Gabriele Zu Rhein, M.D.
Madison - Dr. Marie Gabriele Freiin Zu Rhein was born to Ludwig Freiherr Zu Rhein and Maria Therese Freiin von Bleul in Munich, Germany on April 5, 1920, and died at Oakwood Village University Woods on February 23, 2016, at the age of 95. Gabriele descended from a Swiss-German family that was granted nobility, which bestowed upon her the title of Baroness (Freiin). She pursued the study of Medicine at the Ludwig-Maximilians University in Munich from 1939 to1945. Her preclinical years coincided with the start of World War II, and in 1943, Allied bombings required Gabriele to spend many hours studying in air raid shelters and later in a mineshaft. After her medical school education was completed, she began a residency in Pathology at the Schwabinger Krankenhaus hospital in Munich.
When the American Army occupied Munich in May 1945, the U.S. 98th General Hospital took over the Schwabinger. Conversant in English, Zu Rhein was offered the position as Assistant Chief of Laboratory Service, a position she held for 8 years. During this period of post-graduate education, she was fortunate to receive personal instruction from many American doctors in the 98th who had been university professors at major U.S. medical schools. In addition, several professors from German medical schools came to the 98th General Hospital to give instruction in neuropathology, a subspecialty that was to become Dr. Zu Rhein's major field of practice and research.
During the post-War period, the activities of the 98th General Hospital were scaled down, and Gabriele looked for other professional opportunities. Fortuitously, one of the U.S, doctors, who had been at Yale wrote Gabriele that he had moved to Madison to become Professor and Chairman of the Department of Preventive Medicine. He told her of a job in the Department of Pathology and recommended her to the department chairman. She accepted an appointment and came to Madison in 1954 to begin a remarkable 41-year career at the University of Wisconsin until her retirement in 1995. Her responsibilities included teaching medical students and performing autopsies. Shortly after her arrival, the professor who carried out the brain examinations left the department, and Gabriele was assigned this activity.
Since her experience in neuropathology was limited, Gabriele was forced to become self-taught by reading German and later English texts as they became available. Dr Hans Reese, a native of Germany and the Chair of Neurology, gave her additional books and journals to study. He also permitted her to use his lab technician for special stains necessary for microscopy. Zu Rhein benefitted by having a large source of cases from the Wisconsin General Hospital (now the University of Wisconsin Hospital) and from Wisconsin Central Colony (now Central Wisconsin Center) and from around the State. She also gained experience by attending conferences of neurology and neuropathology societies. In 1964, Gabriele was granted a one-year sabbatical to study with Dr. Harry Zimmerman in New York, where she became proficient in electron microscopy.
Zu Rhein's career flourished as a diagnostic neuropathologist and teacher. She also taught students in Veterinary Science and Allied Health. Residents in Pathology, Neurology, and Neurosurgery also took rotations in neuropathology during their training. With this enormous burden as a diagnostic neuropathologist and teacher, Zu Rhein had little time for any basic research. It is quite remarkable then that in 1962 she embarked on a research career that resulted in making revolutionary discoveries involving infectious agents as the cause of degenerative brain diseases.
In 1962, Zu Rhein received a brain consultation regarding a degenerative disease. A post-doctoral student in the Department thought that the microscopic changes resembled those of a newly described condition called Progressive Multifocal Leukoencephalopathy (PML). Shortly thereafter, a second case was found at the University. When she examined ultrathin sections from these cases using the electron microscope, Zu Rhein observed crystalloid aggregates similar to those seen in tumors called papillomas in dogs, caused by DNA viruses. No virus of this type was known to infect humans. A well-known microbiologist had recently described a new category, the Papova Virus Group, combining the Papilloma and Polyoma DNA viruses, both capable of producing tumors in animals. Experts in the field agreed with Zu Rhein that her interpretation of the presence of viruses was correct.
In 1966, Dr. Zu Rhein began participating with other investigators studying "slow viruses," diseases that are defined by their long incubation and slow progression. At Wisconsin, she started a long, fruitful collaboration with a virologist in the Department of Medical Microbiology, Dr Duard Walker, and his Research Associate, Dr. Billie Padgett. Using human fetal brain tissue culture, they were able to isolate viruses from brain tissue of a patient who died with PML. The virus was called the JC virus, using the initials of the patient. JC virus was later isolated from PML cases by other scientists. Electron microscopy also showed that the virus targeted cells in the brain whose destruction results in the loss of myelin sheaths that protect nerve cells.
Remarkably, in 1973 Gabriele embarked on a new phase of her career after obtaining an NIH RO1 grant to study viral pathogenicity in animals. She injected newborn hamsters with JC virus, and after four months, hamsters started dying from primary brain tumors. This demonstrated that a human virus that causes a degenerative brain disease in humans can also produce brain tumors in animals. No demyelinating disease was observed in the animals. In recognition of her achievements in research and her exemplary devotion to her discipline, in 1977, Dr. Zu Rhein was elected President of the American Association of Neuropathologists. She authored and co-authored dozens and dozens of articles for scientific various journals.
After her retirement in 1995, Zu Rhein continued to lecture in neuropathology. She also assisted the Department of Pathology Chairman with his responsibilities as Editor of the Journal of Neuropathology and Experimental Neurology. Gabriele continued her interest in demyelinating diseases and spent many hours at the electron microscope. In the 1990s she was sent a presumed case of PML that showed unusual changes including proliferation of endothelial cells in capillaries near the areas of demyelination. Further studies identified a small bacterium known as Mycoplasma pneumoniae in brain cells in the region. This second discovery was the crowning achievement of a long, brilliant career.
Gabriele is survived by her brother, Hans Herterich Freiherr Zu Rhein von Bleul, in Munich, Germany, as well as her nephew, Hugo Maximilian Freiherr Zu Rhein von Bleul (Patricia) and their son, Ludwig Amadeo in Munich; and her niece, Felicitas Freiin Zu Rhein von Bleul (Wolfgang Helm) and their children, Valerie-Charlotte, Alexander and Marquard in Ochtrup, Germany.
Gabriele was preceded in death by her parents, her infant sister Mechthilde in 1926, and her sister-in-law Editha (Engel) Freifrau Zu Rhein von Bleul in January 2016.
Special thanks to Tabor-Oaks Assisted Living, especially nurses Wendy, Carla and Susan and the staff on the second floor, for their care of Gabriele during her last year. Burial will be in Munich, Germany. A memorial service with friends and colleagues will be held at a later time. In lieu of flowers, contributions may be made to the UW Foundation, Olbrich Botanical Gardens and Wisconsin Public Radio. Aufwiedersehen Gabriele.
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