Report on research

              Editorial inquiries and comments: Editor, Report on Research: UA News Services The University of Arizona Tucson Arizona 85721 (520) 621-1877 dsaintg@ccit.arizona.edu Report on Research Staff Director of Research Communications Charles A. Geoffrion cgeoff@ccit.arizona.edu Editor Dennis D. St. Germaine Manager, University Publications UA News Services Director of Distribution Alice Langen aclangen@ccit.arizona.edu Director of Photography Diane Joy Schmidt Art Director Rita Ellsworth AHSC Biomedical Communications Writers Nancy Guthrie AHSC Public Affairs Lori Stiles UA News Services Judy Elam AHSC Public Affairs Dennis St. Germaine







The University of Arizona Tucson, Arizona Summer-Fall 1995 Volume 11, Number 2







CONTENTS



Introduction







RESPIRATORY SCIENCES



Toward Breathing Easy: Long-Range Study Targets Respiratory Diseases Community Responds with Enthusiasm to Study Searching for Clues to What Causes Asthma UA Researchers Target Onset of Asthma Searching For New Ways to Treat Asthma Keeping Exposure to a Minimum Helps Asthma, Allergies Healthy Children Help Researchers Study Illness Sleep Apnea Sufferers Risk Heart Disease







UA News Services George Humphrey AHSC Public Affairs Kate Maguire Jensen AHSC Public Affairs







WORK IN PROGRESS



Universe is 'Awash With Dim Galaxies'







TEACHING AND RESEARCH



Jean Spinelli AHSC Public Affairs Jordan Gruener AHSC Public Affairs Arizona Board of Regents Eddie Basha, President George H. Amos III Rudy Campbell Art Chapa Judy Gignac Andrew Hurwitz John F. Munger Douglas J. Wall Mark Davis, Student Regent Ex Officio Fife Symington Governor of Arizona Lisa Graham Arizona Superintendent of Public Instruction HTML Design Ryan Clark







Independent Study Binds Teaching to Research







PREVIEWS & POSTSCRIPTS



DIRECTORY OF RESEARCHERS







Report on Research On Line



This issue of Report on Research is being published at a time of significant transition in America. For the past half century our nation has led the world in discoveries as a result of basic research in all fields of the sciences, especially medical, biological, physical and social-psychological. The majority of this work has come as a result of the funds made available from the National Institutes of Health and the National Science Foundation. These are the major tax supported agencies of our federal government that provide resources and leadership to the direction of research activities in America and many other nations. This same period has been characterized by a flourishing of creative activity in the arts and letters with similarly based support from the National Endowments. As this century comes to a close we now witness a trend among many citizens and political representatives to cut back significantly from current levels of funding. Various plans are under consideration. All would level or cut dramatically the amount of funds that underwrite progress in the largely university-based research and creative activities, which have contributed so greatly to the quality of life now enjoyed by Americans and many others. The great research universities across our land, The University of Arizona (ranked no. 18) among them, are at risk in their efforts to continue to serve the national agenda. America's world leadership in this area depends entirely on our capacity to maintain technical superiority and produce a continuous stream of workers well trained in a broad array of specialties. Perhaps the best example can be found in the rapidly expanding multibillion dollar biotechnology industry which is highly dependent on a steady supply of both new knowledge and skilled personnel. A research area in which The University of Arizona has played a premier role is that of respiratory sciences. As a result of 30 years of leadership by Professor Benjamin Burrows, Chalfant-Moore Professor of Medicine and Director of the University's Respiratory Sciences Center, this program has become one of our nation's leading sources of research findings in support of the improvement of our understanding and treatment of such chronic diseases as asthma, emphysema, and bronchitis. Soon after joining the faculty, Dr. Burrows founded and raised the funds needed to construct the Respiratory Sciences Center. Dr. Burrows led the team that crafted the first successful proposal for the National Institutes of Health multimillion dollar funding to establish specialized centers of research. This SCOR program has been funded for over a quarter century and began an epidemiology program focused on elucidating the causes and natural history of airwaysobstructive diseases. This world-renowned program continues today as the longest continuously funded SCOR grant in airways-obstructive







Michael A. Cusanovich and Charles A. Geoffrion







diseases. More than three thousand Tucsonans were recruited into this study in 1970 and have continued their involvement to this day. Dr. Burrows is internationally recognized for his contributions to our current understanding of the pathogenesis, course and treatment of airways-obstructive diseases. Dr. Burrows has determined or directed the efforts which led to demonstrating that lung function abnormalities in adults have their roots in abnormal lung function detectable in childhood; determining which lung function tests can and cannot be used to help delineate the major categories of airways diseases; and characterizing a distinct syndrome, asthmatic bronchitis. He has characterized the impact of smoking on lung function and linked smoking to immune system alterations. Most recently he and his colleagues have described how the prevalence and patterns of chronic airways diseases change with age and gender, provided substantial evidence that all asthma may well be critically linked to the class of antibodies referred to as IgE, and identified a strong index of suspicion that exposures to allergens in early life, maybe even in neonatal life, impact the subsequent development of asthma. Dr. Burrows remains warmly regarded as mentor, teacher and friend to many trainees, and revered clinician to many patients. His founding directorship of the Respiratory Sciences Center will always be a continuing inspiration to faculty, students and trainees. How do we put a dollar value on the results of research that have improved the lives of so many people, as in the case of Dr. Burrows and his colleagues What are the savings on medical care costs in terms of money not spent as a result of this progress If universitybased laboratories can no longer pursue the basic research that leads to this progress, then who will Private industry confines itself to more applied levels of research and specific product development. What do we lose as a people if our citadels of basic learning, the research universities, can no longer operate at the forefront of knowledge Michael A. Cusanovich Vice President for Research and Graduate Studies Charles A. Geoffrion Associate Vice President for Research







Toward Breathing Easy: Long-Range Study Targets Respiratory Diseases



When two physicians and a scientist decided to apply for a national research grant to study airways obstructive diseases in 1971, no one realized that they were embarking on a relationship that would last nearly 25 years. Certainly no one anticipated the scope of the project which would involve more than 5,000 people of all ages from 1,650 households, representing a wide range of socio-economic groups. Nor did they realize that a host of other studies would result from this one successful research activity. Benjamin Burrows, M.D., Director, Respiratory Sciences Center, with the American Thoracic Society Scientific Accomplishment Award he received in May 1995. It was 1968. Arizona had just built its only College of Medicine at The University of Arizona in Tucson. The new medical faculty included dynamic physicians and basic scientists who were determined to build a national reputation for a fledgling college that would one day achieve success in many areas. Dr. Benjamin Burrows, recruited from Chicago to head the Section of Pulmonary Diseases, was well known as a respected pulmonologist and intensely dedicated to understanding lung disease. He soon discovered that Tucson was fertile ground for chronic obstructive lung diseases-- twice as prevalent in the Old Pueblo as in the rest of the nation. But chronic bronchitis and emphysema were growing at alarming rates elsewhere in the country and there was much interest in the causes, origins and natural histories of these disorders. The National Institutes of Health (NIH) announced multimillion dollar funding for "specialized centers of research" (SCOR) to study obstructive lung diseases at various sites. To submit an application for the grant, Burrows organized a team that included biostatitician and epidemiologist Michael Lebowitz and pulmonary physiologist Ron Knudson. "When the (NIH) team arrived for a site visit, all they saw was the basic sciences building and a big hole in the ground where the hospital was being built," Burrows says. "We were flabbergasted when they told us we got the grant." Five centers in the nation received funding over a five-year period to study the causes of asthma, emphysema and chronic bronchitis. The UA College of Medicine was one of them. This led to the creation of the respiratory sciences division, and soon after, the Respiratory







Sciences Center, the first of seven Centers of Excellence at the College of Medicine. Those early days were exhilarating for the young investigators, but they soon realized they would have to bring in specialists who were knowledgeable in other areas. Pediatricians, radiologists, immunologists, pharmacologists, nurses, computer scientists and experts from many other disciplines were recruited to the team. "Our goal was to go beyond the treatment of end-stage lung disease to discover and understand the origins and development of airways disease," Burrows says. The Respiratory Sciences Center, a world-class research facility, is now famous for its multidisci-plinary approach to the study of lung disease. Called a "national resource" by reviewers appointed by the National Institutes of Health, "The Tucson Epidemiological Study of Airways Obstructive Disease (AOD)" provided a basis for formulating health policies and practices regarding lung disease.







Principal co-investigator Lebowitz compares the study's impact on lung disease with the famous Framingham, Mass. study of heart disease, now in its 35th year. Just as cholesterol, smoking and high blood pressure became identifiable factors in the control of heart disease, the Tucson AOD lung study identified factors leading to early detection, prevention and treatment of lung disease. Data are still being collected, continuing to give a clearer picture of how and why these diseases develop. Findings include the characterization of the impact of smoking on lung function, a description of how the prevalence and patterns of chronic airways diseases change with age and gender and the development of standards for lung-function tests. Lung-function abnormalities in adults have been demonstrated to have roots in abnormal lung function detected physiologically in childhood. Other findings changed lives. For example, asthmatics now know about factors related to asthma that they didn't know before. Early findings suggested ways to manage lung disease. People learned that they could avoid exacerbating the disease by eliminating certain environmental factors. They learned that they could replace household carpeting and reduce their exposure to house-dust mites, proven to be one of the most potent of allergens. They discovered that if they would limit their exposure to outdoor pollens and molds, they could reduce the severity of their disease. Physicians began to teach their patients what they could do on a routine basis to self manage their







Michael Lebowitz, chair of the Epidemiology graduate program.







disease. The study also revealed that asthma at all ages may have characteristics that suggest an allergic basis. The Tucson SCOR study, with findings of other SCOR grants throughout the country, contributed greatly to a better knowledge of asthma. A national educational program was launched. Smoking, environmental dusts, pollen, air pollution, and allergens were shown to have an affect on lungs and airways. Today, it is common for radio and TV weather forecasters to announce pollen counts and air quality readings and warn about the safety of venturing outdoors on windy days.







Through the years, researchers at the Respiratory Sciences Center won successive bids and grants were renewed every five years since 1971. The SCOR grant is the largest single grant ever awarded to a UA research team and the longest running study at the University. Research results led to other grant proposals and other awards. Three population studies, a physiology study, four basic sciences projects, and a Children's Respiratory Study were all spun off from the original grant. Frequently commended for an invaluable contribution to understanding lung disease, the Respiratory Sciences Center is considered one of the best centers in the world, Burrows says. Recalling those early days, Burrows reminisces fondly: "Every time I pulled data off the computer that I'd never seen before I'd run down the hall shouting to all `look what I've learned -- just look at this.' That's how I get my kicks," he said. "I now know something nobody else has ever known." by Nancy Guthrie







Preventive measures help keep us breathing easy.







Community Responds with Enthusiasm to Study



When news of the $5 million SCOR grant award reached Tucson back in 1971, euphoria soon turned to reality as the team considered the immense project. Dr. Ben Burrows immediately set about organizing the group. Co-investigators Professor Mike Lebowitz, the epidemiologist, and Pulmonary Physiologist Dr. Ron Knudson, set to work. Lebowitz refined and formulated standards for the questionnaire while Burrows and Knudson worked on lung function tests. They hired a nurse interviewer-- Bobbe Boyer--to enroll study participants. Expert salesmanship and a lot of legwork would be required to successfully convince nearly 4,000 people to participate in a lungdisease study expected to last five years. Boyer's instructions were simple. Once the boundaries were defined, she was instructed to "start on a certain corner, second house in, and knock on doors at every sixth house," Lebowitz explained. She invited whoever was home at the time to participate. "We don't know if it was community pride in the new medical school, people's interest in lung disease, or Bobbe's powers of persuasion that convinced people to enroll," says Burrows. "Whatever the reason, participation was excellent and their enthusiasm contagious." All ages and all socio-economic groups were represented. Participants filled out lengthy questionnaires and submitted to a variety of tests, including specially designed lung function tests, blood tests and skin tests for allergies. Through the years chest X-rays, blood pressure screenings and a variety of other tests were added. Results were sent directly to the participant or to their physician. As the years passed, only 14 percent of the original group of participants dropped out. These were unusually high rates of commitment according to an NIH review team. Today, the original group of 4,000 has grown to 5,700. Two hundred people are over the age of 75 and several are nearing 100. One study participant is 101 years old. "It's been fantastic to work in this community for the past 25 years," Burrows says. They've been tremendously helpful, and we're very grateful."







Investigators continue to follow many original participants in the lung disease study who have moved to other parts of the nation and world.







Tucson has always been open to the idea of medical research, he continued. It's a health conscious town and is considered a health spa. "People come here from all over the country for arthritis cures and asthma cures," he says. When University researchers need participants for clinical trials or other research activities, hundreds enlist. The 1971 lung study marked the beginning for the UA College of Medicine researchers. Other young investigators took notice of the Tucson community's enthusiastic participation and they soon began to envision other research, other diseases to conquer. "We made it much easier for the Cancer Center to get going," Burrows says, "Our study's success was an inducement for others to come." by Nancy Guthrie







Searching for Clues to What Causes Asthma



Think of him as a hunter. Or a solver of complex puzzles. Or a researcher on a mission. Fernando Martinez, M.D., associate professor of Pediatrics in Pulmonology at The University of Arizona, is determined to discover what causes asthma. Inside the nucleus of nearly every cell in the body, a complete set of genetic instructions, known as the human genome, is contained on 23 pairs of chromosomes. Chromosomes are mostly made of long chains of a chemical called DNA-deoxyribonucleic acid. "We know very well the consequences of asthma," Martinez says. "But we do not know what causes it." "We know that asthma runs in families--that it is a genetic disease," Martinez says. "And we know that asthma is increasing. But in spite of all the work done in this area, there are many things we still don't know." Is asthma increasing because of changes we've made in the environment Who is susceptible to developing asthma Exactly what genes cause asthma And what function do those genes perform If a person is predisposed to developing asthma, can the disease be forestalled Martinez is the principal investigator of research funded by the National Institutes of Health (NIH) to discover the genetic cause of asthma. He also is a faculty member of the UA Respiratory Sciences Center and the Steele Memorial Children's Research Center. Recently he received the prestigious NIH Research Development Award for Minority Faculty--a five-year grant. This award recognizes an already accomplished junior investigator and offers him or her the opportunity to devote more time to research. "For me, this grant represents five years of privilege." Martinez says. "Identifying and understanding the genes that cause asthma will pave the way for a cure. This is the essence of it all." Working in concert with the Children's Respiratory Study, Martinez has selected for study approximately 200 families with asthma. The Children's Respiratory Study has followed more than 1,200 children







for the past 15 years to learn about the development of respiratory illnesses such as asthma and allergy in childhood. Blood samples drawn from every member of these identified families allow Martinez to analyze their DNA and look for which specific pieces of DNA might be associated with asthma or risk factors for asthma. Even with an identified population, the process is not an easy one. Human DNA has been described as a biological computer program, some 3 billion bits long, that literally spells out the coding for making proteins, the basic building blocks of life. Somewhere along that strand of DNA lies the secret to what causes asthma. "Unfortunately, asthma is a very complex disease," Martinez says. "It is not caused by a single gene but by a variety of genes." That makes looking for the genetic culprit all the more difficult. The research Martinez has undertaken would not be possible without the progress that has been made by the Human Genome Project. The multibillion-dollar genome project has produced a "genetic map" linking many genes of interest to known chromosomal landmarks. This map gives researchers like Martinez guideposts, but the search for a specific gene is ever-complicated. It's like trying to pinpoint on a map the exact location of every city and town in the country, and all you know now is where the states are. "When we identify the genetic causes of asthma, we can either alter the consequences of a gene defect or alter the gene itself through gene therapy." Martinez cautions that gene therapy to cure asthma is a long way off. Martinez's work also has moved forward with an assist from Robert Erickson, M.D., the Holsclaw Family Endowed Professor in Pediatric Genetics at The University of Arizona. "Bob trained me in molecular genetics and literally opened his lab to me. It's been fantastic." Martinez and Erickson work in laboratories that were donated by Angel Charity for Children, Inc. The implications of Martinez's work will be dramatic. In the United States, 4 million children suffer from asthma. It is the number one reason children are hospitalized and the primary reason children miss school. And even with our best diagnoses and treatment, nearly 5,000 Americans die each year from asthma. "As a physician and a pulmonologist, asthma is a condition I see very often in young children. I kept wondering if lung disease early in life means lung disease later in life. Is the script already written Or can we do things to alter the progress of this disease" Chances are that five years will not be enough time to unravel the







complexities of the DNA and determine the causes of asthma. But Martinez says he can be patient. This research is his opportunity of a lifetime--the chance to discover something that can improve the lives of millions of people throughout the world. by Kate Maguire Jensen







UA Researchers Target Onset of Asthma



In the near future, individuals at risk for developing asthma may be able to avoid the disease entirely by taking a substance that manipulates the body's immune system, preventing onset of the disease. Although such therapy may sound futuristic, "I think we may only be a few years away from such a breakthrough," says Marilyn Halonen, associate director of the Respiratory Sciences Center and a professor of Pharmacology, Micro-biology & Immunology at The University of Arizona College of Medicine. Indeed, developing a means to prevent asthma is the focus of a major research effort at the Respiratory Sciences Center, the oldest of seven centers of excellence at the UA College of Medicine. Such a medical advance would save our nation billions of dollars--and an untold amount of suffering. In 1990, asthma accounted for an estimated $3.6 billion in direct medical expenditures and nearly 1 percent of all health-care costs. And the incidence of asthma appears to be on the rise, with Arizona having a particularly high prevalence of the disease. "We're not simply trying to alleviate symptoms for an underlying disease that will continue throughout peoples' lives," Halonen points out, "We're seeking to prevent the onset of asthma by manipulating the immune system of those children who are at very high risk for developing the disease. Our goal is to prevent asthma--and not cause something else during the process." Recent major advances in immunology and molecular biology have made such advances possible. In the past, experts believed asthma came in two varieties: extrinsic, in which an allergy triggered an attack, and intrinsic, in which no apparent external cause was determined. In February 1989, however, several Respiratory Sciences Center faculty members (including Halonen) authored an article published in the New England Journal of Medicine that challenged that long-held notion by suggesting that asthma "almost always" has an allergy basis. (Other authors were Benjamin Burrows, center director, and center members Fernando Martinez, Robert A. Barbee, and Martha Cline.) In response to allergens, the body produces high quantities of allergen-specific molecules known as immunoglobulin E (IgE) antibodies. The Respiratory Sciences Center researchers established







Marilyn Halonen, Associate Director, Respiratory Sciences Center.







that IgE has a very close association with asthma--in short, people with higher levels of IgE have a higher risk for developing asthma. "We found a very close association between the prevalence of asthma and the level of IgE antibodies. So although there still may be a small group of people who have asthma that might be non-allergic, we think the vast majority have an allergic basis to their asthma," says Halonen. This finding opened the door to potential preventive therapies, using the latest techniques from molecular biology and immunology. "If we can understand in great detail how IgE synthesis occurs, we should be able to interrupt it in a very specific way," Halonen says. "We believe this would pose no health threat to humans because many perfectly healthy people have very low levels of IgE." Through laboratory experiments, researchers have learned much about how IgE is regulated, "So we know some of the factors that by their concentration can lead to a facilitation or inhibition of IgE synthesis." These factors are called cytokines (proteins that direct the activities of other immune system cells). Cytokines are produced by T lymphocytes and monocytes (white blood cells that form part of the immune system). "So my laboratory is looking at the ability of lymphocytes to produce some of these factors. People who develop asthma may have an alteration in their ability to produce some of these substances. They may make too much of certain ones or they make too little of others."







UA researchers are studying five cytokines that have been shown to regulate IgE synthesis: interferon gamma, interleukin-4, interleukin-5, interleukin-13 and interleukin-12. "We've done the most work with interferon gamma, which when present in high amounts inhibits IgE synthesis. We know these substances are involved in the regulation of IgE in the test tube, but we don't know which are playing the most critical role in the body," she says. Allergic hypersensitive response where IgE antibodies on mast cells are cross linked by antigens (allergens). This initiates cellular As part of the effort to answer that question, Halonen's team is taking blood samples from a large group of children and then following them to determine if they develop allergies and/or asthma. (This effort is







events leading to the release of histamine and other pharmacological substances.







part of the Children's Respiratory Study, a project that is following more than 1,200 children from birth, studying the risk factors for the development of acute and chronic lung disease, especially asthma.) "We have found that the ability of 9-month-old children to produce interferon gamma was lowest among those who later were shown to be susceptible to allergic conditions. We tested them at age 6 for `skin test reactivity' and the kids who were most positive at age 6 already had shown the decreased ability to produce interferon gamma at 9 months." Halonen's research team also suggested the importance of early "sensitization" (the initial meeting of an allergen and the immune system) to certain substances associated with the development of asthma. "It may be critical to the majority of asthma (sufferers) that this exposure and the sensitization occur during the first year of life." The technical nature of this research may seem daunting, but the goal is easily understood: "We're trying to do something very specific that actually will prevent asthma from developing. My feeling is that we're going to understand this system well enough in the next few years that we will understand how to alter it." Specifically, UA researchers are exploring potential ways to slow or halt production of IgE in the body. "IgE synthesis occurs in B cells," Halonen says, "Early on, a B cell has `choices' about the kind of antibody it's going to make. We're not certain exactly how it makes those choices, but we do know that certain things must be present for it to make the choice for IgE. And one of them is interleukin-4, a protein made by T cells. "So the T helper cells' job is to help B cells make antibodies and become committed to making antibodies. The Th2 cells make interleukin-4, which looks like the crucial cytokine for IgE. If we could interrupt the T helper cells from making interleukin 4, it's highly likely that IgE would not be made," Halonen says. Being on the verge of this and many other potential medical breakthroughs makes this an extremely exciting time for research scientists, Halonen says. "We're beginning to understand these substances by their chemical structures, so the rules for how they act are beginning to be understood. For me, that is very magical, because there are incredible signaling networks, incredible hierarchies, and chemical reactions continually going on --and they're in some kind of amazing balance within an organism. To begin to understand how all of that is occurring, in an incredibly marvelous organized way, is absolutely amazing!" By George Humphrey







Searching for New Ways to Treat Asthma



As the number of people with asthma continues to rise throughout the country, researchers are looking for new ways to treat this chronic illness, including novel approaches such as gene therapy. In the past 10 years, the number of asthmatics in the population has increased almost 60 percent. In Tucson, one in 10 people has this illness, which is characterized by inflammation of the bronchial tubes in the lungs. Almost 15 percent of children in Tucson have asthma, which is the most common chronic illness of childhood. "It's a very common disease here," says Dr. John Bloom, associate professor in the Departments of Pharmacology and Medicine at The University of Arizona College of Medicine Respiratory Sciences Center. "Physicians throughout the country have been sending patients to Arizona for lung disease for 50 years or so. It seems the population now has a predisposition, at least genetically, because asthma appears to be inherited." As the children and grandchildren of people who moved to Arizona years ago to relieve asthma symptoms grow up, researchers like Bloom and his collaborator Roger Miesfeld, associate professor of biochemistry at the College of Medicine, have an entirely new population to treat. "More people are becoming asthmatic all the time," Bloom adds. In asthma the bronchial tubes constrict. This narrowing of the bronchial tubes causes the symptoms of asthma, like shortness of breath and wheezing. Bloom and Miesfeld are among a group of researchers in the United States who want to find a new way to treat the disease. Bronchial tubes in the lungs are affected on the cellular level. The way it most likely works, Bloom says, is that specific genes in the lungs get "turned on" and make proteins that cause inflammation in the bronchial tubes. Through research, Bloom and Miesfeld hope to find a way to "turn off" these same genes decreasing the inflammation in the bronchial tubes and eliminating symptoms of asthma. It is well known among physicians that the most effective treatment for asthma is corticosteroids, such as cortisone or prednisone. The effects of cortisone are produced through proteins called glucocorticoid receptors that are found in all cells in the body.







Roger Miesfeld, associate professor of biochemistry, and John Bloom, associate professor in the Departments of Pharmacology and Medicine.







Activation of glucocorticoid receptors in the lung by cortisone produces the effects that eliminate the asthma symptoms by "turning off" certain genes in the lungs. Inhaled, ingested or injected, cortisone is effective, but these medications have serious side effects, especially in children. Getting cortisone by mouth allows the medication to go throughout the body and affect organs besides the lungs. It also suppresses the adrenal glands, where cortisone is made naturally. Taking cortisone as a pill works, but may cause bones to thin and cataracts to form in the eyes. This can happen to people of any age after taking cortisone orally for months or years. Inhaling cortisone as a spray may not be as effective as taking it orally, but causes fewer side effects. Unfortunately, cortisone, even when inhaled, may activate glucocorticoid receptors in other organs leading to harmful side effects, such as slowing growth in children. If researchers can find a way to bypass the use of cortisone, they can effectively treat asthma without any of the negative side effects caused by cortisone. This is the type of research Bloom and Miesfeld have worked on for the past two years. They are looking at a genetically engineered glucocorticoid receptor that is "turned on" without cortisone. The gene for this activated glucocorticoid receptor could be inhaled directly into the lung. Because no cortisone is introduced into the body, this therapy would have none of cortisone's negative side effects. "Patients would inhale the gene for the activated glucocorticoid receptor and it would enter the lining cells of the lung and make the activated receptor protein," Bloom says. "This type of therapy would decrease inflammation in the lung without taking cortisone." Current studies are taking place in test tubes and in a rabbit model of asthma. The use of this new biological technology is at least 10 years away from a clinical trial, Bloom says. At this time, researchers are still trying to find out if this therapy could negatively affect the body if it gets outside the lungs to other organs. No one knows what this may do to other organs, but it's an important question that Bloom and Miesfeld must answer. Bloom and Miesfeld continue to work on perfecting this new medication that eventually could help a large segment of the country's population. "Some people wake up every night of their life short of breath," Bloom says. "Asthma can be a horrible disease." by Jordan Gruener







Keeping Exposure to a Minimum Helps Asthma, Allergies



Mary Kay O'Rourke thought she was just being a `wimp.' She would wheeze and, sneeze, her nose would run and her eyes would itch when she hiked outdoors or worked in fields of Burmuda grass. She insisted on trying to fight it-- she hiked during peak allergy seasons and continued her geology work in fields of pollen-coated weeds. "It was sheer stubbornness," O'Rourke said, "I'd go out and pull weeds and when I started wheezing, I kept thinking I was a wimp. Unfortunately, I just kept putting myself in the position of being exposed repeatedly to pollen and allergens." Mary Kay O'Rourke works at allergy free living. Her cat receives a weekly sponge bath. That continuous exposure transformed O'Rourke from a person with mild allergy symptoms to one with hypersensitivity. Exposure to pollen and allergens now cause her to have severe asthma and allergy symptoms. These changes have dramatically affected her life. She can no longer have carpet in her home, a cleaning woman has to clean her wood floors twice, once with a dry mop, the second with a wet mop, and she stays inside on high-pollen days. She also washes her cat once a week, stating that she remained too stubborn to actually give her cat away. While going through these incredible changes in her life, O'Rourke also was working as a graduate student with her mentor, Michael Lebowitz, Ph.D., associate director of the Arizona Respiratory Sciences Center, one of seven "Centers of Excellence" at The University of Arizona. Both researchers are nationally recognized for their work in respiratory sciences. With a doctorate in geosciences, O'Rourke readily admits that she is the only geologist (and palynologist) working at The Arizona Health Sciences Center. However, her knowledge of household allergens is unrivaled. She and Lebowitz have measured indoor and outdoor allergens and their effect on inducing asthma and allergies in Tucson, which has double the national rate of airways obstructive diseases, especially asthma, chronic bronchitis and emphysema. Lebowitz began working with household allergens and asthma nearly 20 years ago. As a young scientist at The University of Arizona, Lebowitz was funded by the Specialized Center for Research (SCOR)







grant from the National Heart, Lung and Blood Institute. The Arizona Respiratory Sciences Center is the only center nationally that has been funded continually through this program. As the project began in 1977, Lebowitz and his team searched for allergens and how they related to asthma. Because of their studies, funded by many agencies, they have learned much more about allergens, pollens and how the body's immune system reacts to them. Cited nationally and internationally, Lebowitz and O'Rourke have shown an exposure-response relationship with allergens. Just as O'Rourke experienced her asthma and allergy symptoms worsening, the more a person is exposed and sensitized to pollen , the worse their symptoms may become. "We can show that an exposure-response relationship exists. In asthmatics, there is a bronchial response and it is very much related to what they're sensitive to," Lebowitz said, "We've learned a heck of a lot about allergens and the immune system. The preliminary findings of our studies are very important and we continue to learn more each year about allergies and asthma." To study this response effectively, Lebowitz and his team of researchers have worked with a willing and representative Tucson population. What they learn in Tucson can be applied in many other areas of the world. "We're probably doing more in Arizona now than anyone else is doing in any other part of the country. One reason we have a Center is that it has allowed us to bring in people from all over the campus, the country and the world and collaborate." They work with a variety of other departments on campus, including medicine, pediatrics, psychiatry, biology, geosciences, engineering, Office of Arid Lands and entomology. O'Rourke was responsible for showing that house-dust mites could live in Tucson, where it was thought that the hot and dry weather would be their death. "House-dust mite does occur in Tucson. We didn't believe it did because of our hot and dry climate," O'Rourke said, "Evaporative coolers and carpets help house-dust mites survive. Carpets in the Southwest are particularly good. Although the air is dry, there's a micro habitat in the carpet that has higher humidity. This also exists in the chair you sit in and the bed you sleep in. They're all a highhumidity, warm environment." Yet even the way houses are built in Tucson contributes to the housedust mites, O'Rourke said. The concrete slab construction used here allows condensation to form when the cold cement contacts the warm house.







House-dust mites are small, microscopic arthropods, (related to spiders) in the tick group. They are one of the most potent allergens, Lebowitz said. "That is why this is one of our interest areas. We have the problem in Tucson, but around the world people are suffering from asthma and allergies related to the house-dust mite." Although the house-dust mite is thought by some to be the most potent, spring time in Tucson is overloaded with billions of pollen particles floating through the air from weeds, trees, plants and grass and mold. These allergens blow about in the air and when inhaled, the protein found in these pollens and allergens can cause an immunologic response in those with allergies. "If you look at a daily concentration of pollens and allergens, there are thousands outside, but only a small number come inside," O'Rourke says, "Some blow in, some are carried in our clothes and shoes and others come in on our pets. Most of these proteins are water soluble, so they can be washed away. But if they're in your carpet, they stay there." External events also affect people in Tucson. "In Tucson in the 1880s there were dirt floors. In the 1920s, evaporative coolers came in and humidity inside Tucson homes began to rise. Carpets came in postWorld War II. Carpet really is a sign of success. The thicker the pile, the greater sign of success," O'Rourke says, "Unfortunately, a greater incidence of allergies comes along with these changes." Lebowitz and O'Rourke also are studying environmental toxins that may create or worsen asthma and allergies. If a person is exposed to diesel exhaust and to pollen, they are much more likely to get asthma and allergy, he said. They found this occurrence in Japan, which has many pine trees and diesel trucks. "We've also looked at air pollution. There are many different kinds of gases, fumes and secondhand smoke that can have a similar effect on people," Lebowitz says. Some of their recent work in this area has been included in the most recent Environmental and Protection Agency (EPA) report on smoking and respiratory health. One of his latest projects is one of two in the country for assessing exposure to toxins that affect people, such as metals, pesticides, gases (organic compounds) and additives in gasoline. Although it sounds like there's nothing a person can do to keep pollens, allergens and toxins out of a home, it's just not true. Stemming from their work with National Institutes of Health and the World Health Organization, Lebowitz and O'Rourke recommend avoidance and removal of exposure sources. Some tips are simple, like mopping the floors, and others are more complicated, like removing carpeting from a home, keeping mattresses in plastic covers and not having a pet.







"People do not want their lifestyle affected," O'Rourke said, "Nevertheless, people don't realize they need to take care of themselves. What may be minor allergies today, could become hypersensitivity. They need to make sure their indoor environment is good and protect themselves from exposure." by Judy Elam







Healthy Children Help Researchers Study Illness



No one likes to think of babies as uncooperative. But imagine the results you'd get asking newborns to take a deep breath and then exhale slowly. That was one of the early challenges faced by a team of researchers at The University of Arizona Respiratory Sciences Center when they began what has now become a 15-year study of the risk factors children face for developing acute and chronic lung disease. Called the Children's Respiratory Study (CRS), it is one of the country's largest studies of respiratory health in childhood and possibly the only one of its kind in the world. In 1980, researchers with the CRS began following 1,200 healthy infants to examine the causes of both acute respiratory tract illnesses such as bronchitis and pneumonia and the development of chronic lung diseases such as asthma. Today, 950 of those children remain part of the study. The principal investigators in the study are Wayne Morgan, M.D., associate professor of Pediatrics and Physiology and chief of Pediatric Pulmonary, Anne Wright, Ph.D., research associate professor in Pediatrics and Fernando Martinez, M.D., associate professor in Pediatrics. Lynn Taussig, M.D., who was the former head of the UA Department of Pediatrics and director of the Steele Memorial Children's Research Center, played a major role in the early years of this study. In 1980 the researchers enrolled babies who were patients of a local health maintenance organization, Group Health Medical Associates (GHMA) in the respiratory study. These healthy infants have been tested at regular intervals for the past 15 years. In the early years of the study, CRS researchers and nurses obtained each child's medical records to identify illnesses for which the doctor had been consulted. At regular intervals, the parents of the children in the study answered questionnaires about the child's health. "Looking at such a large group of normal children gives us invaluable information about how respiratory diseases develop," says Morgan. "With a study of this magnitude, we are able to look not only at how many children develop respiratory illnesses each year, but what environmental, genetic and allergic factors influence the development of these illnesses." When the study began, researchers needed a better way to test the lung function of infants. The only procedure available was invasive --







inserting a balloon down the baby's esophagus to test the pressure in the lungs. This procedure was not all that accurate and parents of the children in the study might not have been willing to approve it for their babies. This led to the development of a simple, but innovative infant lung function test that is now in use in one form or another throughout the world. The new procedure involves loosely wrapping a plastic bag around a sleeping infant's chest. By quickly increasing the bag's air pressure for a few seconds, the chest is lightly compressed and the baby exhales as much air as possible. A mask over the infant's nose and mouth captures the air as it is breathed in and out, which gives an precise reading of the baby's lung function. "In the lab, we called this technique `the squeeze.' But in reality, the babies only experience as much pressure as they would with a strong cough," Morgan says. Other age groups of children presented other challenges. The test for six-year-olds required the kids to breathe at a certain pace for five minutes. To keep the kids focused on the task, Morgan developed a computer game where the kids' breaths kept a hot air balloon aloft. "This is scientific research," Morgan says. "But we had to be creative in the ways we obtained the data." One of the most unusual and principal investigators say, the most successful aspects of this study is the multi-disciplinary team that manages it. "Nearly every walk of science is represented," Morgan says. "To meet our goals we have an epidemiologist, anthropologist, pulmonologist, immunologist, physiologist and statistician on the team. Each of these professionals brings something unique to this study." As a for instance, few scientific studies have the benefit of a medical anthropologist as an ongoing member of a research team. Wright, a medical anthropologist, joined the UA faculty to help design the Children's Respiratory Study. One of her special areas of interest and expertise is how social factors affect disease. "In this particular study, we looked at things like smoking, breastfeeding and being in daycare to see how they affected a child's respiratory health," Wright says. "There's no way you can separate behavior from disease." Another area of special interest for Wright is ethnic diversity. She helped create the study to include Tucson's minority groups. "There are marked ethnic differences in illness behavior and patterns of health care utilization," Wright says. "When you exclude people, you







learn less." Wright's involvement has contributed immeasurably to the success of this research, Morgan says. "She helped design the research with an emphasis on people, not numbers. That's the reason we've developed such good rapport with the families in the study. We've kept track of all but 200 of the original families. That's a remarkable track record for a 15-year study," Morgan says. This research has been funded continually from its inception through a Specialized Center of Research (SCOR) grant from the National Heart, Lung and Blood Institute of the National Institutes of Health. In just the last five years, the SCOR grant has meant more than $14 million for The University of Arizona. The interest in studying lung function in children is growing. The work done at the UA Respiratory Sciences Center and other institutions strongly suggests that chronic lung disease in adult life may have its beginning during childhood. Illnesses which previously were thought to be unimportant may, in fact, produce subtle changes in the lungs of growing children that may lead to chronic symptoms later in life. The work done by the Children's Respiratory Study has made a significant impact on the body of knowledge about respiratory health. Here is a sample of some of the findings over the years. The Healthy Effects of Breast-feeding



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Longer duration of breast-feeding is associated with a lower incidence of wheezing lower respiratory illnesses in the first four months of life.







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Infants exclusively breast-fed for four months or more had half the number of episodes of acute otitis media (middle ear infection) in the first year of life as those not breast-fed at all. Repeated episodes of ear infections were also less likely to occur in infants who had been exclusively breast-fed for a longer time.







How Adult Smoking Impacts Children



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Lower respiratory illnesses were significantly more common in children whose mothers smoked, particularly if the mother smoked more than one pack a day and if the child stayed at home with the mother. Babies born to non-smoking mothers, but smoking fathers weighed an average of  pound less than babies not exposed to cigarette smoke during development. This suggests that mothers' passive exposure to cigarette smoke during







pregnancy may affect the growth of the fetus. Lung Function in Children







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Early infant lung function is an important influence on lung function in later life. Children who wheeze as the result of smaller airways generally do not have an increased risk of asthma or allergies later in life. Children whose wheezing is associated with allergies are more likely to be predisposed to developing asthma. Low lung function is a major predictor of wheezing in infancy.







What's Causing All This Wheezing







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Infants born to younger mothers (less than 21 years) had an almost three-fold risk of developing a wheezing lower respiratory infection compared to infants born to mothers 30 years or older. Both biological differences between older and younger mothers and sociological factors associated with young motherhood might explain these findings. Up until three years of age, children in a child care setting with three or more unrelated children had twice the risk of developing wheezing lower respiratory illnesses. Infants in child-care settings with smoking care givers were three times more likely to have wheezing lower respiratory illness than infants cared for by non-smokers.







What Do Genes Have to Do With It







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One indicator of allergic tendency, called "IgE" is inherited and follows a co-dominant pattern. That is, if one parent has a high level and the other parent has a low level, the child will often have an intermediate level.







During the next few years the CRS researchers will study this group of children in pre-adolescence and adolescence. "This study has been called a national resource," Dr. Morgan says. "It has been a wonderful example of collaboration between scientists with varied backgrounds and cooperation with the community. We hope it will continue for another 15 years." by Kate Maguire Jensen







Sleep Apnea Sufferers May Risk Heart Disease



If you wake up feeling as though you hardly slept during the night, you're not alone. About 40 million Americans suffer from serious and disabling sleep disorders, according to the 1992 report of the National Commission on Sleep Disorders Research. Surveys show that sleep disturbances are the most common health problem in the United States, and the consequences include reduced productivity, increased incidence of accidents and higher morbidity. Sleep apnea, the inability to breathe properly during sleep, affects an estimated 10 million Americans. Several studies have suggested that sleep apnea patients may be at increased risk for the development of heart disease, hypertension and stroke. The Respiratory Sciences Center at The University of Arizona College of Medicine recently received a $2.2 million grant from the National Heart, Lung and Blood Institute (NHLBI) for a five-year project to determine whether sleep apnea is a risk factor for the development of cardiovascular disease. The Center is one of six institutions chosen to be clinical sites to study the long-term cardiovascular consequences of sleep apnea. The other research institutions include Johns Hopkins University, the University of Minnesota, Boston University, New York University Medical Center and the University of California at Davis. Dr. Stuart F. Quan, professor of medicine and anesthesiology and director of the UA's Sleep Disorder Center, is the UA study's principal investigator; co-principal investigators are biostatistician and epidemiologist Dr. Michael Lebowitz, professor of medicine, and Dr. Paul Enright, research assistant professor of medicine. Researchers will study 6,000 patients across the country and follow them for several years to determine whether those with sleep apnea have a greater incidence of cardiovascular disease than those who do not. The Respiratory Sciences Center's study will include about 900 patients from the Tucson Epidemiologic Study of Obstructive Lung Disease (TESOAD) and the Tucson Health and Environment Cohort, and approximately 600 Native Americans participating in the Strong Heart Study in Phoenix, North and South Dakota and Oklahoma. (TESOAD is an ongoing prospective longitudinal study of the natural history of obstructive airway disease, funded by a NHLBI Specialized Center of Research grant under the auspices of the Respiratory Sciences Center. A unique feature of TESOAD is the data, available from more than 4,000 participants enrolled in the study since its 1972







inception, containing questionnaire responses concerning symptoms of lung disease, sleep disturbances and general health problems.) "Using patients from these studies will give us a random sampling of the population," says Quan. "Previous studies that suggest a link between sleep apnea and cardiovascular disease were retrospective and not randomized--all of the participants had sleep apnea. This study will compare cardiovascular outcomes for those who have exhibited sleep apnea as well as for those who don't." Participants will be tested for sleep apnea at local sites or in their homes. "We expect that testing will reveal some participants with sleep apnea who may be unaware they have it," Quan notes. Participants will be contacted approximately twice a year for five years to see if they develop cardiovascular disease. Symptoms of sleep apnea include excessive and loud snoring, apneas (respiratory pauses) during sleep, excessive daytime sleepiness, concentration and memory problems, decreased performance at work, memory loss, morning headaches, loss of energy and irritability. These problems may appear suddenly or develop slowly over several years. Because these symptoms are so common and seemingly harmless, most people don't think that evaluation and treatment by a physician may sometimes be necessary. However, if left untreated sleep apnea potentially can be fatal. Excessive daytime sleepiness can contribute to motor vehicle accidents, and some studies have suggested that severe sleep apnea can even induce high blood pressure, heart failure, heart attack and stroke. Of the two types of sleep apnea syndromes, obstructive sleep apnea is the most common and most severe. It is a chronic condition characterized by excessive and loud snoring, apneas (respiratory pauses) of 10 seconds or more while sleeping--sometimes more than 100 times in a night-- and excessive daytime sleepiness. In obstructive sleep apnea, the extremely loud snoring and labored breathing during sleep are caused by a blockage of the airway. If a complete blockage occurs, breathing stops. Pressure to breathe opens the blockage and the sleeper gasps and wakes so briefly that the episodes are not remembered as restless sleep. Obstructive apnea occurs more frequently in middle-aged, overweight males. The other sleep apnea syndrome, central sleep apnea, results from the brain failing to send a signal to breathe during sleep. The airway may stay open but the diaphragm and chest muscles stop working. The resulting decrease in oxygen levels in the blood sound an alarm in the brain, causing the sleeper to awaken and start breathing. People with central sleep apnea may be more aware of awakening frequently during the night than those who have obstructive sleep apnea. While sleep apneas occur in all ages, they become increasingly







common with age. One recent study indicates that 4 percent of middleaged men and 2 percent of middle-aged women are afflicted with sleep apnea. The prevalence may be higher among the elderly. "The Respiratory Sciences Center study will focus primarily on adults over age 40, since they would be most likely to develop cardiovascular disease during the study period," says Quan. "Our hope is that funding for this study will be renewed after five years, so that we can more accurately determine whether sleep apnea is a risk factor for the development of cardiovascular disease, which can take many years to develop." By Jean Spinelli







Universe is `Awash With Dim Galaxies'



The results of a major new survey for dim galaxies show that astronomers have been seriously underestimating the total number of galaxies in space. The new work shows that there are at least 30 percent and perhaps as many as 100 percent more galaxies in a volume of space than previously thought. The newly discovered galaxies had been overlooked because they are so faint, yet they may be the key to solving more than one cosmological mystery, including the apparent shortage of material in the universe compared with prediction of the `big bang' theory. The typical galaxy in the universe is a dwarf galaxy, ten times smaller and hundreds of times dimmer than the Milky Way, says Christopher Impey of the University of Arizona Steward Observatory, and member of an international team of astronomers who have been conducting a survey that concentrates exclusively on low surface brightness galaxies. "Previously overlooked galaxies may contribute as much material as the sum of all galaxies in existing catalogs," Impey says. "The universe is awash with dim galaxies." Results of the new survey are reported in a set of three papers to be submitted to the Astrophysical Journal. Impey collaborated in the research with his former graduate student David Sprayberry, now at Kapteyn Laboratorium in Groningen, the Netherlands, Michael Irwin at the Royal Greenwich Observatory and Gregory Bothun at the University of Oregon. The astronomers scanned plates taken with the UK Schmidt Telescope at Siding Spring, Australia, with the automated plate measuring machine in Cambridge. They then followed up with spectroscopy and imaging at the Multiple Mirror Telescope on Mount Hopkins, Ariz., the Steward Observatory 2.2meter telescope on Kitt Peak, Ariz., and the 305-meter radio dish at Arecibo, Puerto Rico. They found more than 600 previously uncataloged galaxies in a strip of sky centered on the equator. The new galaxies are at typical distances of 200 million to 400 million light years from the Earth, Impey said. "Our working assumption has been that we are ignorant of the true population of galaxies," Impey said, "It is very easy to hide large numbers of galaxies under the veil of the brightness of the night sky. Astronomers count the galaxies that are most easy to see. It's as simple as that." The low surface brightness galaxies may provide at least part of the answer to the so-called "missing mass" problem. The big bang theory predicts the existence of two to three times as much matter as is







UA Astronomer Chirs Impey and a team of astronomers from other universities have discovered new galaxies in space, solving the mystery of why there seems to be a shortage of material in the universe compared with "Big Bang" predictions.







observed in the sum of all galaxies in existing catalogues. Recent surveys indicate that black holes or brown dwarfs are unlikely to contribute a significant amount of mass. However, much of the shortfall can be made up of copious numbers of dim galaxies, Impey said. The team estimates that there are between 30 percent and 100 percent more galaxies in a volume of space than astronomers previously thought, but the amount of unseen mass they represent could be even larger as these low surface brightness galaxies appear to have substantial amounts of dark matter associated with them. The dim galaxies may explain such other cosmological puzzles as why astronomers see a phenomenal number of faint blue galaxies at between five billion and eight billion light years away when conducting sensitive deep sky surveys, but no counterparts in the nearby universe--until now. It turns out that the deep surveys have been better at detecting low surface brightness galaxies than have previous surveys of the nearer universe. "We believe we have identified local counterparts to many of the faint blue galaxies. Many galaxies were fiercely forming stars five billion to eight billion years ago, but have since faded to near invisibility," Impey said. Theories of large scale structure formation predict that many low surface brightness galaxies should have formed from small gravity fluctuations and should tend not to cluster in space. The new survey finds, as anticipated, that the dim galaxies cluster but not as tightly as do luminous galaxies. In 1987, Impey and Bothun, working with David Malin of the AngloAustralian Observatory, discovered the spiral galaxy Malin 1. This diffuse galaxy is still the largest and most massive spiral galaxy known, yet it was found serendipitously. Since then, Michael Irwin has been involved in the discovery of two dwarf satellites of the Milky Way, galaxies which are in our back yard, cosmologically speaking. These galaxies span a range of 40,000 in luminosity but they share the property of low surface brightness. by Lori Stiles







Independent Study Binds Teaching to Research



Physics Professor William S. Bickel conducts two ongoing research projects, and all the while involving undergraduate and graduate students in those and experiments of their own. The experiment that Bickel deems as his most important involves collisions between protons from the sun and high-altitude atmospheric gases. And what he calls his most interesting set of experiments centers on what occurs as smaller and smaller test tubes are used to analyze increasingly smaller biosamples. In the former, Bickel and his students derive information about atmospheric chemistry, excitation of atoms and molecules, charge exchange and destruction of molecules that make up the atmospheric shield that protects the earth from dangerous radiations from the sun. Very fast high energy protons from the sun never reach the earth because of the protective atmosphere, which slows and stops them. The protons collide with other molecules, breaking them apart and stealing electrons. "These very complex processes of colliding, stealing, ionizing, breaking and recombining reveal themselves by the emission of radiation that can be detected by instruments in satellites and on earth," says Bickel. Not all protons have the same speed, however, and not all pick up an electron during collision, leading to the conclusion that the instruments might miss some proton-molecule collisions. Lab experiments using a 2-million-volt Van de Graaff atomic accelerator do reveal answers. First, the protons are accelerated to a precisely known speed and then directed into a target chamber containing one of the atmospheric gases. Inside, the protons collide with nitrogen molecules and steal electrons, and the experimenters can determine, from the amount of light emitted from the collision region, how often and what percentage are involved in collisions. The latter line of experiments grew out of microbiologists' need to analyze the protoplasm from a single cell, an extremely small amount of biomaterial, 10 to the minus 12th power, or a millionth of a millionth of a liter. The material is placed in the test tube, which is an extremely small hollow glass fiber called a "capillary." A laser beam is then focused on the capillary, while a spectrometer-detector system is set up to collect the light emitted as a function of wavelength (color). A spectrum results, with peaks at various wavelengths that correspond to the relative and absolute abundances of the chemicals in the biomaterial. In this case, the experiments show that as capillaries get smaller, and approach the wavelength of the laser, distortions







Physics Professor William S. Bickel







occur in the spectrum. "Our work shows when this distortion starts to occur and how bad it can be. We found that when using very small capillaries, the inner diameters must all be precisely the same size for the data to be reproducible." Both projects are funded by the National Science Foundation. Bickel is dedicated to the idea that teaching and research go hand-inhand, and as a professor of physics, he constantly searches for ways to pull undergraduates and graduates as well into the exciting world of discovery. Bickel's definition of a university sheds even more light on his philosophy of teaching. "It (the University) is a collection of intellectual independent thinkers, and students whose main purpose is to join together to become educated. The faculty's duty is to educate and keep current in what they know. Therefore faculty are expected to both teach and learn. They learn through interaction--what their colleagues have done--and by doing research with students, they teach them how to learn from others, think for themselves and investigate new ideas. It is the way I work, and the way the University works, with students," Bickel says. Independent studies courses are his key to involving students in research projects. Basically this interaction (students involved in research) starts in the classroom or in his office. "They will come in with a problem, or a device; they have something interesting to talk about," he says. For example, a student brought in an old bottle and asked Bickel why it was discolored, why the fascinating patina had formed on its surface "I found that he was worthy of my time, so I gave him help and a place to work, " Bickel says. It is at this point in discussing undergraduate research projects with students that Bickel pulls out "the pink sheet" (it really is pink) containing all information that a student needs to know about independent studies in physics under Bickel's supervision. Bickel is serious about winnowing out students who might see independent studies as an easy way to get a grade, so the pink sheet explains, in no uncertain terms, the written work that must accompany lab work, required reading and, of course, testing. "They see the research is going to be a bit disciplined. It brings a formality, a dignity, a sense of obligation--me to the student, and the student to me. The student gets credit, the University gets credit and I get credit." Bickel says that in the past, many professors did not pay much attention to independent study, "but I formalized it." He sees independent study as a way to involve undergraduates and graduates as well in projects that have captured their interest and that lead to learning underlying principles of physics.







"I've always had between four and 10 independent studies students," Bickel says. One such student, Teresa Embry, is an undergraduate honors student who transferred to the UA after two years at Pima Community College. In a laboratory session dealing with electronic propulsion, Embry became interested in repairing a vacuum chamber that had sat idle in the lab. She wanted to use the instrument to test electronic thrusters and plasma generators. She and Bickel used her independent studies not only to ready the vacuum chamber, but as a way for her to learn the underlying principles of physics as well. To repair the chamber, Bickel taught Embry machine skills and let her use his personal lathe. She installed new seals, applied epoxy, cleaned and rethreaded the chamber. Besides practical skills and physics principles, Bickel also teaches skills that will aid a researcher throughout her career, Embry says. He teaches students to use the library, and how to write a proposal for funding. "Your physics classes won't teach you about development and funding," she says, " (and) they are vitally important." Armed with the skills she learns from her independent studies, she plans to work in the area of gravitational wave theory. "I want to go into research, but I certainly don't want to wind up in a lab and not know what to do." Embry speaks highly of her mentor. "He is always there, and he is always willing to help. He is not an intrusive teacher, "she says. "I think Dr. Bickel doesn't inject himself, but if you ask, he is willing to help. He doesn't say `do it this way or that way' but he will recommend, and say, `if you have another idea, we'll look at it.' He puts a lot of emphasis on working problems out," Embry says. She says Bickel uses every opportunity to develop critical thinking skills in students "even if the solution you thought of was wrong." "The (independent studies) lab wasn't required for physics majors, but it will help me become a better physicist. I will be a marketable physicist when I'm through," Embry adds. Another student, Danielle Manuszak, is beginning her third year at the UA. Last year, she participated in Bickel's independent study program using an undergraduate research grant awarded by the Honors Center. Starting from questions about how and why dew droplets form on spider webs, she has progressed to attempting to discover the relationship between the web strand thickness and the spacing between the beads of dew. Although she did not discover the exact relationship between the dew







drops and the web strands, Manuszak credits Bickel with opening the world of physics research to her. "You can do everything hands-on. He allows you to experiment for yourself," she says. It is not just Bickel's knowledge of physics that inspires his students. He creates an atmosphere in his laboratories that students find exhilarating. "Just finding my way around the lab, I learned a lot," Manuszak says. She says that Bickel often drops in to one of his labs and goes right to work alongside students. by Dennis St. Germaine







PREVIEWS & POSTSCRIPTS







ADAPTIVE OPTICS FOR PLANET SEARCHES With new giant telescopes to push adaptive optics as never before, ground-based astronomers should be able to realize a long-held dream --detecting planets circling nearby sun-like stars. A team of scientists, headed by UA astronomer J. Roger P. Angel, hopes to settle the question of whether Jupiter-like planets orbit nearby stars by surveying 30 stars within 30 light years by the end of the decade. Adaptive optics is a technique for correcting atmospheric blurring effects. It instantly analyzes the changing atmospheric wavefront above the telescope and simultaneously adjusts or warps optic surfaces to correct for that distortion before light is brought to a focus in the telescope. Angel and UA adjunct astronomy professor David G. Sandler of ThermoTrex produced an original and extensive analysis of how new-generation, ground-based telescopes can achieve the highest performance limits of adaptive optics and can be used in the search for extrasolar planets. Together with Michael Lloyd-Hart and Donald W. McCarthy of the Steward Observatory, Angel and Sandler have developed adaptive optics for the UA/Smithsonian Institution 4.5-meter Multiple Mirror Telescope (MMT) on Mount Hopkins, Ariz. Neville J. (Nick) Woolf of Steward Observatory and Jonathan I. Lunine of the UA Lunar and Planetary Lab are collaborating researchers. The ground-based, planet-detection system was conceived by scientists at The University of Arizona Center for Astronomical Adaptive Optics (CAAO), ThermoTrex Corp. in San Diego, the Air Force Starfire Optical Range in Albuquerque, and the UA Lunar and Planetary Laboratory. Angel is principal investigator at the CAAO, which was funded by the Air Force Office of Scientific Research last April. Contact Lloyd-Hart at 621-8353, McCarthy at 621-4079, Angel at 621-6541, Sandler at 6212288, Woolf at 621-3234, and Lunine at 621-2789. CLEANING TCE, PCB FROM WATER, SOILS A UA chemistry professor and his students and collaborators at Oak Ridge National Laboratories have invented an inexpensive and simple process that completely decomposes trichloroethylene (TCE), polychlorinated biphenyls (PCBs) and other chlorinated organic chemicals found in ground water, waste water and soils, and turns them into harmless compounds and gases. Quintus Fernando and UA chemistry graduate student Rosy Muftikian began work on the project two years ago with modest funding from Oak Ridge National Laboratories (ORNL). Fernando's graduate student, Carina Grittini, has been testing the process's efficacy in removing PCBs.







Conventional, but costly and inefficient, remediation systems pump water above ground to remove organics by air stripping or adsorption onto activated carbon. Canadian studies first suggested that elemental iron, though slow to work, could play an important role in removing TCE and other chlorinated organics from contaminated groundwater. Then one day, as "just a shot in the dark," Fernando and Muftikian coated the surface of the iron with a minute amount of another metal, palladium. Chlorinated organics were quickly and completely dechlorinated when passed through a column containing palladized iron and water at room temperature. UA chemist Mark E. Malcomson used gas chromatography and mass spectroscopy to verify that the TCE and other chlorinated organics were quickly dechlorinated by the process. Research Corp. Technologies, a Tucson-based independent technology management corporation, filed for patent protection last December and is commercializing the system on behalf of the UA and the inventors, Fernando, Korte and Muftikian. TCE and other chlorinated organics foul groundwater in at least half of the Environmental Protection Agency's 1,400 Superfund sites. The National Research Council estimates there are as many as 400,000 polluted sites around the country. Muftikian also found the system effectively rids water of chlorofluorocarbons. In addition to Muftikian and Grittini, graduate student Gino Romeo and undergraduate student Gerald Peiser are also involved in the research. Contact: Quintus Fernando, Rosy Muftikian, Carina Grittini, at (520) 621-2105 or e-mail: fernando@ccit.arizona.edu NEW GRADUATE DEAN This September, Thomas J. Hixon, the former head of speech and hearing sciences at the UA, will become the new dean of the Graduate College and assistant vice president for research. Hixon, 55, joined the UA faculty in 1976, became head of speech and hearing sciences in 1985 and director of the National Center for Neurogenic Communication Disorders in 1991. Hixon was chosen from four finalists after a six-month search. Hixon also runs the American Indian Training Program in the department. The training program has 1015 American-Indian master's degree candidates enrolled each year, and boasts a graduation rate of more than 80 percent. TOP QUARK University of Arizona physicists are part of the "D-Zero" experiment at Fermi National Acceleratory Laboratory which announced in March the discovery of the "top quark" -- the one particle physicists have searched for to confirm the current fundamental theory that describes the structure of the universe. Spokesmen for nearly 400 scientists with the D-Zero group and for another high energy physics experiment called the Collider Detector at Fermilab (CDF) reported the details of their landmark discovery at a scientific symposium in Batavia, Ill. Both groups began using Fermilab's upgraded Tevatron accelerator to search for the top quark in 1991. The CDF







group announced last April that it had probably found the top quark, and that its mass is about 174 billion electron-volts -- a mass heavier than an entire atom of gold. However, the statistics on top quark production in the CDF published evidence were too limited to determine whether the signal was real or merely a fluctuation of the background, some experts say. Since then, both D-Zero and CDF experiments have collected about three times as much data at the Fermilab Tevatron, say UA physicists Michael A. Shupe and Kenneth A. Johns. Presumably this is the last and heaviest quark which will be found, they add. UA physicists have been active collaborators on the D-Zero experiment since 1988. John P. Rutherfoord, head of the UA Experimental Elementary Particle Physics group, and Geoffrey E. Forden are the other faculty members working on D-Zero. Several post-doctoral researchers, graduate students and undergraduates also are on the UA team. The UA research is not focused on top quark counting, but rather has directly supported the construction, datataking and other related analyses of the experiment. Contact Shupe at 621-2356 or Johns at 621-6791. DESERT SCIENTISTS ON ICE Scientists want the baseline measurements to understand glacial changes that may be due to global climate change. Roger C. Bales, the principal investigator leading a field team of U.S. university researchers who are part of a NASA-funded project to map and measure the Greenland ice sheet, is going to collect shallow ice cores on the western margin of the ice sheet at 2,200 meters above sea level to measure annual snow accumulation rates. Bales, of the UA department of hydrology and water resources and the UA Institute for the Study of Planet Earth, and his team, are taking part in a National Science Foundation-funded study to collect data on the levels of hydrogen peroxide in the atmosphere and near-surface glacial snow -- data which relates to current levels of OH radicals in the atmosphere. OH, which has a lifetime of less than a second in the atmosphere, cleanses the troposphere of almost all pollutants, except for the ozone-thinning chlorofluorocarbons (or CFCs). Bales' group ultimately wants to study OH levels through the entire history locked in the 3,000meter-deep Greenland ice sheet. NASA wanted Bales' group involved in its ice-mapping and measuring program because the agency is interested in using hydrogen peroxide for dating annual layers in ice cores, McConnell said. Joe McConnell, a UA graduate student in hydrology, will analyze samples in "cold ovens" in the UA hydrology department before returning to Greenland in less than two weeks. When last there, he said, temperatures hovered at minus 31 degrees Fahrenheit, a bit cold when you sleep, as he did, in a tent. Contact Bales at 621-7113 and McConnell at 621-9486. SMART TRAFFIC SIGNALS The traffic light a mile up the road is green, and it stays green until you're within a few yards of the intersection, when it turns red. And it stays red. It stays red for three or four tunes, a







couple of spot breaks and a time and weather check on the radio and until you've forgotten why it was you got into your car in the first place. If this sounds horribly familiar, take heart. A group in the UA systems and industrial engineering department is working with local government agencies to try and smooth out some of the sometimes annoying idiosyncrasies of Tucson's traffic lights. The group is going to monitor the "data rich" Campbell-Speedway intersection -- a snarl of cars, trucks, buses, bicycles and pedestrians -- using video detectors, VCRs, fiber optic links, computers and other equipment. They will collect data and develop computer simulations for testing a more flexible and sophisticated method of controlling traffic lights. Call Larry Head, assistant professor of SIE, 621-8204, or e-mail larry@sie.arizona.edu REMODELING THE MMT Southern Arizona telescopes routinely shut down for maintenance during summer monsoon months. This year, however, the Multiple Mirror Telescope Observatory (MMTO) on Mount Hopkins is undergoing a major transformation, part of an upgrade to one of the world's more powerful telescopes. Staff of the MMTO, which is jointly operated by the Smithsonian Institution and the UA, shrouded the 4.5-meter six-mirrored telescope last May. Then TIW, Inc., of Albuquerque began a $720,000 building conversion. Major building modifications include installing new front shutters that are six feet higher on top and six feet farther forward, adding two smaller rear shutters to ventilate the telescope chamber, and adding louvers to the building interior to shield the telescope from Tucson light pollution, according to MMTO director Frederic H. Chaffee Jr. High winds shut down building conversion operations for a couple of days, but rain hasn't done much to slow things down, Chaffee added. Remodeling will be complete by October. The upgraded MMT will feature a single 6.5-meter primary mirror that was cast in 1992 by the Steward Observatory Mirror Laboratory. The lab now is polishing the 10-ton borosilicate "honeycomb" structure mirror. It will be trucked up to the MMTO site in the Santa Rita Mountains late in 1996. The upgrade will effectively increase the MMT's light-collecting power by more than twoand-a-half times, and it will allow astronomers to view an area of the sky more than 400 times larger, thus permitting large-scale surveys of faint objects in deep space.







DIRECTORY OF RESEARCHERS







John Bloom, M.D. Associate Professor, Departments of Pharmacology and Medicine (520) 626-6380 jbloom@scoraz.resp-sci.arizona.edu Bobbe Boyer Research Nurse, Respiratory Sciences Center 626-7091 bobbe@scoraz.resp-sci.arizona.edu Benjamin Burrows, M.D. Professor, Arizona Health Sciences Center Respiratory Sciences Center 626-6387 bburrows@scoraz.resp-sci.arizona.edu Robert Erickson, M.D. Holsclaw Family Endowed Professor in Pediatric Genetics Professor of pediatrics 626-5175 Marilyn Halonen, Ph.D. Associate Director, Respiratory Sciences Center Professor of Pharmacology, Microbiology & Immunology 626-6537 mhalonen@scoraz.resp-sci.arizona.edu Christopher Impey Ph.D. Associate Professor, Astronomy Steward Observatory 621-5006 cimpey@as.arizona.edu Ron Knudson, M.D. Arizona Health Sciences Center Respiratory Sciences Center 626-6387 Michael Lebowitz, Ph.D. Professor, College of Medicine 626-6379







lebowitz@scoraz.resp-sci.arizona.edu Fernando Martinez, M.D. Associate Professor, College of Medicine Pediatrics Respiratory Sciences Center 626-7780 fernando@scoraz.arizona.edu Roger Miesfeld, Ph.D. Associate Professor, College of Medicine Leon Levy Cancer Center 626-2343 miesfield@azcc.arizona.edu Wayne Morgan, M.D. Associate Professor, College of Medicine Chief of Pediatric Pulmonary Pediatrics and Physiology 626-7780 wmorgan@resp-sci.arizona.edu Mary Kay O'Rourke Research Associate, College of Medicine Respiratory Sciences Center 626-6835 maryk@pomea.hrp.arizona.edu Stuart F. Quan, M.D. Professor, College of Medicine Respiratory Sciences Center 626-6115 squan@scoraz.resp-sci.arizona.edu Anne Wright, Ph.D. Research Associate, College of Medicine Respiratory Sciences Center 626-6686 awright@scoraz.resp-sci.arizona.edu