Marion David Francis: 1923–2016 (2016)

Marion David Francis “Dave” Francis, our cherished friend and colleague, died on May 10, 2016, a day after his 93rd birthday. He made major scientific discoveries in the dental and medical fields that improved the lives of millions of people around the world. Dave was born in Vancouver, Canada, gained his Bachelor's degree in physics and chemistry at the University of British Columbia (UBC) followed by a Master's degree in analytical chemistry at UBC and a doctorate in biophysical chemistry at the University of Iowa in 1951. In 1952, he joined the Procter and Gamble Company (P&G) at the Miami Valley Laboratories in Cincinnati, OH, USA, where he spent most of his professional career, publishing over 100 papers and 35 patents. Dave's early work was in the area of dental research. His basic research on the chemistry of tooth enamel structure and formation and of the mechanism by which fluoride ions interfere with the destruction of tooth enamel and dentine helped to lay the scientific foundation for the effective use of fluoride to prevent caries.1 The widespread adoption of fluoride therapies resulted in a more than 70% reduction in the incidence of dental caries among children from 1967 to 1988. As a testimony to the significance of this work, P&G received special recognition from the American Dental Association for the prevention of dental caries. P&G's Crest® and many other fluoride-containing toothpastes continue to be in use more than 50 years later. Dave extended his work on tooth enamel to the thermodynamics of the calcium phases of calcium salts, important in controlling the formation of hydroxyapatite, with a view to preventing dental calculus and plaque. He demonstrated the potential of polyphosphonates2 to influence these processes, as had previously been shown for pyrophosphate. This led to collaboration with Herbert Fleisch and Graham Russell in Davos and Bern in Switzerland, resulting in the first recognition of the important biological effects of the chemically stable bisphosphonates (then called diphosphonates) in the prevention of calcification and bone resorption. This collaborative work was reported in two landmark papers in Science in 1969.3, 4 After this, Dave played an important role in enabling the early clinical use of bisphosphonates, particularly etidronate and clodronate, which resulted in P&G eventually marketing etidronate as Didronel®, and becoming a Pharma company. Notably in 1967, he collaborated with Dr. Andrew Bassett, a physician at Columbia-Presbyterian Medical Center, on the first use of etidronate to treat a 16-month-old child with fibrodysplasia ossificans progressiva.5, 6 Another of his long-lasting contributions to medicine was in the development of radiolabeled bisphosphonates to detect abnormal metabolic bone activity.7-10 The use of 99mTc-labeled bisphosphonates was first commercialized (Osteoscan®) at P&G, and these 99mTc-labeled reagents continue to be used for bone imaging until the present day. Key collaborators in these developments were Ignac Fogelman, Andy Tofe, John Bevan, Jim Benedict, Bobby Barnett, and Larry Flora. Dave vigorously eschewed managerial roles and remained actively engaged in laboratory science until his retirement in 1993. When challenged on this choice he commented, “I used to feel guilty that I was having so much fun in my lab work and getting paid for it.” He continued his research and consulting on the latest generation bisphosphonates11 well into his 80s and always found time to mentor new researchers in the field.12 His insights in physical chemistry continued to inspire chemical creativity with new bisphosphonates and the defining of structure-activity relationships in the research led by Hal Ebetino and colleagues. Dave derived great pleasure and satisfaction from the clinical success of the bisphosphonates, which came to be used in treating a range of bone resorption disorders including Paget's disease, osteoporosis, hypercalcemia due to malignancy, and bone related morbidity due to metastases.13 His experimental work pointed to several other areas of potential use, such as cardiovascular disease and arthritis,14 applications that still remain to be fully explored. For these significant achievements, he was honored on several occasions by the American Chemical Society, receiving the Industrial Chemistry award in 1994, the Perkin Medal in 1996, and the “Hero of Chemistry” award in 2000. In 2003 he received the Distinguished Alumni Award for Achievement from the University of Iowa. He was also honored by election to the prestigious Victor Mills Society at the Procter and Gamble Company, in recognition of attaining the highest level of scientific achievement. He was a keen sportsman throughout his life, and his repertoire included skiing, squash, table tennis, golf, and tennis. Dave led an exemplary life and was loved and respected by his family, and by his many friends and professional colleagues. He enhanced many lives through his inventions and shared his talents and love of life with all around him. F Hal Ebetino Department of Chemistry, University of Rochester, Rochester, NY, USA R Graham G Russell Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK David J Valent Procter & Gamble, Mason, OH, USA Nelson B Watts Osteoporosis and Bone Health Services, Mercy Health, Cincinnati, OH, USA