Gregory Robert Mundy 1942—2010

On February 25, 2010, the bone and mineral research community lost a superstar. Greg Mundy, who succumbed to a malignant brain tumor, held the John A. Oates Chair in Translational Medicine at Vanderbilt University, where he was recruited in 2006 to develop its Center for Bone Biology. He was also Professor of Medicine, Pharmacology, Orthopedics, and Cancer Biology.Scientists are fortunate in that our most direct competitors often become our closest friends, and so it was with Greg and me. We met in the late seventies, when we were each chasing the ontogeny of the osteoclast, whose hematological origin was not yet established. We both suspected the monocyte/macrophage was central to the cell's development and competed ferociously to solve the mystery. Amidst the competition, we discovered we liked one another, and our relationship evolved into a friendship that went beyond science. We often visited each other with our spouses and vacationed together. Greg, my competitor, became one of my best friends.There was a grace about Greg. He was modest and had the capacity to make his point in a nonconfrontational, good-natured manner. He considered teaching his most important responsibility, and, as such, trainees flocked to him. Greg mentored in excess of 150 students and postdoctoral fellows, many of whom now hold distinguished academic positions. At the same time, his charisma and clarity of delivery made him the most engaging of speakers at conferences. Students and young investigators sought his company and advice. Never disappointed, they were impressed by his warmth and recollection of previous chats regarding their research.Greg grew up working on a peach farm his family had carved out of the Australian outback in the mid-19th century. The environment was not conducive to higher education, and sequential generations of Mundys committed themselves to servicing the land. When Greg's parents became aware of his academic potential, however, they provided him with exceptional schooling. He not only was an extraordinary student at secondary school and Melbourne University, where he received his Baccalaureate in Medicne and Surgery, but became one of Australia's most competitive cricket players, twice winning the University's Cricket Club bowling average.While his interests were broad, Greg's passion was to understand the mechanisms of skeletal destruction in patients with cancer. He did so by marrying the disciplines of tumor and bone cell biology. Greg's interest in this issue harkened back to the early seventies, while completing his Doctor of Medicine degree at the University of Tasmania. During his thesis work on the cytogenetics of multiple myeloma, he realized little was known about the means by which this hematological malignancy destroys bone, a question he pursued the rest of his life. In 1972, Greg, his wife Helen, and three small children left Australia to join the laboratory of Lawrence Raisz at the University of Rochester. Larry had developed an organ culture model to assay bone resorption in vitro, and provided evidence that marrow cells, particularly macrophages, produce an osteoclast activating “factor” that Greg ultimately proved to be regulated by prostaglandins. At the same time, he discovered that the products of osteoclastic bone resorption are chemotactic to cancer cells, an observation that laid the foundation for the “viscous cycle of tumor osteolysis,” the contribution for which Greg will likely be most remembered. This model holds that the skeletal lesions of metastatic cancer, which reflect the activity of tumor-recruited osteoclasts, ultimately stimulate tumor growth and additional bone destruction. This series of observations provided the rationale for treating tumor osteolysis by antiosteoclastic drugs, particularly bisphosphonates, whose effectiveness Greg was first to demonstrate in animal models. Consequently, these agents are now standard therapy in malignant skeletal disorders such as myeloma and metastatic breast cancer.View Large Image | View Hi-Res Image | Download PowerPoint SlideIn 1980, eight years after his appointment as Research Associate in the Raisz Laboratory, Greg was recruited to serve as Professor and Head of the Division of Endocrinology and Metabolism at the University of Texas Health Science Center, San Antonio, where his major contributions came to fruition. Here he built one of the world's premier bone biology programs, ultimately holding the Heyser Chair in Bone and Mineral Metabolism.Realizing the potential importance of newly discovered growth factors and cytokines in skeletal homeostasis, Greg established that transforming growth factor β is abundant in bone matrix and chemotactic to osteoblasts. He also determined the potential importance of parathyroid hormone-related protein in the pathogenesis of breast cancer-induced osteolysis. These experiments provided an important rationale for his viscous cycle of bone metastasis hypothesis, and proved fundamental to understanding the coupling of osteoblast and osteoclast function that characterizes skeletal remodeling. Greg also provided insights into the relationship of newly discovered inflammatory cytokines such as tumor necrosis factor and interleukin-1 to osteoclast function in hypercalcemia of malignancy. Within the last decade, Greg established a potential role for statins and proteosome inhibitors as anabolic agents in the treatment of osteoporosis. A masterful writer, Greg published in excess of 500 scientific papers.More than any other member of our discipline, Greg Mundy was the paradigmatic physician-scientist. While focusing on understanding the fundamental mechanisms of bone cell biology, his ultimate goal was improved patient care. His translational commitment resulted in the awarding of 34 patents and the founding of 2 biotechnology companies and key participation in 2 others.Greg's stature and dedication to our community is reflected in the many awards and leadership positions he held. He served as president of our foremost societies including the American Society for Bone and Mineral Research and the International Bone and Mineral Society. He served on the editorial board of many journals, including Cell Metabolism. He was an NIH MERIT awardee, and for more than 20 years, principal investigator of a program project grant focusing on cancer and bone that remained funded until his death.Greg died as he lived. He refused to surrender and, until terminal, participated in experimental design and laboratory meetings via computer video link from his home. I spoke to him often during his last days. He laughed and reflected on his many good times with family and friends. He abjured self-pity, and his concern was always the welfare of others, particularly the team of young investigators he recruited to build the Bone Center at Vanderbilt. While it is a cliche to claim someone irreplaceable, Greg Mundy is.I thank David Roodman and Brendan Boyce for their comments.