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Ann Arbor, Mich—At its landmark 150-year anniversary, the University of Michigan Medical Center is located on the same site where it was founded in 1850. Its modern boundaries are still defined on one side by the university's main Ann Arbor campus and on the other by the scenic parkland that surrounds the Huron River.
Howard Markel, MD, PhD, director of the university's Historical Center for Health Sciences, says that the medical center's physical location both symbolizes and contributes to its historical strengths and priorities. Its proximity to the university's diverse intellectual resources has fostered a spirit of multidisciplinary innovation. And its views of the open midwestern landscape speak of the medical school's long tradition of service to all of the state's residents, as expressed by its original mission to provide medical training for Michigan physicians and its early opportunities for women and minority students. These dual priorities continue to inspire innovations in medical education, clinical medicine, and basic research.
Men and women students at the University of Michigan Medical School practice bandaging and fracture dressing in the 1890s. (Photo credit: University of Michigan Medical School)
To recognize the medical school's sesquicentennial, this issue of JAMA contains an article about its history as well as several contributions on diverse topics from current faculty members.
Cyril Grum, MD, a professor in the Pulmonary Division of the Department of Internal Medicine, teaching students Tina Hahn and Kwabena Osei-Boateng (standing) and Wilmer Balaoing (seated). (Photo credit: University of Michigan Biomedical Communications)
The Medical Readiness Trainer (MRT), which continues to undergo development in a joint project of the University of Michigan and Old Dominion University in Norfolk, Va, provides a programmable virtual reality educational experience; it was recently included in a Smithsonian Institution time capsule. Dag von Lubitz, PhD, assistant professor in the Department of Emergency Medicine, said the MRT represents the successful integration of four technologies: human patient simulators, three-dimensional imaging, the second-generation Internet, and rapid synchronous video streaming.
Von Lubitz's group has developed a lifelike patient simulator that can be programmed to present a wide range of traumatic injuries and physiological derangements. Trainees need not even be in the same room as the simulator; with carefully placed pairs of cameras, convincing three-dimensional video images of the simulator and its surroundings can be projected on a three-dimensional screen, where trainees can interact with it in real time.
Furthermore, the team has developed a number of immersional visual environments where students may interact with the simulator. In addition to a simulated emergency department (with real-life noises and distractions), they can be placed in the sick bay of a pitching virtual Coast Guard cutter or a virtual medical evacuation helicopter.
The team hopes to further enhance the immediacy of the experience by developing an "odor palette" that will permit realistic and unpleasant odors to be sprayed into the trainee's nostrils at the appropriate moments. Von Lubitz said that his ultimate goal is to provide realistic but structured training that can now be obtained only under unpredictable field conditions with living patients. He added that the virtual sick bay experience is so compelling that new trainees frequently become seasick.
The simulator team has begun a joint venture with the University of Puerto Rico to deliver this technology to a facility that cannot afford to provide advanced training on its own. Medical trainees in Puerto Rico can interact with the simulator in Michigan, which can be controlled by a preceptor in yet a third location. Von Lubitz said the team is now developing a pair of small video cameras that can be mounted on either side of a surgeon's head. The device would provide a 3-dimensional surgeon's-eye view of procedures performed on real patients, thus allowing any number of trainees anywhere in the world, even those without access to advanced medical technology, to learn from experienced surgeons.
This outreach, said von Lubitz, is fundamental to Michigan's educational mission. Additional details can be found at http://www-vrl.umich.edu/mrt.
Strength in surgery
The MRT has benefited from the strength of Michigan's surgical programs. Under the direction of John Alexander, MD, the University of Michigan Medical School developed the first US residency program in pediatric cardiothoracic surgery. By the 1950s, surgeons were routinely repairing congenital cardiac defects in infants as small as 2 kg.
Edward L. Bove, MD, the current head of the Section of Cardiac Surgery, said he leads a "uniquely talented" group that performed 860 cardiac procedures last year, including repair of hypoplastic left ventricles, valve replacements, and complete heart transplantations in infants as early as the seventh postpartum day. Bove attributes much of this success to a multidisciplinary approach that requires accurate intrauterine diagnosis as well as advanced medical and nursing support throughout the complicated postoperative course.
Having performed more than 50 successful procedures, the Michigan surgery department is now one of the most experienced in the world in repairing the hypoplastic left ventricle, a lesion that is fatal without surgical intervention. A recent retrospective study of 3- to 6-year-old patients found that despite the threat of chronic hypoxemia, most had reassuringly normal developmental outcomes. Bove said most of these patients also experience atrial arrhythmias as a consequence of surgery, and the department is examining ways to manage this complication with both prospective studies of surgical technique and computer modeling. Patients are also benefiting from computer modeling of flow dynamics through the hypoplastic ventricle, which allows predictions of the effects of fine variations in surgical technique.
Gene therapy has begun to augment traditional surgical approaches at Michigan. For instance, researchers here are exploring whether transfection with genetically altered adenovirus may protect infants' immature myocardium from damage by free radicals. Future repair of the hypoplastic ventricle may involve placing a temporary scaffolding over the defect and then inducing autologous myocardium to grow over it, essentially allowing surgeons to help the patient grow a new ventricle.
Genetics research has a long history at Michigan, which established the first Department of Human Genetics in a US medical school. Treatment of dysfunctional muscle is a current interest at the school's Center for Gene Therapy, which is directed by Jeffrey S. Chamberlain, PhD. Chamberlain's group has focused on the treatment of Duchenne muscular dystrophy, for which there is no currently available therapy. The disease is caused by a mutation of the dystrophin gene, which codes for a structural protein in skeletal and cardiac muscle. Because muscle tissue replicates slowly, delivery of a functional dystrophin gene to sarcomere nuclei theoretically could provide long-lasting expression of the protein, resulting in normal muscle phenotype.
In a mouse model of muscular dystrophy, Chamberlain's multidisciplinary group has been able to deliver instructions for normal dystrophin by replacing most of an adenovirus genome with the dystrophin gene. These "gutted" viruses maintain infectivity but, because they contain none of the original viral sequences, they do not appear to stimulate an immune response. The gutted viruses are injected every few millimeters into mouse muscle, where the adenoviruses deliver the dystrophin gene into sarcomere nuclei.
Treated mice have been found to express the dystrophin protein for several weeks and to have an essentially normal phenotype despite their underlying genetic disease, even if they had previously displayed significant muscle weakness. In the host nucleus, the dystrophin gene appears to come under control of local regulatory proteins and does not appear to be expressed in transfected nonmuscular tissue.
Despite these very promising results in treating a disease that has long been considered hopeless, Chamberlain says several technical challenges remain to be overcome before the therapy can be applied to humans. The most significant of these are development of methods for generating large amounts of pure gutted virus and creating a systemic delivery system that would bypass hepatic degradation.
Beyond the study of single-gene diseases, researchers at the Center for Gene Therapy are attempting to unravel the interplay of large groups of unrelated genes. Such complex systems appear to underlie many common age-related disease phenotypes such as hypertension, coronary heart disease, and obesity. An understanding of the genetic basis of these diseases could yield treatments that address their fundamental origins.
Lurie S. Innovation and Service Traditional at University of Michigan Medical School. JAMA. 2000;283(7):865–866. doi:10.1001/jama.283.7.865
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