FALL 1997
Keeping Pace With Medical
& Molecular Genetics
'97 Grads - Where They Are Now
Doris Merritt MD - A Profile
Ft. Wayne's Summer Research Program
Inquiry is the life of the science of medicine and inquiring minds ask questions. In this country, the university community offers an unparalleled environment for inquiry. Our cover story provides a glimpse at some of the questions and answers that have led to and issued from the School's Department of Medical and Molecular Genetics.
Most recently, Joe Christian, MD, stepped down as department chair after 20 years of successful leadership and his successful studies with twins. He is followed by Merrill Benson, MD, a rheumatologist with his own successes identifying gene mutations that create the accumulation of amyloid protein deposits in patients with a type of Alzheimer disease and an abnormality in fibrinogen (the clotting factor) in patients with renal amyloidosis. Both have continued the legacy of A. Donald Merritt, MD, the department's first chair, whose partner-in-life Doris Merritt, MD, is also featured in this issue. She has created a legacy of determination and achievement which is also embodied in the nearly 300 students who graduated this spring.
I hope you'll take a moment to read our Match Day story on page 8. You may also view a complete listing of new graduates and their residency locations on our website (http://www.medicine.indiana.edu). Some of these young physicians may have already been in your area during their first two years of medicine or third-year clerkship if you live in one of the eight cities or towns that are home to the School's Statewide Medical Education Centers. You also may have mentored one of them in a summer program like the one in Fort Wayne featured in this issue. We hope you'll actively support your new colleagues; call them or invite them to dinner or to your home. They welcome your recognition.
James W. Edmondson, MD ('69)
Editor-in-Chief
About the Cover: Chromosome painting from the IU Cytogenetics Laboratory courtesy of Octavian Henegariu, MD, research associate. Please also see page 3.
FALL 1997
This issue of INDIANA UNIVERSITY MEDICINE highlights medical and molecular genetics, an area of growing interest to all of us. Fascinating as each new finding is, it also brings with it immense new challenges for us as teachers, clinicians and researchers.
Francis Collins, MD, PhD, director of the National Human Genome Research Institute, is a good friend of many faculty at this school. When he tells us that within two to three years, we will have physical maps to locate the genes involved in disease and normal human development and that we will know the sequence of all genes and be able to survey DNA databases and analyze genes, I know we must make some important changes now to prepare our students for their future roles and responsibilities.
First, they must become lifelong learners who retain a high level of competence despite rapid changes in science and medicine. Second, they must possess the moral and ethical mettle to make treatment decisions which sustain the credo and guide the values of our profession. And, finally, they must possess the knowledge, skills and attitudes necessary to succeed in a time when the practice of medicine will be increasingly influenced by outside politicaland economic forces.
The School is making excellent progress in developing a new curriculum that reflects and responds to these challenges. Nevertheless, we still face several hurdles. Our new curriculum will be interdisciplinary, and this will require some de-departmentalization in order for faculty to teach in an interdisciplinary fashion. The new curriculum will also be competency based, so faculty and course directors must plan and make any needed changes in approach and content to ensure that our students achieve the highest level of competence. We must also continue to develop new ways for our students to learn in outpatient settings where most future patients will receive care.
This is a tall order, but one we intend to fill. As our school competes with other top schools for the best students, researchers and teachers, we must be willing to redefine ourself in the context of this new and continually changing world of medicine.
Indiana University School of Medicine students are always ranked among the best.
Many exceed the norm on their national boards and are sought after by some of the top
residency programs in the country. We can ensure their ongoing success by understanding
their future needs and preparing them to excel...as the physicians we entrust with future
generations, the researchers who ask questions as yet unimagined, the teachers of all the
bright young students yet to come, and the leaders who will help shape the future through
medicine
Robert W. Holden, MD ('63)
Dean, Indiana University School of Medicine
Fifty years ago a department of genetics, medical or otherwise, didn't exist at IU. In fact, the field of medical genetics didn't exist anywhere. Hundreds of thousands of lives were devastated each year by genetic diseases such as Huntington, Alzheimer and bipolar diseases, alcoholism and Down Syndrome, most of which were not yet recognized as genetically based. Few remedies or resources were available for patients and their families. And their hardship was made even worse by a general lack of empathy toward conditions which society accepted as being the result of a "weak character."
Today, a different story is unfolding. While cures remain elusive for most genetically based disorders, investigators have begun gene therapy trials to correct disorders such as cystic fibrosis and some cancers. And advances made by geneticists in recent decades have greatly improved the quality of life for patients and families the world over. At IUSM, the faculty of the Department of Medical and Molecular Genetics continue to make major contributions to this fascinating revolution.
The principles of genetics were born from Mendel's experiments with peas about the time of the Civil War, but it wasn't until the turn of this century that these principles were first applied to medical problems by Archibald Garrod. It took another half century before it was proved that the DNA (deoxyribonucleic acid) of chromosomes was the carrier of genetic traits and provided the physical basis for Mendel's genetic principles. The helical structure of DNA, which is essential for both the replication of genes and their mode of action, was elucidated by Watson (a doctoral student at IU during the '40s) and Crick in the '50s.
While the basics of molecular genetics were being assembled, "classical" geneticists at IU such as the late distinguished zoology professors Tracy Sonneborn, PhD, and Hermann Muller, PhD, (a 1946 Nobel laureate) were urging their students to seek broader applications for the basic observations made in their laboratories. One of those students was Catherine Palmer, PhD, ('53) now professor emerita of medical and molecular genetics. She joined IUSM in 1955 as part-time instructor and in 1962 established the cytogenetics laboratory for analysis of human chromosomal disorders.
Soon after, A. Donald Merritt, MD, joined the faculty as professor of medicine. Dr. Merritt started the interdepartmental program in medical genetics at IUSM which, in 1966, evolved into the Department of Medical Genetics (now Medical and Molecular Genetics) under his chairmanship. He not only performed important work on a number of human genetic diseases but managed the country's third medical genetics department with great skill. Among others, Dr. Merritt recruited P. Michael Conneally, MD, already well known as a population geneticist, Joe Christian, MD, PhD, who like Conneally had made the transition from animal to human problems and who would succeed Dr. Merritt as chairman of the department, and D.E. Hodes, MD, PhD, a self-described eclectic with experience in DNA structure and cancer chemotherapy.
Over the next 20 years, this group and their colleagues described some 30 genetic disorders, and three members of the original team - Drs. Christian, Conneally and Hodes - continue to provide leadership for further advances in the department. Among many other achievements, the department had the first DNA bank in the country, and continues not only to bank DNA but also to provide DNA diagnosis for a number of diseases. For one of these - Pelizaeus-Merzbacher disease - IUSM did the first testing and still provides most of the testing for the world. Dr. Hodes and colleagues have localized a number of genes on the x-chromosome (responsible for x-linked ataxia- dementia and diabetes insipidus, and Christian disease). Dr. Conneally was part of the international team that first identified the marker for the Huntington disease (HD) gene in 1983, and the gene itself in 1993, making direct testing for HD possible. Today he heads the National Huntington Disease Research Roster housed at IUSM. Dr. Christian, now associate dean for basic sciences and regional centers, has amassed three decades of studies involving identical and fraternal twins. In particular, his work has revealed the importance of the prenatal environment on human development, especially on the central nervous system.
This work has created core knowledge and opened the way for further research and collaboration. For instance, Dr. Christian's twin studies have led to a collaboration between IUSM and the Indiana Department of Health to provide consultation services to physicians whose patients have been exposed to environmental hazards during pregnancy. On other fronts, his group has collaborated with many other laboratories to examine the role of genes in complex diseases thought to involve numerous genes.
Among their findings has been the recognition that genes play a role in alcoholism, previously thought to be the result of environmental factors and individual choice. An important outcome of this work is the Center for the Study of Alcoholism and Alcohol-Related Diseases, a multidisciplinary research collaboration among researchers in Indiana headed by T.K. Li, MD, associate dean of research at IUSM, and funded by the National Institutes of Health (NIH). Recently renewed NIH funding will continue support of the array of researchers in the center who study genetic, environmental, psychological and social factors involved in alcoholism and related diseases.
Jay Tischfield, PhD, professor of medical and molecular genetics and director of the Molecular Genetics Program oversees repositories designed to store cell and DNA samples from families affected by Alzheimer disease and alcoholism. "To diagnose illnesses such as Alzheimer disease and to someday, hopefully, diagnose alcoholism, we need to study the DNA of the patient's parents, siblings and children," says Dr. Tischfield. "Knowing this, we established centers to store the DNA of families to help us make these diagnoses."
In his own lab, Dr. Tischfield has developed transgenic mouse models to help researchers better understand the origin of human diseases. One such model is for hereditary kidney stone disease and kidney failure caused by an enzyme deficiency - the same enzyme deficiency (which creates the same problems) in some forms of human kidney disease. This work was supported by the National Institute of Diabetes, Digestive, and Kidney Diseases (part of NIH). Another mouse he created allows testing for environmental toxins that could cause delayed onset of genetically based cancers in exposed individuals or their progeny.
Due to initiatives such as these, diagnosis of genetic disorders has made rapid progress. It has become commonplace for physicians and geneticists to use genetic testing to examine a fetus' chromosomes and genes for congenital disorders such as Down syndrome (DS), sickle cell anemia, cystic fibrosis and Tay-Sachs disease. In cytogenetic laboratories at IUSM under the direction of Nyla A. Heerema, PhD, professor of medical and molecular genetics, studies reveal the condition of the chromosomes, enabling detection of abnormalities which could disturb normal function. In the case of Down syndrome (also called trisomy 21) a third chromosome 21 is present or, less frequently, there is a translocation of chromosome 21 (a piece of it attaches to another chromosome). If the cytogenetic studies disclose any of these anomalies, the physician has concrete information he or she can discuss with the parents.
Yet while most physicians now routinely offer a blood test and amniocentesis to detect Down syndrome, not all parents choose to use them. Dave and Chris Ollier are a case in point. The Olliers wanted children very badly. Still childless after seven years and fertility treatments, they gave up their hopes for a family. Soon after, Mrs. Ollier became pregnant with their son Evan, now 18 months old. He was diagnosed with Down syndrome soon after his birth.
"We chose not to do the amniocentesis or the prenatal blood test because we both said that no matter what, we would raise the child. It is not in our beliefs to abort," Mrs. Ollier says. Still, like all parents, the Olliers prayed for a healthy child. When Evan was born, his small ears and features, slanted eyes and a space between the big and second toe raised the suspicion of DS. A neonatologist was called in to confirm the diagnosis and, that night, the Olliers felt shock and disbelief as their pediatrician, Steven Cline (residency '93), told them that Evan almost surely had Down syndrome. (Further tests would reveal that Evan had inherited three chromosome 21s.)
They spent the next seven months guarding his health in preparation for surgery. Following an arduous corrective surgery, Evan went into cardiac arrest. He was successfully resuscitated, >and then, to allow his heart and lungs to rest, he was put on ECMO (extra corporeal membrane oxygenation - an extended use of the heart-lung bypass procedure) for four and a half days.
Now, six months later, Evan is recovering many of the developmental skills he lost during his recuperation. "We've been through the mill," Mrs. Ollier admits. "In fact, we were on so many roller coasters the first year of his life that we are just now really getting to enjoy our son."
Although the Olliers shunned genetic testing on account of their beliefs, they credit their surgeon's skill and advances in medicine with saving Evan's life. "If Dr. Brown (John W. Brown, MD, Harris B. Shumaker Professor of Surgery) had not been there, we would have lost him," Mr. Ollier states. "And 10 years ago they weren't even putting kids with DS on ECMO - but without that we would not have him."
For DS patients, advances in pediatric cardiac surgery and intensive care have grown apace with genetic testing, now making it possible to treat some of the complications of genetic diseases and improve quality of life for many patients. When an infant with a congenital defect is born without prenatal diagnosis, physicians and parents quickly seek options for treatment. In Indiana, they most likely would be referred to David Weaver, MD, professor of molecular and medical genetics and head of the IU Genetics Clinic. Dr. Weaver's ability to provide quality diagnoses and counseling is based on years of research as well as a wealth of new online databases, and the expertise of faculty and staff in both the cytogenetics and the molecular genetics laboratories.
Since 1989, the Molecular Genetics Laboratory, under the direction of Dr. Hodes, has provided diagnoses based on the responses of DNA fragments to probes tagged with radioactive isotopes. Disorders for which a gene has been identified - including Fragile X syndrome (a leading cause of mental retardation), Tay-Sachs disease and cystic fibrosis - can be directly diagnosed with this procedure. "Many questions need to be addressed to determine the medical complications that the baby likely faces, the characteristics of the baby's disorder and the risk of the same or similar problems in subsequent pregnancies," Dr. Weaver says.
For parents like Jeff and Donna Hall, whose daughter Elaina was born with Down syndrome, information about their child's disorder is a double-edged sword. "It still hurts to think about the future and what might happen," Mrs. Hall says, referring to how Elaina will be treated by other children, whether she will ever be able to live independently and, ultimately, who will care for her if her parents are unable to. On the other hand, knowing what to expect lets the Halls do everything they can to help their daughter reach her maximum potential. "Our fears for Elaina aren't any different than they would be with any child," Mr. Hall says. "We want her to be able to achieve as much as she is able to do."
Other Disorders Have Few Treatment Options
Working together, teams of geneticists, psychiatrists, psychologists,
neurologists and many others are making strides in treating both the mental
and physical symptoms of Down syndrome and in teaching coping skills for
patients and their families. However, for some inherited disorders such as
HD or early onset Alzheimer disease, there are still few or no treatment
options. In these cases, genetic testing simply offers the opportunity for
advance planning of family and financial matters, quality- and end-of-life
issues. And, again, many of these individuals choose not to know. "Because
there is no cure, we don't encourage anyone to take the test," says Dr.
Conneally. "The 30 percent who want to be tested must be carefully
counseled. Eight percent of patients who have demonstrated symptoms of HD
commit suicide."
The outlook is especially dismal for those affected by early onset HD (a condition identified by Dr. Conneally). HD is an autosomal dominant genetic disorder in which nerve cell clusters in the brain degenerate leading to rapid, jerky involuntary movements and dementia. Patients typically survive 15 to 30 years after the onset of symptoms. Passed on by fathers who themselves suffer from the more common form of HD, early onset HD strikes males and females under age 20. It can be devastating to a family because while a mother is watching her child die, she most likely is watching her husband die from the same disease.
Or consider the dilemma faced by another young couple, "Kristen" and "David." Kristen is six weeks pregnant. Her husband David is at 50 percent risk for HD. Kristen wants to have the fetus tested for the HD mutation to enable her to decide whether to continue her pregnancy. Although she feels strongly that she does not want their child to be at risk for HD, David does not wish to know whether he carries the HD mutation.
This example is one of 29 case studies presented by Kimberly Quaid, PhD, and Gail Vance, MD, in their book "Early Warning: Cases and Ethical Guidance for Presymptomatic Testing in Genetic Disease" to be published in early 1998 by Indiana University Press. Dr. Quaid, clinical associate professor of medical and molecular genetics and of psychiatry at IUSM and head of the School's predictive genetic testing program for HD, and Dr. Vance, assistant director of the IUSM cytogenetics laboratory and director of the Indiana Familial Cancer Program, are nationally known for their work in the ethics of genetic testing. They counsel individuals and families interested in presymptomatic genetic testing as well as those who already know they have a heritable disease. In "Early Warning," Drs. Quaid and Vance bring their experience to bear on the challenges society faces with the rapidly expanding knowledge of human genetics.
For even the most scientifically uninformed, the recent efforts in medical and molecular genetics are hard to miss. In what may prove to be among science's most ambitious undertakings, The Human Genome Project directed by Francis Collins, MD, PhD, director of the National Human Genome Research Institute (part of NIH), aims by the year 2005 to map the entire complement of human genes (some 100,000 in all), to create genetic maps to study how diseases are inherited in families, and to describe the order of the nucleotide bases in DNA. The project also supports efforts that focus on the ethical, legal and social implications (ELSI) of genome research. With their peers the world over, scientists at IUSM will continue to contribute to these fascinating developments.
"We must maintain our present base of good genetic research and expand our bench research in cancer as well as Alzheimer, Huntington and Parkinson diseases," says Merrill Benson, MD, who followed Dr. Christian as chair of the Department of Medical and Molecular Genetics last year. "As a department, our sights are set on expanding our research and treatment of diseases that affect the lives of individuals as they age." The department is currently applying for a grant to establish IUSM as a Center for the Genetics of Aging. This funding would allow IUSM researchers to pursue several projects. One would involve the collection of DNA from WWII-era twins for studies on aging. It also would allow additional research into the aging factors involved in the onset of HD and amyloid diseases, which affect nearly every organ of the body as well as the central nervous system. Much of this work will build on the twin studies done by Dr. Christian and the research of Dr. Benson who identified the genetic error that causes amyloid plaques to form in some Alzheimer disease patients and in patients with amyloid kidney disease. This funding would also allow IUSM to establish a registry for Parkinson disease and to continue its collaborative research to locate the genes that cause it.
"The future physician must be prepared to understand the genetic basis of health and the metabolic processes of aging," Dr. Benson concludes. "We are seeking to answer the questions we know - Is death preprogrammed? How does aging occur? How much is desirable?' - as well as the questions we don't yet know to ask." For the faculty and staff at IUSM, teamwork and collaboration will continue to provide the answers ... and the questions.
Members of the IUSM Class of '97 arrived in 74 cities across the US this summer to begin their first year of residency. The 260 graduates are scattered among urban metropolises and small towns from coast to coast. More than half will remain in Indiana - both in rural and urban areas. Together they represent every major area of medicine, and nearly 60 percent will enter primary care.
For Ann Wojtalik, MD, her year off from medical school confirmed her desire to become a pediatrician. During that time she worked with a pediatrician and felt a real calling to help kids. Now, two years later, Dr. Wojtalik is pursuing her goal as a pediatrics resident at Riley Hospital for Children in Indianapolis. At the same time, Dr. Wojtalik has gained extensive experience in motherhood. Cassia, age four, Luke, age two, and Sophia, five months, were born to Dr. Wojtalik and her husband Chris while she was in medical school.
Dr. Wojtalik says communication, her husband's flexibility and their extended family's support are the keys to successfully managing such a hectic lifestyle. "Whenever things get too stressful, Chris and I re-evaluate. But we've both always thought I was doing the right thing," she says. She points out that while it's hard to balance a family, it's also hard to get through medical school without a family support system. And, she adds, "When you like what you're doing, it's easy to learn."
Dr. Wojtalik, who recently took time off after Sophia was born, is now beginning her residency on a part-time schedule. She hopes she can be a mentor to other students and residents who are juggling personal responsibilities.
Another '97 graduate, Chantal Miller, MD, believes the support and nurturing by people in her hometown of Gary helped her reach her goal of becoming a doctor. It was Dr. Miller's interaction with physicians and health care professionals at St. Mary's Medical Center where she was a volunteer that helped her decide on a career in medicine. She believes that being a mentor and encouraging young people are important, since youth are the future of our communities. "All kids need that kind of support," says Dr. Miller. After completing her residency at Wayne State University/Detroit Medical Center, she looks forward to returning to Gary, where she will join the pediatric practice of Steve Simpson, MD ('74). She hopes to use her influence as a physician to serve the community and make a difference. "A good medical practice involves more than being a good physician," she says. "People need to be dedicated to their community."
Dr. Miller was a recipient of the Indiana Primary Care Scholarship, which paid for her medical education in return for her commitment to practice primary care in an underserved area of the state for at least four years. She also received a scholarship from the Methodist Hospital of Gary Foundation with the stipulation that she return to Gary to practice.
Helping others be their best was also a driving force behind 1997 graduate Dr. David Magnusen's choice of career. He became convinced in high school that medicine was the right career. Later, as a medical student, he heard Randall Braddom, MD, chairman of Physical Medicine & Rehabilitation at IUSM, define this specialty as dealing with the function of the person by helping them achieve their maximum potential. "I thought that's the way medicine should be," he says. It also parallels his personal philosophy of always achieving his maximum potential.
A native of Elkhart, IN, Dr. Magnusen is doing his residency in physical medicine and rehabilitation at The Ohio State University in Columbus. His severe hearing loss led him to consider a career in otolaryngology, but surgery presented a problem since it was hard for him to hear people through their surgical masks. He jokes that transparent surgical masks would solve the problem.
"I don't believe in the word can't," Dr. Magnusen says. "Maybe you don't do something as well, but to say can't, is a defeatist attitude." He describes any disability as something you learn to deal with and make adaptations for as necessary. When discussing the type of doctor he wants to be, Dr. Magnusen remembers his undergraduate biology professor at IU whom he idolized. "He always had time for his students, and that's the type of doctor I want to be. I always want to put my patients first, take time to answer their questions, and let them know they're important to me."
In the future Dr. Magnusen also hopes to work with children. A fourth-year medical school rotation in pediatric endocrinology allowed him to work at a summer camp for children with diabetes, which made a lasting impression. He would like to get involved with Special Olympics or other camps for kids with disabilities. With his positive attitude, Dr. Magnusen should have a great impact on children.
Click here for additional information IUSM Class of 97 - residency locations.
Learning the Ins and Outs of Research
Ten years ago, Michael Mirro, MD, ('74) approached Barth Ragatz, PhD, ('71), assistant dean and director of the Fort Wayne Center of Medical Education, about creating a summer research program for medical students. Dr. Mirro, a Fort Wayne cardiologist, wanted to offer students an opportunity to learn about clinical research through an interactive experience. IUSM's medical education center on the Indiana-Purdue Fort Wayne campus seemed a natural partner.
To date, the Student Research Fellowship Program, which is co-sponsored by the Midwest Alliance for Health Education, has attracted some 148 students from the Midwest and has become an invaluable learning tool for participants. This year marked the 10th anniversary of the program, which has expanded to include law, nursing and undergraduate students as well as research projects that encompass basic science, public health, medical ethics and health care policy. Each summer about 20 students are accepted into the nine-week program and paired with a preceptor. Preceptors serve as mentors who help develop and guide students' research projects.
Dr. Ragatz is especially pleased with the support and eager participation of the local community and IU faculty. Primary and specialty care physicians, nurses and attorneys from Fort Wayne and faculty from IUSM and the IU School of Law have volunteered as preceptors. "The program could not exist if it weren't for our preceptors," says Dr. Ragatz. "They seem to enjoy and gain from the experience as much as the students. The opportunity to mentor and share their research expertise is quite rewarding."
Dr. Mirro agrees and has served as a preceptor almost every year since the program began. He enjoys watching students' enthusiasm evolve as they accept the challenge of their project and engage in research.
"Many of our students have been so influenced by their research experience that they have pursued a career in the same area," says Dr. Mirro. The experience also has helped several medical students secure entry into residency programs. Students develop a poster, meeting abstract and typewritten manuscript on their research, which they present at the end of the summer. Twenty-eight of the projects have been presented at national meetings or published in peer-reviewed journals. The experience is invaluable.
Stefanie Flora, a third-year medical student, participated in the program for two summers. After doing clinical research projects in cardiology and endocrinology, Ms. Flora gained an appreciation for research and enjoyed the exposure to both areas of medicine. She said the value for her was learning how much work is involved in conducting research, how to write a scientific paper, and how a physician can conduct a scientific study through his or her practice. In the process she also observed and assisted her preceptor in the clinic, which was a great way to explore different specialties.
The expanded program has given both students and preceptors a broader view of health care and the opportunity to explore different health care issues.
"We've been able to do some valuable cross-disciplinary work by including nursing and law students and professionals in the program," Dr. Mirro says. "The medical ethics and health care policy issues that have been addressed are important to health care professionals. We definitely need to expose students to the many different facets of their chosen fields."
Exposure is the key to the Student Research Fellowship Program. And students who participate in the program are guaranteed a worthwhile experience.
Students Sample First Course From New Curriculum
This fall, students at IUSM will sample the first offering of the School's new, enhanced curriculum. Planning for a new curriculum was initiated in 1993 by Dean Emeritus Walter Daly, MD ('55). A committee headed by Steven Bodgewic, PhD, assistant dean for primary care education, spent two years assessing programs at the country's best medical schools, studying trends in health care delivery and the impact of discoveries in medical science on clinical medicine. Based on this work, the committee recommended an approach which would stress interdisciplinary education and be competency based.
In 1996, Dean Robert Holden, MD, established a new Curriculum Council under the leadership of Philip Breitfeld, MD, to implement these recommendations. The course beginning this semester, "Concepts of Health and Disease," teaches first-year students how to apply basic science concepts to clinical problems. A second new course, "Cell and Molecular Biology," is planned for 1998-99. It will integrate aspects of traditional basic science and modern biology. Still in the planning stage are changes to the clinical curriculum.
Nine core competencies will be integrated throughout the curriculum. The Academic Standards Committee and the Evaluation and Assessment Committee are developing tools to evaluate the effectiveness of teaching and the competence of students in each component of the new curriculum.
IUSM's Multipurpose Arthritis Center received a $3.2 million grant from the National Institutes of Health (NIH) in April, becoming the longest-funded center of its kind in the country. Center director Kenneth Brandt, MD, professor of medicine and head of rheumatology at IU Medical Center, reports that IU's is the only research center to specifically focus on osteoarthritis. Currently its researchers hold NIH grants totaling nearly $15.7 million.
Most recently the center became the lead institution in a clinical study of doxycycline (a form of tetracycline commonly prescribed for the treatment of acne) and its ability to prevent the progression of joint damage caused by osteoarthritis. The study is funded by an $8.3 million NIH grant. Dr. Brandt is principal investigator for the nationwide study, and IUSM is the coordinating center for the six-center project. John Bradley, MD, professor of medicine, is principal investigator for the clinical trial at IUSM.
The study is built on basic and animal research done at IUSM which indicates that doxycycline reduces the levels of several enzymes responsible for the softening and degeneration of cartilage in osteoarthritic joints.
Osteoarthritis, the most common form of arthritis, afflicts an estimated 15.8 million Americans. Seventy percent of all people over age 60 have evidence of osteoarthritis. About 30 percent of those individuals suffer joint pain and impaired function. Without some way to control the disease, Dr. Brandt says, those numbers will only rise as Baby Boomers age.
What's a pediatrician doing as dean of engineering and technology? If it's Dr. Doris Merritt, professor emerita of the IU School of Medicine, she's simply wearing another hat - one of many she has donned during nearly 40 years of service. Her achievements have garnered honors from IUSM, IU School of Nursing, Purdue University, the National Institutes of Health (NIH) and the State of Indiana.
But to hear her tell it, she was just in the right place at the right time. An only child, young Doris Honig had a taste for independence and an innate dislike for the accepted feminine role of the time. An avid reader, she spent her free time browsing her father's books at the family's New York City home and wandering the city's museums. Yet for young women during the '30s and '40s there were few opportunities for independence "with respectability."
Clearly, an education was essential to her goal so she attended Hunter College, doubling up on credits to graduate early (Phi Beta Kappa, cum laude) in 1944. A two-and-a-half-year hitch as a Naval officer followed. Then, as WWII wound down, she once more weighed her options. "The women who had joined up were teachers or in merchandising, with a few in broadcasting," she says. "But it was clear they were there because they weren't getting anywhere in their jobs. My roommate had been premed, and I urged her to finish. Finally she said, if this is such a great thing, why don't you do it?"
So, with only two science courses to her credit, she got the catalogue from George Washington University School of Medicine and called on the chairman of the admissions committee. "I said I would like to go to medical school," she recalls with a laugh. "He was very polite and asked if I had any idea how many people shared that desire. I knew it was difficult, I said, but what was bothering me was - did I really have to take all that science to get into medical school? Poor man. He said, yes, I really did."
Two years later, prerequisites complete, she was admitted as one of three women in a class of 80. She earned her MD in 1952, and together with husband Dr. Donald Merritt (IUSM's first chairman of the Department of Medical and Molecular Genetics) completed their residencies at Duke, she in pediatrics, he in internal medicine.
The couple's next move, to NIH, would shape her future. With no position available in pediatrics, she joined the Division of Research Grants, and there she found her niche. "It was marvelous," she recalls. "I worked with people famous in physiology and medicine. I loved listening as they critiqued studies from young investigators and advised how to improve their work. I couldn't have done any of that, but I could be a great facilitator and that's what I discovered I loved to do - to move things along!"
She got the opportunity in spades when the Merritts, now with two children, made the move to IUSM in 1961. Donald joined the Department of Medicine; Doris was named director of medical research grants and contracts.
It was an exciting time on a growing campus. Over the course of her career, Dr. Merritt would have a hand in changes that took the School from a quiet training ground for the state's physicians to a bustling medical research center on an intercollegiate campus. Between 1961 and 1978, she was instrumental in bringing $55 million in grants for new construction to the campus. As research joined education and service as a vital component of the School's mission, she provided administrative support as IUSM research dollars grew from $1.8 million in 1961 to nearly $105 million today. (Two program project grants written by medical researchers her first year at IUSM are still ongoing.)
These changes didn't happen overnight. "In 1961, you understand, we were in the dark ages," she says. "NIH grant applications were ten snap-out flimsies with carbon paper - try that on a manual typewriter! Well, I was the one signing off on these and I couldn't read them or make clear corrections. So I asked the assistant dean of finance if I could have an electric typewriter. He said absolutely not! If I get you an electric typewriter, the Dean's secretary Wilma will want a one and my secretary Judy will want one. So I wrote to Herman Wells, who was president of the IU Foundation, requesting an electric typewriter for my business dealing with grants, which were made to the IU Foundation at that time. What I didn't know was that the assistant dean served on the committee reviewing those foundation requests. So the first time he saw that request was in committee meeting, and they teased him unmercifully. He was rather provoked. I said, well you told me you wouldn't buy it, but you didn't say I couldn't try someplace else!"
She got the typewriter. (So did Judy and Wilma.) And although Dr. Merritt says her effectiveness comes from knowing how to move through channels and around them without arousing antagonism, her determination once led Dean Emeritus Walter Daly, MD, to call her "my dean who gets things done."
By her own account, the perfect assignment for Dr. Merritt was where someone had an imaginative new program but little idea of how to implement it. She became the first physician ever to be made an honorary member of the international nursing society Sigma Theta Tau, in recognition of her service as first acting director of the National Center for Nursing Research, NIH, when its establishment was mandated by Congress. As a Presidential appointee to the Board of Regents of the National Library of Medicine and its chair, she was a strong supporter of the efforts that created the infrastructure for the medical library electronic information systems used by all students and health professionals today. And as dean for research and sponsored programs, IUPUI, her entrepreneurial approach helped launch several ongoing community health and education programs such as the Consortium for Urban Education.
In 1995, when the Purdue School of Engineering and Technology, IUPUI, faced an emergency search for a new dean, its faculty asked Chancellor Bepko to draft Dr. Merritt to take the helm during the interim; Purdue later awarded her an honorary doctor of science degree. She became professor emerita in 1996 but recently returned briefly to help both IUPUI and IU develop a new framework for the continued strengthening of research and graduate studies in Indianapolis.
"I lived in an era that was absolutely parallel to the NIH's growth and the country's support of health research," she says. "Coming in at the beginning, I learned the players and the intricacies of the NIH review process, and how to fit them into the university world. This was an absolutely vital insight in helping people get things done.
"It turns out that all you really have to do is listen for the best ideas, help people articulate what they want to do, and plot how to make it happen. That's the fun of it! When what they're doing is worthwhile, they can take it all the way to the top."
IUSM is not typically thought of as a place that sends its doctors into orbit! But come January 1998 a graduate of the class of '82 will ride the space shuttle Discovery up to the Russian space station Mir for a four-month scientific expedition.
The expedition is a career highlight for which David Wolf, MD, (at right in photo) has been preparing for years. He will have spent about 15 months training for the Mir mission, much of that time in Star City, Russia's space program "factory town," learning the Russian language and space systems. But the preparation goes back much further, to 1974 when he entered Purdue's engineering school, already targeting his postgraduate mission, the Indiana University School of Medicine. It's been a long process, and Dr. Wolf senses all the planning, education and training are coming together now. "I've been here 15 years, and I feel like I'm just reaching my stride," Dr. Wolf says, sitting in his Houston office at NASA. Dr. Wolf is a synthesizer. He earned his degrees in engineering and medicine with a further goal in mind: bioengineering. "You have to handle and operate the equipment to really know how you want it to feel and behave," he says.
As a child watching the early American space missions and as a teen whose imagination was sparked by Star Trek, Dr. Wolf always had at least half an eye on NASA. The medical and engineering degrees would help him get there. So would his interest in flying. After IUSM he joined the Indiana Air National Guard as a flight surgeon - a move that got him into F4 Phantom jets. "Bioengineering was always my goal," Dr. Wolf says. "I liked flying, I liked engineering, I liked biology and medicine. And I liked space. There was only one place to do all of that at once. I'm kind of lucky; very few people find a job that wraps up all their professional interests, or lets them have multiple ones all at one time."
He joined NASA in 1983 and was selected as an astronaut in 1990. He started in NASA's Medical Sciences Division, helping develop an echocardiograph for use in space, and later helped design a bioreactor for growing tissue in three dimensions. He holds 11 patents on the device, and a version of it will fly to Mir with him. It's the second time Dr. Wolf will use in space equipment he has designed on the ground. His first space flight, a 14-day Spacelab mission in 1993, focused on human physiology and made use of his echocardiograph equipment.
Despite this summer's Mir crash, a fire and some balky equipment aboard the aging station, Dr. Wolf says he is comfortable with the notion of spending four months there, overseeing a couple dozen science experiments and performing space station chores while the earth turns 240 miles below. "It's inherently somewhat dangerous to fly in space, there's no doubt, but I think we've controlled those risks to a very manageable level," Dr. Wolf says. "Personally I enjoy working in those kind of critical situations. I'm ready to go up there and get what we can done."
(As of press time, Dr. Wolf was tentatively re-scheduled to launch September 25 aboard the shuttle Atlantis.)
October 10-12, 1997 Fall Medical Alumni Weekend Brown County Inn Nashville, Indiana
October 14, 1997 American College of Surgeons Reception for Alumni Chicago
October 17-18, 1997 Garceau-Wray Lectures University Place Conference Center Indianapolis
March 30, 1998 American College of Cardiology Reception for Alumni Atlanta, Georgia
May 15-17, 1998 Mark your calendar for Spring Medical Alumni Weekend! Class years ending in three and eight will celebrate reunions. Indianapolis
Please Note! The IUSM Alumni Association is producing an updated directory to be available May 1998. Complimentary copies will be provided to all current members. Be on the lookout in October for the first survey. For information on these events, please contact the Office of Alumni Relations at (317) 274-8828.