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4
Challenges Faced and Met in Research on
Food and Health
A panel of five university researchers reported on a wide variety of research
programs related to food and health, ranging from promising experiments to
proven treatments and from foods with healing properties to those carrying
pathogens. Panel members also addressed related issues, such as the importance
of collaboration and funding structures in advancing their research and what
they consider the most effective approaches for combating diet-related health
problems. Some panelists shared personal perspectives on developing research
programs that broke interdisciplinary barriers.
RESEARCH ENDEAVORS INVOLVING FOOD
Researchers described how some foods are being tested for their potential to
treat disease and others are being modified or fortified to enhance health.
Mushrooms, essential oils, and other foods are being used in studies to treat
cancer and other chronic diseases, they said. Corn has been modified to increase
its protein content, and eggs and milk have been fortified with omega-3 fatty
.
acre .s.
35
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36
EXPLORING A VISION
Food as a Curative
Harry Preuss, Professor of Physiology, Medicine, and Pathology at Georgetown
University Medical Center, began his career in internal medicine as a
nephrologist. Initially, he worked on sugar-induced hypertension. When he
found that chromium, as a nutritional supplement, circumvented that
mechanism, he became committed to exploring the food and health connection,
especially in preventive medicine and aging. Preuss pointed out that nutrition
and health issues were often considered in the realm of"alternative medicine," a
label that he questioned, saying, "Something works or it doesn't." He expressed
concern that consumer information on healthy diets presented mixed and
sometimes incorrect messages, and he felt that emphasis on counting calories
and exercise would be beneficial.
Preuss described his current research on the impact of foods such as
mushrooms, bitter melon, and essential oils, and nutritional supplements on
immune function, cancer, diabetes, and hypertension. He termed the findings
"possibilities," saying that more research is needed to prove definitively their
effectiveness. He noted that interest in the therapeutic effect of mushrooms in
treating cancer and immunologic disorders is growing. As an example, Preuss
offered preliminary results from one Asian study on the effect of maitake
mushrooms on rats with cancerous tumors, which suggested potential shrinkage
of the tumors, although he noted that the study was not a double-blind placebo-
controlled study, so the result would be of limited value. He added that an
extract of maitake and maitake powder have also been suggested by some to
diminish the side effects of chemotherapy, but "whether this turns out to be
something wonderful, we will have to see."
Preliminary results of tests with grislin (a fraction of maitake), bitter melon, and
a combination of the two to treat insulin resistance and hypertension associated
with diabetes were positive, Preuss said. He had found that the most sensitive
index of insulin resistance is a rise in blood pressure, and with treatment, blood
pressure went down in every case. Cinnamon, fiber, and chromium compounds
also can be effective in increasing insulin sensitivity, he noted.
Preuss said he has found that some essential oils are effective as bactericides and
fungicides. Two oils used in laboratory tests monolaurin derived from
coconut oil and the essential oil of oregano killed Staphylococcus,
Helicobacter pylori, and even anthrax. He suggested that oregano might also be
effective in killing Car~dida albicar~s and Escherichia colt. "There are things
that can be done with the foods that have little risk and can be helpful with
chronic disorders," he concluded.
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CHALLENGES FACED AND MET
Food Allered to Increase Nuiritive Value
37
Brian Larkins, Professor of Plant Sciences and Molecular and Cellular Biology
at the University of Arizona, described recent efforts to enhance the protein
quality of maize. He also discussed current laboratory work aimed at
understanding the molecular processes underlying the changes.
Some 9 to 10 billion bushels of corn are produced in the United States each year,
but this widely consumed cereal has relatively poor protein quality, he said.
Corn is especially low in lysine, an essential amino acid for humans and some
animals. Over the last few decades, researchers have been successful in altering
the protein composition of corn and increasing its lysine content. Early attempts
at protein enhancement resulted in corn with a soft, starchy texture that made it
susceptible to insects and produced "lousy tortillas," Larkins noted. However,
plant breeders, working with modifier genes, have created a mutant protein-
enhanced corn called Quality Protein Maize (QPM) that is very similar to
normal corn (see Box 4-1 for a more detailed perspective).
Larkins and his colleagues are studying the molecular processes and
mechanisms behind the success of QPM, trying to understand how the modifiers
work, how the mutation changes the lysine content, and the function of a process
called endoreduplication, which amplifies the number of gene copies when the
kernel is developing. They have determined that development of QPM is
closely related to the structure of starch, he said.
Larkins' laboratory goes beyond traditional cereal chemistry by looking at the
development of corn kernels, especially the synthesis of starch and storage
proteins. It has determined that part of the cytoskeleton network that surrounds
the endoplasmic reticulum can serve as an indicator of the lysine content, and
allows it to be used in selecting for increased protein quality. Larkins has also
linked the physical structure of starch grains in the endosperm to how high-
quality protein genotypes are developed.
Bruce Watkins, Director of the Center for Enhancing Foods to Protect Health
and Professor at Purdue University, and Adjunct Professor of Anatomy at the
Indiana School of Medicine, described various ways in which foods are being
altered to enhance their nutritional content and quality. He also described
current research in the use of nutraceuticals and phytochemicals to prevent or
correct medical conditions, such as osteoporosis and obesity.
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38 EXPLORING A VISION
Box 4-1. Quality Protein Maize (QPM).32
In 1963, three scientists at Purdue University discovered opaque-2 maize, a
mutant maize that was nearly twice as nutritious as normal maize and which
contained proteins. The discovery of the opaque-2 gene led many scientists to
believe that the protein deficiency that afflicts millions of people who depend on
maize as a stable food supply could be improved by adding the opaque-2 gene to
the world maize crop. However, the opaque-2 gene gives the kernel a soft,
starchy texture that caused the maize to be more susceptible to insects and to
break easily, and it could not be used to produce the same quality of food as
normal maize.
A team of maize scientists at the International Maize and Wheat Improvement
Center (CIMMT) in Mexico were able to develop what is now called Quality
Protein Maize (QPM), which has a greatly enhanced nutritive value, high yields,
normal moisture content, and good endosperm hardiness. In 2000, Surinder K.
Vasal, a maize breeder, and Evangelina Vilegas, a cereal chemist, shared the
World Food Prize for their efforts in developing QPM in the 1970s and 1980s.
Since 1996, CIMMT and other organizations have been able to strengthen QPM
breeding and promotion programs and have targeted developing countries that
use maize as a food staple. Norman E. Borlaug, Nobel Peace laureate and
president of the Sasakawa Africa Association, has strongly endorsed QPM
research and use through Sasakawa Global 2000, a program that has
successfully promoted QPM in Ghana and several other African nations.33
The Center for Enhancing Foods to Protect Health is a faculty-led organization
with a focus on advancing knowledge about food and how it affects health. It
has four research aims: discovery and methods development for health
protectants, such as phytochemicals and nutraceuticals; testing and validation of
health benefits, using primarily cell-culture and animal models;
precommercialization of functional food components introduced into traditional
food products; and molecular biology and food functional genomics. The center
is a collaborative effort involving faculty in the Schools of Agriculture,
Consumer and Family Sciences, and Veterinary Medicine at Purdue University,
and the School of Medicine, at Indiana University-Purdue University
Indianapolis (IUPUI), as well as scientists at other institutions. For example,
food scientists at the center are studying the feasibility of adding functional food
ingredients to bread formulation while making sure that it is visually appealing
32International Maize Testing Unit: QPM Background. 2003. Available online at
http://148.223.253.105/qpmbackground.htm [October 2003].
33For more information, see the National Research Council report, Quality Protein Maize. 1988.
Washington, D.C.: National Academy Press.
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CHALLENGES FACED AND MET
39
and maintains the usual qualities of white bread. The center, in cooperation with
other institutions and industry, has produced eggs fortified with omega-3 fatty
acids and conjugated linoleic acids, Watkins said. Researchers at the Center are
also exploring how diet can correct atrophy in muscle and bone tissue that
results from disuse, fractures, and space travel, and how nutraceuticals and
phytochemicals affect the differentiation of osteogenic stem cells.
The center has an educational component, with a special focus on middle school
through college, covering the origin of foods, how foods are processed, food
chemistry, and how nutrition affects health. Adult-education efforts include the
Phytochemical Learning Resource, which is available on the Internet and on
CD, to help nutrition educators and dieticians.
Watkins' research career exemplifies the kind of integration that is being
promoted for food and health research. He began his research career in animal
production and animal nutrition, investigating the role of probiotic bacteria in
gnotobiotic chicks to reduce enteric pathogens. He then moved on to biotin
metabolism and sudden death syndrome, characterization of abnormal bone
growth in nutrient deficiency, food lipids and the chemistry of functional food
ingredients, molecular and physiologic actions of phytochemicals on cell
function and bone biology, and nonembryonic stem-cell research in bone health.
Food as Potential Pathogen
Two panel members discussed the other side of food and nutrition: its potential
to harm rather than nourish or heal. Linda Saif, a Professor at the Ohio
Agricultural Research and Development Center of the Ohio State University,
discussed her research on enteric calciviruses that affect animals and humans,
including the Norwalk virus that has caused outbreaks of stomach illnesses on
cruise ships and in other settings. Susan Sumner, head of the Department of
Food Science and Technology at Virginia Polytechnic Institute and State
University, addressed the impact of globalization of the food supply, the use of
food as medicine, and the potential of food as an agent of bioterrorism.
Saif reported that foodborne infections in the United States cause about 76
million illnesses each year, account for about 325,000 hospitalizations and 5,000
deaths each yearn, and have an estimated annual cost of $23 billion.35
34 Mead, P.S., Slutsker, L., Dietz, V., McCaig, L.F., Bresee, J.S., Shapiro, C., Griffin, P.M., and
R.V. Tauxe. 1999. Food-related illness and death in the United States. Emerging Infectious
Diseases. 5:607-625.
35 Hedberg, C. 1994. Changing epidemiology of food-borne disease: A Minnesota perspective.
Clinical Infectious Diseases. 18:671-682.
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40
EXPLORING A VISION
Noroviruses (caliciviruses) cause an estimated 67 per cent of the known cases if
foodborne illness. Outbreaks associated with those viruses have occurred on
cruise and military ships and in other institutionalized settings, such as schools
and nursing homes. About 40 percent of the outbreaks are thought to be the
result of foodborne infections, but the infections can also be waterborne.
Saif and her colleagues have tried to address some of the impediments to
working with noroviruses. They adapted a porcine enteric calicivirus to grow in
cell culture by using novel methods and they are now using it as a model to try
to grow human enteric caliciviruses (noroviruses and sapoviruses). The
researchers also used primers originally developed to detect human caliciviruses
to detect animal caliciviruses; with sequence analysis, they discovered that the
two groups of viruses are genetically similar. Recently they developed an
infectious clone of a porcine enteric calicivirus that they hope to use in studying
the molecular basis of the virus's virulence and cell adaptation. Current
research at the university focuses on determining how the viruses cause diarrhea
in host species and how the infections can be prevented by using pigs and craves
as animal models for sapoviruses and noroviruses similar to those that infect
humans. Researchers, including those in Saif's laboratory, are using
bioengineering to develop noninfectious calicivirus-like particles for use in
vaccines and are trying to determine the origin of strains of the virus that affect
humans particularly to see whether they are zoonotic. Enteric caliciviruses
and coronaviruses are among a large number of emerging pathogens that are
believed to be zoonotic. Saif singled out the SARS coronavirus as one example
of the harm that such pathogens can cause.
As a food microbiologist, Sumner identified food safety, food bioterrorism, a
global food supply, and the use of foods as medicine as issues of importance.
She discussed several unanswered questions that should be investigated further,
regarding the risk that the United States faces from a food-related bioterrorist
attack: How great is the risk? What types of foods are the most likely targets?
What segments of the population are at greatest risk? Sumner was also
concerned about the preparedness of the food producers and processors to deal
with the intentional introduction of pathogens and toxins that would normally
not be found in foods and that cannot be controlled with the usual food-safety
practices.
Consumers expect food to be processed the same, to have the same high
nutritional quality, and to be equally fresh and safe, regardless of where it is
produced, Sumner explained. However, globalization raises serious concerns
about food safety, she continued, citing as one example fears about mad cow
disease associated with beef products from the United Kingdom and, more
recently, Canada. New food-processing techniques are being developed and
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CHALLENGES FACED AND MET
41
used, but how they affect the safety and nutritive value of foods has yet to be
determined, she said. Questions remain about the tradeoffs between fresh and
processed foods which is better from a nutrition standpoint versus a safety
standpoint, and what are the best ways to strike a balance between fresh and
processed foods. As with the baby-food and pet-food industries, food products
are going to be targeted for development for specific health-related features,
both in terms of food safety and of chronic disease.
Collaboration
Several panel members stressed the importance of collaboration across
disciplines, agencies, and institutions to foster better research and education in
food and health. They also stressed that funding agencies should establish or
increase funds aimed specifically at cross-sectional research and that institutions
should change their reward structures to support collaboration.
Using calicivirus research as a model, Saif identified four essential components
for integrated research programs: funding, collaboration, infrastructure, and
graduate students and postdoctoral fellows. Establishing a broad funding
foundation by breaking out veterinary, food-safety, and human-health
components of her research program has allowed her to obtain funding from
USDA, EPA, and NIH. Saif added that timely availability of visas for top
international students and postdoctoral fellows is also essential: severe visa
restrictions may jeopardize our globally competitive scientific research
programs and may limit participation by international scientists in U.S. scientific
meetings, thereby weakening both U.S. and global scientific research.
Saif stressed the importance of collaboration among veterinary, agricultural, and
biomedical scientists in studying foodborne pathogens and other disease agents
suspected of originating in animals. This reminded listeners that, of 156
emerging diseases, almost three-fourths are zoonotic,36 and more information is
needed about them in the natural hosts. For example, biomedical researchers
only recently recognized that coronaviruses, which cause colds and other
respiratory illnesses in humans and were responsible for the recent outbreak of
SARS, have caused respiratory and enteric diseases in animals for many years,
she said. Closer ties between animal and medical scientists could facilitate
research into how those diseases are spread, but more support is needed to
encourage such collaboration. She suggested that although USDA and NIH
grants support basic research, sometimes bridging or targeted competitive
36Levy, Stuart B. 1996. Microbial threats and the Global Society. Emerging Infectious Diseases.
2(1): 62-63. Available on-line at ~df [January
2004].
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42
EXPLORING A VISION
grants, especially in comparative medicine, are needed to develop specific
diagnostics and vaccines for emerging animal diseases and animal reservoirs of
human diseases and or to assess and control food-borne pathogens.
Both the administrative and investigative components of research infrastructure
are being taxed as many universities are changing from state-supported to state-
assisted, Saif said. Grants-management offices and long-term technical support
from universities are important for developing successful integrative research
programs, as are facilities to study infectious animal, plant, and human
pathogens, including bioterrorism agents. Without highly qualified national and
international graduate students and postdoctoral fellows to carry out and carry
on research, these programs would not succeed, Saif added.
Nancy Lewis, Associate Professor of Nutritional Sciences and Dietetics and
Chair of the Interdepartmental Nutrition Graduate Program at the University of
Nebraska, described her career as a microexample of integration in this case,
of nutritional biochemistry with nutrition behavior.
The Interdepartmental Nutrition Program is the University of Nebraska's
primary doctorate program in human nutrition, includes faculty in food science
and technology, in animal science, and in the Department of Nutritional Science
and Dietetics. To incorporate health behavior, a faculty member of the
Psychology Department who is interested in health behavior change has recently
been recruited, Lewis reported. With the added expertise, the program is better
able to serve the needs of students interested in nutrition behavior. A continuing
challenge for the program is meeting the graduate education and research needs
of practicing dieticians, who provide the university with invaluable connections
to the health-care environment. As practitioners working full-time in nutrition
therapy, they are interested in enhancing their clinical skills, their understanding
of science, and their level of practice. One creative solution has been to develop
courses for distance delivery, so that students do not have to be on campus to
meet all their educational needs. That solution will not, however, solve
problems of residency requirements or of availability of research facilities. The
agriculture and food and health connection can be strengthened by working with
clinicians, determining and meeting their needs, Lewis said. As several panel
members pointed out, collaboration is often closely aligned with funding,
making it very difficult for one to occur without the other.
Lewis also discussed the multistate research committee on omega-3 fatty acids
called NC-1167 (Committee on N-3 Polyunsaturated Fatty Acids and Human
Health and Disease) as an example of improving interdisciplinary research.
Initially, the committee members had a nutritional-biochemistry perspective. By
recruiting additional committee members who shared her interest in nutrition
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CHALLENGES FACED AND MET
43
behavior, she was able to incorporate this perspective into the committee's
discussions and research planning. It has been successful in working with the
Nebraska Heart Institute on behavioral interventions, and Lewis suggested that
grant proposals requiring such integration as she has experienced, including
biochemical, behavioral, and outreach or continuing-education components,
would be very valuable.
Larkins addressed factors that he believed contributed to his success in obtaining
support. His research has been supported by several federal agencies, including
the USDA's National Research Initiative (NRI), the Department of Energy's
Energy Biosciences Program, and NSF, as well by industry sponsors. He
concluded that his work had appeal to both the public and private sectors
because some aspects have practical applications and others involve
fundamental molecular genetics, molecular biology, and cell biology. His
multidisciplinary approach was also attractive to students from a variety of
backgrounds. He qualified his success by adding that if he had tried to support
his research on the basis of nutrition, he probably would not have gotten any
funding, and his diverse funding sources demonstrated that food and health
research is not the primary interest or responsibility of any one agency.
Larkins pointed out that the structure of research funding presented challenges
to traditional food and health research: the average funding from USDA's NRI
is about $60,000 per year for two years. That requires that the grant-renewal
process begin in the second year of the initial grant. He contrasted that with
NIH's average level of research funding: $250,000 per year for four years, not
including indirect costs. He noted that agencies are more willing to fund
research on organisms that can be raised in laboratories or growth chambers,
such as yeast or Arabidopsis, which is relatively inexpensive and more easily
justified, and less likely to fund research on crop plants, such as corn, wheat, or
soybeans, which is more labor-intensive. He also noted that there has been a
substantial reduction in institutional support, especially in Colleges of
Agriculture, for research infrastructure.
SOLUTIONS TO FOOD-RELATED HEALTH PROBLEMS
Responding to a question about which technologic solutions or approaches are
likely to have the most immediate effect on food-related health issues, Watkins
zoned in on approaches that increase dietary intake of good fats and reduce
harmful fats; this is an opportunity for developing new and better food-delivery
systems. He mentioned that omega-3 fatty acids are a crucial nutrient for
avoiding deficiencies and optimizing health. NIH studies indicate that omega-3
fatty acids can have dramatic effects on health, possibly even on psychiatric
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44
EXPLORING A VISION
disorders, he said. However, most consumers are not getting the recommended
amounts of omega-3 fatty acids in their diets, because they do not eat sufficient
quantities of fish and edible oils high in this nutrient, Watkins cautioned. This
underlines the importance of making the nutrient available in a broader array of
foods, he said, noting that just last year FDA approved the use of DHA, an
omega-3 fatty acid, in infant formulas. Technologies that reduce harmful fats in
the diet are also crucial for better health, he added. They include changing how
vegetable oils are processed, modifying plants that produce edible oils, and
reducing the content of animal products.
Looking to the future, Watkins envisioned a directed approach to food
development: products would be targeted to a person's age, gender, and genetic
makeup. He highlighted the opportunities presented by the Human Genome
Project: new food products could be developed that lower risk of chronic disease
through an understanding of how those components in foods modulate genes
and protein expression. Other opportunities are the development of food
components that work with drugs as drug synergists to address issues of
cardiovascular disease or decreasing inflammatory response; bioactive
ingredients, nutraceuticals and phytochemicals; and proteins, such as antibodies
that are produced from plants. As the food supply evolves, Watkins predicted
lower health-care costs, better nutrition, new medical and functional foods,
delayed onset of disease, and improved quality of life.
Sumner took a broad view of the role of food in health, with the convergence of
such issues as food science, nutrition, food safety, diet, chronic disease, and
medicine. She envisioned an integrated, multilevel approach, targeting specific
populations. Sumner applauded the rich tradition of collaboration between
agriculture and life sciences, but she pushed for increased collaboration with
medical and veterinary colleagues.
Sumner cited the example of the Virginia Tech food and health initiative,
involving the Department of Food Science and Technology, the Department of
Human Nutrition, Foods and Exercise, and the Center for Food and Nutrition
Policy. She challenged scientists to consider how a specific research objective
can fit into a bigger picture that may open up new opportunities and questions in
food and health. She also called for better communication with consumers and
regulators, who may be looking for a quick solution to a health problem that has
taken years to develop.
Representative terms from entire chapter:
food science
