every human being’s diet, are
vital to U.S. consumers, to agriculture, and thus to USDA’s mission.
Consequently, a strong innovative research and development
program dedicated to U.S. animal agriculture is clearly necessary to
ensure food safety and to improve the quality and affordability of meat
and milk, especially in an increasingly competitive global
marketplace. However, despite the
enormous economic value of animal agriculture to the U.S. (>$110
billion, [1]), and the presence of many well-trained animal scientists
at the 94 land grant institutions in the U.S. [2], only about 0.034% of
USDA’s $106 billion ($36.5 million in fiscal year 2004) annual
budget is allocated to the National Research Initiative (NRI) for
extramural competitive grants for basic and applied research that
directly involves agriculturally important animals (cattle,
hogs, sheep, goats, poultry, horses, and aquatic species). On the other hand, the U.S.
Department of Health and Human Services, which is the principal federal
agency that protects human health and provides health services,
allocates 4.1% of its $548 billion ($22.4 billion in fiscal
year 2004) to NIH for extramural
competitive grants programs. However, 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 be enhanced by the
appropriate use of agricultural species as biomedical models, at
present, rodents are the predominant
comparative animal model used for biomedical studies.
Taken together, these limitations jeopardize not only the future competitiveness of U.S. animal
agriculture, but also the potential use of agricultural species as
novel comparative biomedical animal models to resolve high priority
human health issues. Consequently, a task force of policy makers,
officials and administrators at land grant institutions and federal
funding agencies, scientists, and the public must be formed to work
cooperatively and vigorously towards a resolution of these complex
problems.
In large
part because the USDA extramural competitive grants program is
woefully insufficient to fully support research directly related to
production, health and well-being of farm animals, many talented animal
scientists must seek biomedical related sources of funding to maintain
their research programs. Consequently, unless the traditional
research focus of animal science departments is expanded to include
biomedicine, bright young scientists may not be attracted to animal
agriculture, and research involving agricultural animals is likely to
become a minor part of life sciences in colleges and universities
throughout the U.S. As a result of these concerns, USDA,
NICHD/NIGMS, Texas A&M University and Michigan State University
organized a workshop (October 29-31, 2004, Advantages of
Agriculturally Important Domestic Species as Biomedical Models [3]),
with the following objectives:
 To provide a
forum to exchange ideas among scientists that use agricultural
animals as biomedical models with officials from NIH and USDA,
and university administrators at land grant institutions.
To
emphasize the scientific importance of agricultural animals as
biomedical models and acknowledge the numerous ways they are
contributing to our current understanding of human and animal health
and well-being, and animal agriculture.
To
identify high priority research areas that could be enhanced by use of
agricultural animals as biomedical models (Table 1).
To
explore the potential need and justification for an interagency program
that would be co-funded by one or more institutes within the NIH and by
USDA-CSREES and perhaps others (industry, state governments) to support
high priority research that could be advanced by use of agricultural
animals as comparative biomedical models.
The workshop was attended by 114 invitees with broad experiences
relevant to reliable assessment of the general “status” of research
involving agricultural animals. These experiences included
principal investigators of USDA- and NIH-funded research programs that
use agricultural animals, members of the National Academy of Sciences,
directors of university centers of excellence, career scientists with
extensive service on USDA and NIH panels, editors of scientific
journals, university administrators, USDA and NIH administrators, USDA
science advisors, current and past presidents of national scientific
societies, and invited graduate students and postdoctoral trainees.
This group, though quite varied in its perspectives, was able to bring
a mixture of balance, insight, and on-the-job experience to what is an
issue of great concern.
During the
workshop, 13 lectures were presented by internationally
recognized scientists representing a diversity of research areas
(reproduction and development, nutrition, health and disease, and
genomics and advanced technologies). Also, a series of intensive
discussions were held to address a variety of questions relevant to
enhanced use of agricultural animals as biomedical models.
The
highlight of the workshop was identification of a number of key
obstacles impeding use of agricultural animals as biomedical models
within four major interrelated areas (advocacy, land grant
institutions, NIH and resources) and potential solutions to these
obstacles.
I. The Advocacy Obstacle:
A
lack of advocacy is the prime impediment to the 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. They are
also unaware of the past impact such research has had on societal well
being and human health and are generally scornful of the high quality
of basic science being done in animal science departments (The “Moo U”
factor!). This knowledge void creates prejudice and major
institutional and funding barriers throughout academia.
Solution:
A vigorous, broad, and proactive advocacy/education program,
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 [4];
and Experiment Station Committee on Organization and Policy, ESCOP
[5]), federal funding agencies and appropriate animal industries, will
be necessary to explain the potential impact and past contributions of
research on agricultural animals and their value as comparative animal
models for research that benefits animal agriculture and human health.
The advocacy/education program could take many forms, including
symposia at universities, funding agencies and scientific and public
meetings, and development of an informative web site.
II. 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 of many of its
administrators and influential faculty members. This cultural
barrier in part explains why agricultural colleges have historically
been segregated from colleges of human and veterinary medicine and the
basic life sciences disciplines. This science-segregation policy
at land grant institutions diminishes communication, sharing of
resources, and collaboration among scientists who could benefit from
much closer association with their colleagues. At many institutions,
the isolation of animal science programs, in particular, has
contributed to lack of recruitment of top notch researchers into the
area and a failure to tap into the funding available for biomedical
research on agriculturally important animal species. There is often
little incentive, and frequently disincentives 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 their traditional concepts of what sort of research should be
supported, have also failed to provide mechanisms to encourage
scientists to think “outside the box”.
Solutions:
Enhanced use of agricultural animal
species for biomedical research depends especially on development of a
new “mindset” within land grant institutions that fosters greater
cooperation among basic and applied researchers within and among a
variety of departments including medical and basic science faculty and
industry. Administrators are aware that the “protected island fortress”
of agriculture is becoming an anachronism and 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 needed changes in farm animal 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 two or three 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 between animal science departments, medical schools, and
basic science departments include the
following:
Creating
a list of the high priority research areas at NIH that
currently use or could benefit by use of agricultural animals as
biomedical models (Table 1) and using these high priority
research
areas as a “blueprint” for future faculty hires and incentive plans to
foster interdisciplinary/multidisciplinary research.
Hiring
of new administrators with leadership skills and vision to: i)
resolve philosophical differences between animal science departments,
basic science departments and medical schools, and ii) enhance
cross-departmental research programs.
Hiring
of faculty and chairs who are not simply trained in traditional animal
sciences, but who also have experience 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. Such leaders should be encouraged
to continue to be active in research rather than becoming full time
administrators.
Hiring
new faculty with joint appointments in medical schools and basic
science departments and/or interfacing existing animal scientists with
cutting-edge research programs in medical schools, veterinary schools
and basic science departments.
Creating incentives for collaborations between animal, basic and
clinical research scientists by:
i. Providing
leverage and seed funds for interdisciplinary research.
ii. Facilitating and
promoting sharing of facilities and resources.
iii. Encouraging
animal science faculty to collaborate with non-agriculture colleagues
to submit NIH grants and to increase publications in high-impact
biomedical and basic science journals.
iv. Creating centers of
excellence committed to 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 interested in generating preliminary data important
for both agriculture and biomedicine.
III. Grantsmanship and “Genus
Inequity”:
Grantsmanship
by animal and veterinary scientists is probably not
strong when compared with biomedical and basic scientists because
pressures to write NIH grants are less at many land grant institutions
compared with their biomedical and basic science counterparts.
Nevertheless, scientists with successful track records of NIH funding
and with experience on NIH review panels indicate that “genus inequity”
(rodents favored over agricultural animals as biomedical models)
clearly exists in NIH review panels for a variety of reasons:
Grant
applications that use agricultural species as comparative animal models
require extensive justification and additional preliminary data
compared with applications using rodent models.
Lack of
appropriate expertise on review panels (e.g., some panels are
composed primarily of members experienced with rodent or primate models
or only have experience with transgenic mice or cell lines.).
Limited
knowledge of resources available to scientists that use agricultural
animal species as models.
The quality of publications describing research in agricultural
animals, which is the foremost criteria used to assess the “track
record” of principal investigators, may be perceived as inferior
because the preponderance of livestock publications are in
commodity-related rather than biomedical journals.
Solutions: Better tactics are necessary to overcome
the obstacles impeding use of agricultural species as comparative
animal models:
Universities
must create intensive training opportunities for animal scientists to
write NIH grants and justify animal models (Table 2), and provide the
“motivation” for participation.
Proactive
forms of advocacy should be implemented to enhance awareness of
the broader scientific community, NIH officials and policy makers of
the potential uses and benefits of agricultural animals as biomedical
models. To accomplish this objective most effectively, greater
interagency (NIH, USDA) dialog and cooperation must be established not
only to advocate use of agricultural animal models in an effective
manner, perhaps by sponsoring symposia or workshops with awardees from
both agencies at biomedical meetings, but also to develop requests for
applications (RFAs), training grants, leverage grants and seed grants
for use of agricultural species as novel alternative comparative
animal models in high priority areas of biomedical and agricultural
research.
Working with
the NIH Center for Scientific Review, a key revision of the NIH
peer review is necessary to address real and perceived “genus inequity”
problems by explaining in application kits the major sources of concern
for agricultural animals as biomedical models that should be addressed
in applications, by ensuring that Scientific Review Administrators
(SRAs) and reviewers have appropriate expertise and appreciation for
agricultural animals as biomedical models, and by ensuring that the
SRAs prohibit “inappropriate” criticisms of agricultural species as
animal models during written and oral reviews of research applications.
NIH
could improve networking among scientists that use agricultural species
as comparative animal models by advertising to land grant universities
the successful NIH grants using agricultural animals as biomedical
models. Better networking would lead to better utilization of expensive
resources and provide additional opportunities for motivated animal
scientists to generate preliminary data.
IV. Research tools are
limited:
Resources
to conduct creative research for some agricultural animals
are limited compared with rodents. Challenges faced by animal
scientists include: 1) lack of available species-specific tools and
reagents, including antisera and antibodies; 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) lack of
required genetic tools, such as genomic sequences for pigs, sheep,
turkeys, horses and aquatic species, inexpensive microarrays for
a range of agricultural animal species, and clone sets and primer sets
for major genes.
Solutions:
To resolve these problems, universities, federal
funding agencies, and industry must work cooperatively to develop
strategic plans, set priorities for research, and generate the
financial support necessary to fund development of critical resources
for research with agricultural animal species.
V. Action Plan and the Future:
The
immediate key challenge is to form a task force willing to
communicate, cooperate and work unselfishly to develop and implement an
action plan to enhance use of agricultural animal species as biomedical
models. The action plan will have short- (Table 3), intermediate-
(Table 4),
and long-term (Table 5) goals to begin to resolve
obstacles
and implement solutions to increase use of agricultural species as
comparative animal models for biomedical research.
The
spirit of this initiative can be summarized in part through recognition
that agriculturally important animals have a rich history as models for
the study of human medicine. This is especially true in the
fields of biochemistry, enzymology, and endocrinology where many
proteins were first isolated and purified from various agricultural
animal species. Agriculturally important animals have been and
are experimental models of choice in reproductive physiology where the
basic techniques of artificial insemination, superovulation, oocyte
culture, in vitro fertilization and embryo transfer were
developed and where fundamental sciences are being extended to cloning
and stem cell research.
Cattle,
for example, have long been studied for complex traits
influenced by multiple genes as well as environmental factors.
These so called “quantitative traits” are now targeted by the human
health research community. Cardiovascular health, obesity, and
several cancers are examples of complex traits segregating in breeding
populations of cattle. The understanding of what makes cattle
breeds different with respect to reproduction, lactation, growth, bone
structure, fat deposition, altitude and heat tolerance, and resistance
to specific pathogens will be invaluable in elucidating related
physiological processes important to human health.
Genomic
variation is clearly a major factor in host resistance to
pathogens in humans and animals. Identification of specific genome
sequences that predispose susceptibility/resistance to disease will be
fundamental to advancing animal health within the livestock industry,
to averting accidental or terrorist-initiated epidemics, and to
developing models of human gene/pathogen interaction. Genomic
variation also underlies traits such as growth, body composition,
lactation, and reproductive health. The working draft of genome
sequences of agriculturally important animals will, therefore, provide
an invaluable resource for discovery of genes and their functions to
benefit human health, animal health and production animal
agriculture. The present long-term challenge is to chart a course
for funding for both rodent and agriculturally important animal models
that will ensure that we continue to provide citizens of the world with
the basic need for a safe and abundant supply of food, excellent
healthcare, and a high quality of life.
Table 1. Research areas (not
prioritized) that potentially could be advanced by use of
agricultural animals as biomedical models.
_______________________________________________________________________
Epigenetics and environment: effect of
photoperiod, global warming, seasonality, and elevation on modification
of gene function
Reproduction: gametogenesis, gonadal
function, infertility
Aging: skeletal diseases, especially
chicken and pig models; bone metabolism and
osteoarthritis,
especially the horse model; reproduction, especially beef cattle and
mares
Obesity: genetic, dietary, hormonal
influences on pre- and post-natal adipose tissue development using pig
model
Pregnancy: placental growth, angiogenesis,
congenital and birth defects, developmental biology especially
chickens, fetal programming especially sheep to study stress,
malnutrition, effects of exposure of fetuses to androgens
and environmental toxins on adults, molecular/cellular basis of
parturition and premature birth
Diabetes Types I and II
Therapeutics: xenotransplantation, gene
therapy, stem cells, “Farmaceuticals”;
Toxicology, environmental endocrine
disrupters
Neurobiology: behavior, stress, learning,
pheromonal communication, neuroendocrinology
Immunology: autoimmune disease,
inflammation, innate and mucosal
Cardiovascular disorders such as
diet-induced artherosclerosis and lethal cardia tachyarrhythmias
(ventricular fibrillation) using minature or normal
pigs
Nutrition: energetic balance including
homeostatic mechanism, regulation of metabolism, use of neonatal piglet
as pediatric model for studies of nutrition, metabolism and
gastroenterology
Ophthalmology: retinal degeneration,
retinitis pigmentosa, macular degeneration
Comparative physiology (e.g.,
Understanding of what makes cattle breeds different with respect to
reproduction, lactation, growth, bone structure, fat deposition,
altitude and heat tolerance, and resistance to specific pathogens will
be invaluable in elucidating related physiological processes important
to human health.)
Radiation biology
Biomechanics
Renal biology
Diseases: Transmissible Spongiform
Encephalopathies (TSE); Respiratory Syncytial Virus (RSV); Crohn’s
Disease; sexually transmitted diseases (STD); enteric including
Transmissible Gastroenteritis (TGE); viral, E. coli
01578; cancer including prostate, breast, ovary (chicken),
hematopoiesis, leukemia; cattle as a model for salmonellosis,
tuberculosis and cryptosporidiosis; pathogen transmission of emerging
diseases that infect animals and humans such as use of cattle to study
tick-borne infections
Disorders: liver, epilepsy, and sleep
such as narcolepsy
Table 2. Attributes of
successful NIH grants.
________________________________________________________________________
§
Simple questions with appropriate background were posed
§
Substantial and compelling preliminary data were included
§
Current gaps in knowledge were addressed
§
Unique comparative value of the chosen model was explained (cannot
recapitulate observations in rodents)
§
How the model led an area of research and was used to answer the
questions posed were explained carefully
§
A broad range of disciplines and expertise was employed to resolve
problems
§
Potential bias of reviewers was addressed
§
Senior investigators had a significant track record of success
including publications in high quality journals
§ Applications
were critiqued by experienced investigators prior to submission
and the advice of the panel manager, SRAs, and reviewers was heeded
Table 3. Short-term goals.
________________________________________________________________________
Engage “top”
university administrators at land grant institutions to provide
incentives for faculty to compete for extramural grants at agencies
other than USDA and to assist motivated scientists in preparation of
such applications for review.
Advertise
attributes of successful grant applications to NIH to motivated faculty
(see Table
2).
Meet and seek
advice from Director of Center for Scientific Review on NIH obstacles.
Identify advocates
at NIH, USDA and other agencies to assist scientists in the
implementation of strategies to enhance use of agricultural animals in
biomedical research.
Hold workshops at
NIH to inform SRAs and appropriate administrators of advantages of
agricultural animals as biomedical models.
Form committees to
engage organizers of scientific meetings to promote/showcase
agricultural animals, primate and rodent
models addressing high priority human health problems (e.g., To
promote agricultural species as important comparative animal models, a
central fund from all land grant institutions could be created and used
to partially sponsor the aforementioned special animal models’ symposia
at national meetings.).
________________________________________________________________________
Table 4. Intermediate-term goals.
________________________________________________________________________
Set up
“brainstorming” sessions between USDA and NIH to improve interagency
cooperation.
Improve awareness
of scientists using rodents as models of the importance of agricultural
animal species as models for biomedical research by publicizing models
to other research groups (e.g., hold joint meetings with
scientists using agricultural animal and rodent models).
Organize follow-up
meetings involving scientific administrative staff at the NIH National
Center for Research Resources and various other institutions at NIH,
other federal funding agencies, and USDA.
Seek joint
NIH-USDA support for symposia to identify novel uses of agricultural
animals in biomedical research
Establish NIH-USDA
databases for central sharing of resources.
Institutions must
strongly encourage faculty to apply for more NIH grants.
Scientists need to
publicize/promote better animal models to colleagues in agriculture and
biomedicine.
Develop advocates
in agriculture and biomedical communities: include and inform commodity
groups, animal industry, and pharmaceutical and biotechnology
industries.
Joint NIH-USDA
training grant program to integrate biomedical and animal sciences.
Organize meeting
with USDA, NCRR and NHGRI to develop the strategic plans and research
priorities necessary to develop key reagents and “tools” to advance
research with agricultural animals as biomedical models.
________________________________________________________________________
Table 5. Long-term goals.
________________________________________________________________________
Organize
inter-agency program for new alternative models to rodents for high
priority areas of biomedical research.
Ensure the
“agricultural perspective” is maintained at land grant institutions.
Either USDA officials must be engaged/convinced to increase
dramatically the USDA budget allocation for competitive grants in
animal research and/or political support must be garnered to create a
new funding agency (e.g., National Institute of Agriculture and
Food Science [6]).
Develop
alternative high margin markets for animal products to re-invigorate
industry support for animal research.
Develop
interagency support for training, sabbaticals and career development
for scientists to use agriculturally important animal species as models
for high priority problems in agriculture and biomedicine.
________________________________________________________________________
References:
1.
http://www.usda.gov/nass/pubs/agr04/acro04.htm.
2.
http://www.higher-ed.org/resources/land_grant_colleges.htm
3.
http://www.adsbm.msu.edu/
4.
www.nasulgc.org
5.
http://www.cals.ncsu.edu:8050/escop/
6. http://www.biomedcentral.com/news/20041116/02/printerfriendly
Acknowledgements: The attached
white paper was written by Jim Ireland with substantial contributions
from Fuller Bazer, Lou DePaolo, Debora Hamernik, Mike Roberts, George
Smith, and Allen Tucker. The white paper’s contents were also
reviewed by Jeff Armstrong, Eric Antoniou, Janice Bahr, Nora Bello,
Jeannie Burton, Jose Cibelli, Judy Van Cleeff, Mary Delany, Brad
Fenwick, Ian Gray, Amy Iager, Mark Jutila, Fermin Jimenez-Krassel,
Harold Laughlin, Mark Mirando, Dawn Morin, Jack Odle, Vasantha
Padmanabhan, Guy Palmer, Joy Pate, Bob Petters, Karen Plaut, Jim Roche,
Peter Saama, Gary Williams, Eric Wong, and Xiangzhong Yang.
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