In Memoriam: The Life and Works of Itai Bab (1945–2014)

Itai Bab was born on May 10, 1945, in Rehovot, Israel, as the only child to Hasida and Rudolf-Natan Bab. Rudolf came from Germany in the 1930s escaping the emerging Nazi threat, whereas Hasida was a fifth generation Israeli of Russian descent. Itai was recognized by his peers and family as a bright and diligent student, aside from being proficient in handball. His father passed when Itai was 16 years old, and, at age 18 years, he was recruited to serve in the Israeli Defense Forces' (IDF) Engineering Corps. Upon discharge, Itai began his academic education in statistics and international sciences, and went on to obtain a Doctorate of Dental Medicine from the Hebrew University. In 1976, he was recruited as an instructor in the Department of Oral Pathology at the Dental School and rose through the ranks to become tenured professor in 1994. Beginning in 1992, he served as Chief of the Bone Laboratory, which he founded, and held several senior administrative roles at Hebrew University. Itai's interest in bone biology, which culminated in several "firsts," arose initially from a 2-year stint at Maureen Owen's laboratory in Oxford in 1982, followed by an equally productive sabbatical with Gideon Rodan at Merck in 1987. At Oxford, while cell and molecular biology was in its infancy, Itai began to define the genetic and phenotypic characteristics of bone marrow stromal cells. Laying the foundation of how bone marrow stromal cells are controlled, he characterized, using diffusion chamber cultures, among the first known regulators of osteogenesis—osteogenic growth peptide (OGP). Numerous subsequent studies by Itai and his many colleagues established the structural requirements for the mitogenic action of OGP. Molecules based on this discovery are currently used to assist the bridging of human skeletal defects. Itai's more recent contributions centered round the brain-bone connection. In a seminal paper in 2005, he described, for the first time, an effect of centrally administered interleukin-1 on bone. He then definitively established the presence of a skeletal cannabinoid (CB) receptor and studied the role of lipid compounds in bone mass regulation. Of particular relevance was evidence for the modulation of sympathetic signaling in bone by the CB1 receptor and its ligand, 2-arachidonoyl-glycerol. This latter mechanism appears involved in the stimulation of bone formation following traumatic brain injury, a longstanding and unresolved clinical dogma. On the clinical front, Itai and colleagues conclusively established depression as a risk factor for osteoporosis, a finding that has worldwide medical significance considering the overall prevalence of this disorder. Indeed, as a fine example of reverse translation, he showed for the first time that experimental depression causes bone loss. Itai not only provided epic insights into mechanisms of skeletal remodeling, but also made an enduring impact on our understanding of skeletal microanatomy. The Micro-Tomographic Atlas of the Mouse Skeleton remains a classic. It describes in detail, and with over 2000 images, all the features of the mouse skeleton. With the mouse being the most utilized animal in skeletal genetics, this book continues as a primary reference standard for researchers in bone biology, orthopedics, motion analysis, zoology, and biotechnology, among others. Itai, nonetheless, never lost touch with dental research. In recent years, he proudly published key papers on the anchorage of endo-osseous implants by analyzing the structural determinants critical for implant stabilization. Using state-of-the-art image-guided failure assessment, Bab defined the relationship between peri-implant bone structure and an implant's biomechanical function. Using his structure/function approach, he also emphasized the usefulness of bone anabolic agents in enhancing endo-osseous implant anchorage. Itai remained a true proponent of interdisciplinary science, which he stretched to its most valuable limits with the help of his long-standing mentor, colleague, and friend Professor Raphael Mechoulam. In 2007, he organized a NeuroPsychoOsteology Workshop, which brought together leaders in skeletal medicine, neuroendocrinology, cannabinoid research, and neuropsychiatry. This truly interdisciplinary forum was followed by an equally elegant workshop, Cannabinoids in Biology and Medicine 2010, where Itai focused on multidisciplinary facets of the emerging bone-brain axis. Together, these conferences seeded novel areas of investigation for a generation of scientists; these areas continue to be nurtured. Itai's contributions to our field, and to integrative physiology and translational biomedical research most generally, have been profound and broad-ranging. His discovery of the skeletal cannabinoid system stands out not only because Itai courageously integrated two entirely unrelated disciplines, but also because of the apparent promise the CB2 signaling pathway holds as anabolic therapy for osteoporosis. And, now to the human face of Itai Bab. The most important thing, according to his wonderful wife, Tsippi, was Itai's "desire to love and to be loved." His passing, as one would expect, thus came as shocking news—not only to many of his close friends and colleagues, but also to our bone community at large. What continue to resound, however, are not only his exceptional contributions to our field, but his wisdom, manner, generosity, friendship, and above all, his profound humility. He leaves behind a wonderful family—Tsippi, whom he married 41 years ago when they were both students in Jerusalem, their three accomplished children Avi, Natti, and Omer, and five young grandchildren. Painful as Itai's loss is to all of us, on behalf of his friends, colleagues, and the bone community, we offer the family our deepest condolences. Mone Zaidi Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA Clifford Rosen Maine Institute for Medical Research, Portsmouth, ME, USA Alberta Zallone Department of Histology, University of Bari Faculty of Medicine, Bari, Italy

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