"The purpose of medicine is to prevent significant disease, to decrease pain
and to postpone death when it is meaningful to do so. Technology has
to support these goals - if not, it may even be counterproductive."

-Dr. Joel J. Nobel, co-founder, Emergency Care Research Institute, 1985

Although Florida International University does not have a medical school, for years the University has been conducting extensive activities in the health arena. FIU's mission statement affirms that the University will "solve critical health, social, educational, and environmental problems through applied research and service" - and that declaration helped provide the impetus for Health to be designated as one of its five priority academic strategic themes (along with International, Environmental, Urban, and Information) in the University's strategic plan, "Reaching for the Top."

Today, more than 150 faculty staff health programs in the medical sciences - anatomy, biochemistry, microbiology, nutrition, physiology, psychology, biomedical engineering - and the related health fields of dietetics, public health, nursing, gerontology, health services administration, medical laboratory sciences/clinical pathology, health information management, occupational therapy, social work, and medical sociology/anthropology. In addition, faculty from other departments are playing an active role in projects concerning health.

"Health-related research is a growing area at the University," said Tom Breslin, vice president of Research and Graduate Studies. "To date, most of this research has been centered around four broad areas: immunology, bioengineering, dietetics and nutrition, and public health. We'll see further development in those areas as well as growth in other areas as we formalize the University's health research program." During the 1997-98 academic year, FIU attracted $1.34 million in health-related research funding from a wide variety of public and private sources - and all indicators point to continuing increases in such funding.

"FIU is well positioned to address major health issues facing our nation today and in the 21st century," said FIU President Modesto A. Maidique. "The University is playing a leading role in training professionals who provide health care and shape health care systems. In addition, through our research programs, we are contributing to the scientific breakthroughs that will dramatically improve the health and well-being of future generations."

Faculty throughout the University are engaged in basic and applied research that are making these medical breakthroughs possible. The three following projects are representative of the state-of-the-art health research being conducted at FIU.

Food for the eyes
Remember as a child when your mother begged you to eat your broccoli and spinach, insisting that they were good for you?

She was right - and it wasn't just for the vitamin A and C or iron they provided. According to two FIU researchers, two substances contained in green, leafy vegetables and yellow vegetables and fruits (such as corn and apricots), may help protect the eye from developing age-related macular degeneration (AMD), the leading cause of vision loss in the U.S. The irreversible disease afflicts 20 percent of people over the age of 65 and 35 percent of those over 75.

For the past 15 years, Richard Bone, professor of Physics, and John Landrum, associate professor of Chemistry, have collaborated on research on the macular pigment and its possible connection with the eye disease.

The macula is the portion of the retina (approximately five millimeters in diameter) that is responsible for the central part of the visual field. The central part of the macula is distinguished by its yellow coloration, the "macular pigment." Despite its small size, this region of the retina is endowed with the highest degree of visual acuity.

For two centuries, the composition of the macular pigment had remained a mystery. Francesco Buzzi, an ophthalmic surgeon, discovered in 1782 that the central part of the retina was marked by a yellow spot. George Wald, 1967 Nobel Laureate in medicine, postulated the macular pigment was composed of lutein and he proved the carotenoid nature of the pigment.

Until the 1980s, though, it was not known with certainty what substances constituted the macular pigment. That is, until professors Bone and Landrum met at FIU, discovered they shared common research interests and developed their collaboration.

"I'd been working on the macular pigment and was interested in its effect on vision," said Bone, a biophysicist.

"I was studying its ability to render the eye sensitive to polarized light. ...When I met John and told him, 'Nobody really knows what this pigment is,' John told me that's what chemists do. We've been collaborating ever since," commented Bone. "It's a multidisciplinary collaboration, and each of us has had to learn from the other."

In a paper published in 1985, Bone and Landrum revealed that the human macular pigment is composed of lutein and zeaxanthin, two pigments that are found in many vegetables and fruits.

"We now know it's composed exclusively of these two carotenoids," Landrum said. "The high concentration of these two carotenoids is one of the surprising features of the macular pigment. This is evidence that the macular pigment is functionally significant."

Recent research has focused on further analysis of the pigment, its relationship to AMD, and its absorption, transport and metabolism.

As they delved further and further into their research, the two professors became more and more convinced of the macular pigment's importance in protecting the retina. "The macular pigment's ability to absorb blue light is probably its most important ability," Landrum noted, "but it may also function by directly deactivating extremely reactive singlet oxygen generated in the retina by blue light."

More than a decade of research led up to the studies Bone and Landrum have been conducting the past two years. Based on evidence suggesting the protective role of the macular pigment - and research noting an association between a particular type of macular degeneration and a diet low in lutein and zeaxanthin - they wanted to address two related issues: Do lower than normal levels of macular pigmentation represent a risk factor for the development of AMD? Can dietary supplements of lutein and/or zeaxanthin increase pigment levels in the macula, thereby providing additional protection against AMD or slowing its development?

To answer the first question, they compared the macular pigment of normal and AMD donors, which seemed to support the hypothesis: the lowest levels of macular pigment were found more frequently in the eyes of donors having the disease.

"AMD is a multifactorial disease," said Bone, "and it appears that low levels of macular pigment may constitute one risk factor."

To study the second issue, Bone and Landrum ingested a lutein supplement daily for 140 days; over the course of the experiment and thereafter, the level of lutein in their blood was measured as well as changes in the level of their macular pigment. To measure the pigment, Bone developed an instrument called a heterochromatic flicker photometer. Once again, their hypothesis was confirmed. Although it appeared to be a slow process, after 140 days of lutein supplementation there was a 20 to 40 percent increase in the pigment level. This increase reduced by 30 to 40 percent the amount of blue light reaching the tissues which are damaged in macular degeneration. Their research also revealed that while lutein and zeaxanthin are transported into an individual's retina in the same proportions found in blood serum, much of the lutein is converted into meso-zeaxanthin, a unique nondietary form of zeaxanthin. This metabolic conversion is important evidence of the physiology of the macular pigment.

The data Bone and Landrum obtained, as well as that of others, suggests that macular pigment does protect the retina; lower pigment levels could contribute to the more rapid development of characteristics associated with AMD. In addition, long-term lutein supplementation can significantly increase the level of pigmentation within the macula. They are currently conducting a six-month study with 24 volunteers - funded by the Rehnborg Center for Nutrition and Wellness - to determine the effect of a lutein-containing supplement on macular pigment density.

Bone and Landrum have received some $700,000 in external funding for their research on the macular pigment, mostly from the National Institutes of Health. The National Eye Institute and the Food and Nutrition Board of the National Academy of Sciences are interested in their current work; they are considering whether a RDI (Reference Dietary Intake, comparable to the Recommended Daily Allowance) should be established for lutein and zeaxanthin.

"Lutein or zeaxanthin or both may be recognized before long as essential nutrients for the continuing health of the eye into old age," Bone said. "There's more that needs to be done, but it's good to have had the opportunity of providing a significant contribution to our knowledge of these compounds."

"Our research began with a modest project to identify what was considered an insignificant feature of the retina," Landrum said. "The results of our study of the macular pigment have surprised us several times over the years. We hope that our current efforts can further clarify the role of macular pigment in the disease process of macular degeneration."

Better health through engineering

In recent years, South Florida has become a hotbed for technology development in biomedical engineering. The tri-county area (Miami-Dade, Broward, Palm) has more than 890 biomedical firms employing 19,000 persons; Miami-Dade County ranks eighth among U.S. counties for employment in the medical devices industry; and Florida ranks third among U.S. states with 1,089 health technology firms.

To capitalize on this opportunity, earlier this year FIU established the Cardiovascular Engineering Center (CVEC), a multidisciplinary unit in the College of Engineering that brings together academia, industry and clinical medicine to advance cardiovascular science and technology. Though this union, the center intends to increase the speed and effectiveness of the transfer of basic and applied research to practical applications in clinical medicine. The CVEC also provides biomedical engineering education and training at all levels, ranging from precollege to postgraduate to professional. The research of two members of the Mechanical Engineering faculty, Richard Schoephoerster and James Moore, constituted the foundation of the center, and the two of them recognized the potential of creating the interdisciplinary unit.

Last July, the state Board of Regents approved a master's program in biomedical engineering for inclusion in the University's five-year plan; it is hoped the program will be launched in fall 1999. The CVEC serves as the heart of FIU's biomedical engineering program, which is designed to prepare graduates for careers in the industry. The CVEC faculty reflect its interdisciplinary approach; they are drawn from the Electrical and Computer, Industrial and Systems, and Mechanical Engineering departments of the College of Engineering, as well as the Department of Biological Sciences (in the College of Arts and Sciences) and the College of Health Sciences.

Research at the CVEC, which ranges from basic to applied, focuses on the design, development and enhanced implementation of diagnostic, interventional, therapeutic, and replacement systems and devices associated with the cardiovascular system and the transport or analysis of blood. Research has been conducted in areas including: biofluid and biosolid mechanics; experimental, mathematical and computational modeling; biomaterials; artificial heart valves, cardiovascular devices and instrumentation; computer vision, bioimage and signal processing; and diagnostic imaging.

For example, the research of CVEC director Schoephoerster focuses on the effects and mechanics of blood flow. His major research projects have examined:

• the effect of blood flow on coagulation, the ways in which coagulation can cause thrombosis, clotting of artificial heart valves, and the dangers of blood coagulating with other artificial biomedical materials
  
  
• the hydrodynamics of artificial heart valves: how well they're made and how well they function
  
  
• a computational model of blood flow in the heart to enable a more accurate assessment of heart function.

"The creation of the center was a dream of mine since I got here (to FIU) in 1990," said Schoephoerster. "We thought it was important to develop partnerships with local industry and clinicians. This will not only help our research program, it will help our students, who will work on master's research projects with our industry partners. It will also help industry by furnishing graduates trained in the field."

Moore, the other founding partner of the center, has conducted research which focuses on the mechanics of the cardiovascular system and the interaction with the biological tissues which make up the arterial walls. Three primary projects have emerged from this interest:

• the mechanical factors that cause atherosclerosis - hardening of the arteries, the leading cause of morbidity and mortality in industrialized nations - may be linked to the disease's localization in four specific locations, usually the neck or the arteries around the heart. Research has concentrated on two forms of "stress" the arteries are subjected to, the ways in which they effect the cells and how these processes lead to the formation of atherosclerosis
  
  
• quantify the blood flow patterns in the coronary arteries to better understand how mechanical factors are involved in atherosclerosis formation
  
  
• analyzing changes in blood flow patterns created by the placement of stents in arteries and developing new stent designs to alleviate these flow disturbances. Moore has filed a patent application for a new stent he designed.

"In order to develop work in this field, it's essential to collaborate with medical doctors, biologists and other scientists," Moore commented. "These collaborations provide a valuable perspective on one's work."

Other CVEC faculty and their research specialties include:

• Malek Adjouadi (Electrical and Computer Engineering) - computer vision, image analysis, pattern recognition
  
  
• Armando Barreto (Electrical and Computer Engineering) - biosignal processing, EEG feedback
  
  
• Rene Herrera (Biological Sciences) - molecular biology, gene expression and mapping
  
  
• Rainer Schmitt (Electrical Engineering; director, Fraunhofer Technology Center) - ultrasonic imaging and system design, transducer design and manufacturing, biomedical instrumentation
  
  
• Patrick Shen (Medical Laboratory Sciences) - hematology, medical laboratory instrumentation.

The center also recently hired a research coordinator to act as a liaison between faculty/students and industry and is in the process of recruiting two additional faculty members.

The interdisciplinary, collaborative nature of the CVEC, as well as the partnerships it has forged with South Florida companies and organizations, complements and reinforces the center's strength and potential. Partner organizations (which have the described biomedical specialties), are also represented on the CVEC Advisory Board:

• Althin Medical Inc. - artificial kidney and dialysis machines
  
  
• Baptist Health Systems - Baptist Hospital and the Miami Vascular and Cardiac Institute
  
  
• Beckman-Coulter Corporation - automated hematology analysis
  
  
• Boston Scientific Corporation (Symbiosis Division) - surgical instruments
  
  
• Cordis Corporation (a Johnson & Johnson company) - cardiovascular interventional products
  
  
• Corvita Corporation (a Pfizer company) - vascular grafts and biomaterials development
  
  
• Fraunhofer Technology Center - university-industry biomedical technology transfer.

In November, the College of Engineering was awarded a $1 million grant from the Whitaker Foundation, which is dedicated to improving health through the support of biomedical engineering. Based on the CVEC and its alliance with industry partners, the funding will be used to establish a Biomedical Engineering Institute at FIU.

The partnership with Baptist Hospital has been particularly close and offers a promising prospect: it may conduct clinical trials to test the findings and technology developed at the CVEC.

"Baptist and its Vascular and Cardiac Institute make for a good partnership," Schoephoerster said. "We envision a team approach where they will come to us with ideas. Their doctors are also interested in basic research, which is an environment they don't have."

In addition to collaborative research, FIU biomedical engineering students will rotate through a variety of clinical areas at Baptist applicable to their research and thesis subjects.

"We hope in the next few years this partnership will be even more collaborative," said Dr. Jack Ziffer, director of cardiac imaging at Baptist's Miami Vascular and Cardiac Institute. "It offers benefits for both FIU and Baptist.

"We offer the potential opportunity to apply basic research in a clinical environment and we can provide insight into areas that are clinically important and help the relevance of FIU's research efforts. And we get to learn about new developments in engineering and science that may ultimately help patients. ...In a sense, ultimately we can function as a combined entity - a medical school without the medical students, with researchers spanning the gamut from basic to clinical science."

Secrets from the deep

In the early 1500s, Ponce de Leon searched in vain throughout Florida and the Caribbean for the fabled "fountain of youth." But if he was on the scene four centuries later, the explorer might have found clues to the secret he sought in a laboratory in the Perry Building at FIU-University Park. That's home base for a veteran FIU microbiologist and immunologist who is hot on the research trail - a journey that has led her from the lab to the sea.

Sylvia Smith, professor of Medical Laboratory Sciences who has been at FIU since 1974, has spent 20 years studying the extraordinary immune system of sharks. Given the hearty nature of sharks and their phenomenal longevity as a group, perhaps it's not surprising that they may hold some medical secrets. Sharks are among the most ancient surviving animals on earth, dating back some 350 million years and predating all teleosts or bony fish. Sharks have no bones, their skeletal structures being all cartilage. What's more, they're a remarkably healthy group, and have gained a reputation for being virtually tumor-free.

"They're very primitive, they've survived for a very long time and their immune system is definitely an integral part of their success," Smith said. "What better than to study the immune system of an animal with such impressive resilience to viral infection and tumor growth - their record shows that they must be doing something right!"

Smith's interest in sharks developed from her studies in microbiology and immunology, the fields in which she received her undergraduate and graduate degrees. Her early research focused on bacteria resistant to antibiotics, specifically erythromycin-resistant streptococci, which can cause scarlet and rheumatic fevers - sicknesses contracted by her and her mother.

Her later studies with Georg Jensen, who carried out pioneering research on the shark complement system, the proteins in blood serum which carry out immune function, led to her continuing interest in this complex aspect of the immunology of these sea creatures. She has been carrying out her federally funded research using techniques of molecular biology in her laboratory at FIU, to analyze blood samples obtained from eight nurse sharks kept at the Keys Marine Laboratory in Long Key. Her studies have led to collaboration with colleagues at St. Andrews University, Scotland, Oxford University, England, and the universities of Tokyo and Kyushu, Japan.

Last year, Smith launched a study of sharks' antibacterial peptides, proteins that fight bacteria. "These could well prove to be of medical significance," she noted, "if we can identify molecules or molecular structures that can be used as blueprints to produce a product effective against bacteria, especially against those resistant to run-of-the-mill antibiotics in common use. We've already been able to identify shark substances with these antibacterial properties."

Her other major research pursuit, which she initiated about three years ago, evolved from a conservationist concern: the decimation of shark populations due to consumer demand for shark cartilage. The use of this preparation, a food supplement made from the powdered cartilage of sharks, has become very popular due to its alleged health benefits.

"No study has definitively proven that shark cartilage does, in fact, cure any specific medical condition," Smith said. "We expected to show that shark cartilage doesn't do anything." Much to her surprise, it appears that the opposite is true. She found that commercial shark cartilage can induce a "tumor necrosis factor (TNFa)," which is known to help control the development of some tumors. Other studies have shown that preparations of mammalian cartilage can inhibit angiogenesis - the ability to generate new blood vessels - which restricts the growth of tumors.

"We need to be cautious about interpreting the potential pluses," Smith warned, adding that she would like to conduct clinical research on the effect of shark cartilage. "As yet, we don't know enough about it and that worries me. We need to know much more. Many people are taking shark cartilage and they don't have a clue what it's doing. What is its short- or long-term effect on normal immune function? Does it compromise our system in the long run?

"I want to learn more about how our innate immunity protects us. What role does immunity play in our survival? That's why I became interested in the shark - because it has survived so beautifully."