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					                Journal of Dental Research

Roy C. Page: Leader in Collaborative and Multidisciplinary Research in Periodontology
                             S. Bordin, A.S. Narayanan and P.B. Robertson
                                       J DENT RES 2008 87: 293
                                  DOI: 10.1177/154405910808700419

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                                                 International and American Associations for Dental Research
 Martin Taubman, Editor

S. Bordin1*, A.S. Narayanan2, and P.B. Robertson1
                                                                                               Roy C. Page: Leader in
1Department  of Periodontics, School of Dentistry, and 2Department of
Pathology, School of Medicine, University of Washington, Seattle, WA
98195, USA; *corresponding author,
                                                                                               Collaborative and
J Dent Res 87(4):293-295, 2008                                                                 Multidisciplinary Research
                                                                                               in Periodontology

In a career spanning pathogenesisresearch contributions to has
                     four decades thus far, Dr. Roy Page                                       disciplines and internationally respected mentors was
 made unique and transforming                              the                                 remarkable.
understanding of the              and clinical management of                                       Dr. Page formed a group that included Dr. Sampath
the periodontal diseases. Along the way, Dr. Page became an                                    Narayanan and a host of graduate students to describe the
avid enthusiast of classical opera. In Roy's view, the strength                                localization and distribution of the various collagens and
of any opera performance was less a function of an individual                                  proteoglycans that comprise the healthy and diseased
conductor or soloist or cast member, but rather the creative                                   periodontium (Narayanan and Page, 1976). Their laboratory
collaboration that brought out the best in all members of a                                    was the first to demonstrate that collagen turnover in the
multidisciplinary ensemble. Such a collaborative and                                           periodontium is far more rapid than in other normal connective
multidisciplinary approach to research and clinical excellence                                 tissues. Dr. Sandra Bordin joined them to provide evidence that
is reflected in a career that includes six textbooks and                                       multiple genetically stable varieties of fibroblasts exist in
monographs, and more than 300 journal publications and book                                    normal gingiva and gingival granulation tissue (Bordin et al.,
chapters. Approximately 90% of Page's journal publications                                     1984). A unique fibroblast phenotype was isolated and
are authored by an average of four other investigators. A                                      characterized based on ligand binding to the high-affinity C1q
review of the co-authors of his publications and abstracts                                     complement receptor. Research with dental students identified
identifies more than 800 unique collaborators with diverse                                     a component of root cementum that communicated with and
disciplines and institutional affiliations, the majority of whom                               regulated fibroblasts in their vicinity. Dr. Page suggested that a
serve as first author of the publications. The National Institutes                             repertoire of fibroblasts may exist in small numbers in all
of Health records place him above the 95th percentile of                                       normal connective tissues, and that the cell type that becomes
extramural grants, obtained primarily through collaborative                                    dominant in a tissue is determined by normally occurring
Center and Institute initiatives funded during the past 25 years.                              mediators that stimulate proliferation of a specific
We are among many others who have been profoundly and                                          subpopulation, or by drugs such as diphenylhydantoin. A series
positively influenced by Roy Page's intellectual insight,                                      of early clinical studies in periodontitis patients concluded that
nurturing support, extraordinarily high standards of excellence,                               prostaglandins and several cytokines were critical
and solid friendship. We have discussed Roy Page's journey of                                  inflammatory mediators in the pathogenesis of periodontitis.
discovery with a broad range of his colleagues and friends. We                                 Related observations also showed that specific serum
take great pleasure in reflecting their views of his fundamental                               antibodies to antigens of pathogenic bacteria could block
contributions to oral biology and clinical periodontology.                                     prostaglandin production by mononuclear cells. Dr. Page also
    Page established a distinguished record of undergraduate                                   suggested a potential role for specific antibody suppression by
scholarship at Berea College in Kentucky and graduated                                         immunization in controlling alveolar bone loss.
Summa Cum Laude from the University of Maryland School of                                          The early 1970s marked the beginning of what colleagues
Dentistry. He entered the Experimental Pathology PhD                                           smilingly term "Roy's white linen suit period", owing to
program, led by Dr. Earl Benditt, and Periodontics specialty                                   multiple copies of the same tailored suit worn at all meetings.
training with Dr. Saul Schluger at the University of                                           He began to focus on relationships among the oral microbiota,
Washington in 1961. He completed this formative period with                                    the inflammatory infiltrate, and destruction of the connective
Dr. Anthony C. Allison at the Medical Research Council                                         tissue matrix in multiple forms of periodontitis. His
Laboratory in London. The resulting convergence of                                             collaborative group expanded to include national and
                                                                                               international investigators, and his laboratory became filled
                                                                                               with basic and clinician scientists, residents, post-doctoral
                                                                                               fellows, and dental, medical, and graduate students.
                                                                                               Conversations with those involved with Dr. Page's group at the
KEY WORDS: periodontology, oral biology, periodontal                                           time universally remember Roy as a warm and genial host, a
connective tissue, matrix, clinical trials.                                                    connoisseur of fine food and wine, a rigorous debater long into
                                                                                               the evening, and an intellectually fearsome critic. His office
Received February 2, 2007; Last revision December 21, 2007; Accepted                           was unpretentious at best, filled to overflowing with boxes of
January 3, 2008                                                                                reprints and manuscripts, unstable furniture, a single line phone

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                                                             International and American Associations for Dental Research
294                                                                           Bordin et al.                                                           J Dent Res 87(4) 2008

                                                                                             saw development of a vaccine for human periodontitis as a
                                                                                             realistic goal. They identified and partially characterized the
                                                                                             predominant antigens of periodontal pathogens and assessed
                                                                                             antigenic variation and cross-reactivity among isolates of these
                                                                                             species. They characterized the humoral immune responses of
                                                                                             normal subjects and periodontitis patients to these same
                                                                                             bacterial species, including serum antibody titers, avidity and
                                                                                             other functional characteristics, IgG subclass distribution,
                                                                                             opsonic activity, and the effects of periodontal therapy on
                                                                                             immune responses. Based on these studies, Page and his
                                                                                             colleagues developed and began testing a vaccine for human
                                                                                             periodontitis using ligature-induced periodontitis in Macaca
                                                                                             fascicularis as a model. Repeated trials showed that
                                                                                             immunization reduced alveolar bone loss about 50% relative to
                                                                                             controls. Total bacterial load, levels of putative bacteria in the
                                                                                             subgingival flora, and levels of PGE2 in gingival fluid were
with all the numbers worn from the keypad, and an electric                                   significantly reduced. Page and his co-workers concluded that
typewriter for which replacement parts were no longer                                        the dramatic results in this animal model were related to
available. It was a place for students, faculty, and distant                                 antibody-mediated phagocytosis and killing of key pathogens,
visitors to feel welcome while engaging in spirited discussions                              with concurrent suppression of cytokines mediating connective
on new approaches to research mixed with deliberations on the                                tissue and alveolar bone destruction. More importantly, the
proper age of wine, the proper care of tomato plants, or a recent                            series of studies in non-human primates firmly established a
opera performance. The result of his collaborative efforts to                                possibility of immunization for human periodontitis.
understand the biology and clinical management of the                                            Dr. Paul Robertson arrived as dean at the University of
periodontal diseases were summarized in what has become a                                    Washington in 1991. Page was establishing a Regional Clinical
citations classic (Page and Schroeder, 1976) and a subsequent                                Dental Research Center with support from the National
monograph on periodontitis in humans and other animals (Page                                 Institute of Dental and Craniofacial Research. In addition to his
and Schroeder, 1982). These concepts were broadened and                                      international collaborators, Page also involved the majority of
updated in a subsequent monograph on the pathogenesis of                                     faculty in the School of Dentistry and a broadly
periodontitis (Page and Kornman, 1997). In what reads like                                   interdisciplinary group of investigators from departments
vigorous conversations between colleagues, these works                                       throughout the university, particularly the Schools of Medicine
postulated that periodontitis reflected the sum total of                                     and Public Health. The Center was engaged in numerous
interactions among highly organized oral bacteria, the                                       randomized clinical trials on the diagnosis and treatment of
periodontal tissues, and a broad variety of host defense                                     periodontal diseases, including the development of techniques
systems. The work further argued that periodontitis was neither                              to measure disease activity at specific periodontal sites,
linear nor an automatic consequence of gingivitis, and could                                 efficacy and safety of anti-inflammatory agents, and
assume numerous clinical presentations depending on the                                      therapeutic utility of antimicrobial therapy. From a dean's
nature and effective radius of the infecting bacteria, periodontal                           perspective, Page had for years brought great distinction to the
anatomy, genetic predisposition, and expression of the host                                  university, in general, and to dentistry in particular. He held
inflammatory response. Critical variables also included the                                  professorial appointments in Pathology within the School of
size, location, and composition of the biofilm, the frequency                                Medicine, and Periodontics within the School of Dentistry. He
and duration of epithelial ulceration, the everyday habits of the                            had earned independent funding from the public and private
host, and the regularity of oral care. Dr. Page proposed a family                            sectors for three decades. He had been elected by peers to the
of different but related clinical forms of periodontitis, including                          presidency of both the American and International Associations
prepubertal and rapidly progressing forms, having features in                                for Dental Research. The work of his collaborative group had
common but being distinctly different entities in terms of                                   fundamentally influenced the study and the practice of
etiology, pathogenesis, progression, natural history, and                                    Periodontics. Thus, it was not surprising for the new dean to
response to treatment. Later deliberations focused on the                                    learn that Roy was also an outstanding faculty member and a
iterative nature of the bacterial challenge and host cellular                                solid University citizen. He taught the major courses on basic
response in periodontitis, a process postulated to be highly                                 and systemic pathology to generations of dental students. Other
regulated and in constant adjustment. The discussion                                         teaching activities included courses in anatomy, pathology, and
substantially influenced classification schemes subsequently                                 human biology for medical, pharmacy, and multidisciplinary
adopted by the American Academy of Periodontology. At the                                    graduate students. Students characterized him as an articulate
same time, Dr. Page held that periodontal classifications were                               and highly organized instructor with high standards of
temporal, and must invite scientific inquiry and necessarily                                 expectation combined with a clear concern for their educational
evolve to reflect new research findings. He recently added to                                needs. He willingly brought his extraordinary insight and
the classification evolution by describing case definitions for                              meticulous preparation to a wide range of dental school and
periodontal diseases that are to be used by the Centers for                                  university committees.
Disease Control for population surveillance of periodontitis                                     During the last decade, Page and his colleagues have
(Page and Eke, 2007).                                                                        embarked on projects to improve the quality and design of
    Beginning in the early 1990s, Dr. Page and his co-workers                                clinical trials in Periodontics, improve the precision of

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                                                            International and American Associations for Dental Research
J Dent Res 87(4) 2008                                                          Discovery!                                                                      295

periodontal diagnosis, and accurately assess risk for periodontal                           for Clinical Research from the American Dental Association. In
disease. Several clinical trials by his group provide a clear                               conversations with several directors of these organizations, we
rationale for the local and systemic beneficial effects of                                  were asked to note that Page has a long and positive history of
surgical, non-surgical, and maintenance periodontal therapy.                                professional service, with an extraordinary ability to bring
Most recently, an Oral Health Information Suite was developed                               people together to solve complex administrative as well as
as an Internet tool available in the offices of all dental                                  scientific problems.
practitioners to assess risk for periodontal diseases, dental                                   We join Roy's many friends and colleagues in observing
caries, and oral cancer. The assessment tool provides a risk                                that while he is inherently shy, gentle of voice, and intensely
score, textual diagnosis, and recommended treatment plan and                                private, Dr. Page is most of all a kind, caring, and gentle human
is currently being evaluated nationally and internationally for                             being. He applies extraordinarily high expectations of
its potential to help contain the cost of oral healthcare while                             excellence to himself and those around him, but one could have
significantly improving oral health (Page and Martin, 2007).                                no more steadfast friend. Dr. Roy Page brings great credit to
    Dr. Roy Page's journey of discovery has addressed critical                              the profession, and the authors join the many colleagues who
questions about the biology of the periodontium and disease                                 are far better for his wise counsel, his scientific excellence, and
processes that adversely affect periodontal integrity. Roy would                            his friendship.
have us recognize the efforts of a large number of individuals
who worked with or collaborated with him. He would also                                     REFERENCES
gratefully acknowledge the generous training and research                                   Bordin S, Page RC, Narayanan AS (1984). Heterogeneity of normal human
support provided by the National Institute of Dental and                                        diploid fibroblasts: isolation and characterization of a unique
Craniofacial Research over a period of more than 40 years.                                      phenotype. Science 223:171-173.
Taken collectively, collaborative and multidisciplinary research                            Narayanan AS, Page RC (1976). Biochemical characterization of collagens
guided by Page has clarified the composition of the periodontal                                 synthesized by fibroblasts derived from normal and diseased human
                                                                                                gingiva. J Biol Chem 251:5464-5471.
connective tissue matrix, postulated new paradigms to the
                                                                                            Page RC, Eke P (2007). Case definitions for use in population-based
understanding of periodontal pathogenesis, and fundamentally                                    surveillance of periodontitis. J Periodontol 78(7 Suppl):1387S-1399S.
influenced the diagnosis and clinical management of the                                     Page RC, Kornman KS, editors (1997). Pathogenesis of periodontitis.
periodontal diseases. There will undoubtedly be more to come.                                   Periodontology 2000 14:1-248.
He is the recipient of honors and awards from many                                          Page RC, Martin JA (2007). Quantification of periodontal risk and disease
professional organizations, including the Distinguished                                         severity and extent using the Oral Health Information Suite (OHIS).
Scientist Award from the American Association for Dental                                        Perio - Periodontal Practices Today 4:163-180.
                                                                                            Page RC, Schroeder HE (1976). Pathogenesis of chronic inflammatory
Research, the Basic Science Award in Periodontal Research                                       periodontal disease: a summary of current work. Lab Invest 34:235-
from the International Association for Dental Research, the                                     249.
Gies Award and a Citation of Merit from the American                                        Page RC, Schroeder HE (1982). Periodontitis in man and other animals.
Academy of Periodontology, and the Norton M. Ross Award                                         Basel: S. Karger, pp. 1-330.

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                                                           International and American Associations for Dental Research