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"Dental Research into Gear", 1970–1998: A Review of the Scientific Legacy of Joop Arends
1 The Procter and Gamble Company, 8700 Mason Montgomery Road, Mason, OH 45040, USA; Correspondence: * corresponding author, white.dj.1{at}pg.com
Key Words: remineralization • demineralization • fluoride • surface • hydroxyapatite INTRODUCTION Scientists routinely rely upon constant, unchanging factors in their work. Captured by the intensity of our studies, we occasionally assume that our colleagues are also among the constant factors in our world. When Joop Arends died in 1998, a year before an international symposium was to be held in his honor, dental research lost one of its seemingly constant factors. Since the symposium has never taken place, we have written this paper with the aim of providing a perspective to the legacy to Joop Arends the man and his scientific work. We know that this would have been most valued by Arends and are sure that this should be of additional interest to contemporary researchers.
Born in 1934, Arends became a chemistry student at the University of Groningen, receiving his PhD in 1965. Following a brief period at Princeton, Arends returned to Groningen in 1969 as Full Professor and head of the Department of Materia Technica. Arends was a tireless worker, a "capable doer", and keen observer. He had a remarkable intuition about the potential of new discoveries for further research and clinical and industrial applications. Though Arends spent most of his career "home" in Groningen, he defined "global" scientist from the beginning, traveling extensively throughout his career. Arends realized the value of strong collaborations and developed an extensive research network, nurturing his contacts with colleagues. In total, Arends supervised 46 PhD students (Table
Arends received many honors, the first being the Unilever Chemistry Award as a student. Later awards included the ORCA-Rolex Prize (1981), the IADR Research in Dental Caries Award (1989), the Award of the Japanese Society for the Promotion of Science (1992), an honorary Professorship in Nagasaki (1993), and an honorary Doctorate of the University of Göteborg (1995). Arends held leadership positions in Groningen Dental School, IADR, and ORCA. He was supposed to retire in 1999, and the abovementioned international symposium was to be held under the name "Dental research into gear". This title was derived from a wooden sign that used to decorate his office: "Put brain into gear, before mouth is opened." Those who knew him would agree that this admonition provides a snapshot of Arends’ character—he liked to put things "into gear" without too much ado. A citation analysis revealed that Arends authored/co-authored over 350 peer-reviewed publications and had been cited over 3000 times (through 1998). Scientifically, his most productive period was in the mid-1980s, and more than 70 of his papers (over 20%) were the result of international collaborations. Citation analyses of his most-cited work helped us to confirm our colleague’s primary influence in the field and allows us to memorialize some of these here. FROM ABSORBED PHOSPHATE TO A NEW PARADIGM OF FLUORIDE REACTIVITY Arends’ training in solid-state chemistry fostered his early interest in calcium phosphates. He recognized that the understanding of calcium phosphate chemistry was crucial to the development of improved caries prevention. Research contemporaries such as Walter Brown, Ed Moreno, Racquel LeGeros, Ferdinand Driessens, Larry Chow, George Nancollas, and Edward Eanes revealed that the chemistry of apatites was strongly affected by the complex phase behavior of calcium phosphates, the inclusion of impurities in structures, and surface-specific chemistries. Arends’ work with synthetic apatites ranged from single-crystal studies to precipitates from solution. From experiments on the latter, he became interested in the role of adsorbed HPO4 on enamel chemistry (Arends and Davidson, 1975; Arends and Jongebloed, 1977a,b). This was a unique perspective, distinct from considerations of structural carbonate or hydrogen-phosphate within calcium phosphates. In 1984, Dennis Nelson and Arends proposed that an important reservoir of surface-reacted fluoride—providing an ion-exchanging reservoir for fluoride in solution—was "non-specifically adsorbed fluoride (NSAF)" (Arends et al., 1984)—that is, fluoride hydrogen bonded to absorbed HPO4. Their prediction was based upon combined observations of apatite chemistry and practical observations of the clinical effects of fluoridated dentifrices. Though NSAF held promise as a unique and important reservoir for solution fluoride (FL), until the mid-1990s there were no analytical techniques available to test Arends’ hypothesis. The presence of this material was finally confirmed a decade later by solid-state Nuclear Magnetic Resonance techniques (White et al., 1994). Today, NSAF fluoride is a subject of research efforts to maximize the anticaries efficiency of fluoride dentifrices. LEARNING ABOUT CARIES PREVENTION FROM SHARK TEETH? In advance of Arends’ entry into the field, it was well-known that fluoride was effective for caries prevention and that fluorides were highly reactive with calcium phosphates and tooth enamel minerals. The key question for Arends was: How do fluorides really work? He was puzzled by the diversity of fluoride chemistries (e.g., sources, concentrations, reaction products) which were clinically effective. In 1984, at the Dallas AADR, he was introduced to Bjørn Øgaard, at the time a PhD student in the laboratory of Gunnar Rølla in Oslo. Arends was quite interested in the orthodontic banding protocols being developed in Oslo, and offered his services to carry out microradiographic quantitation of de/remineralization for them. During Arends’ frequent visits to Oslo, including Bjørn’s thesis defense, a close collaboration was developed. This resulted in numerous valuable studies on rates and mechanisms of de- and remineralization of enamel and dentin in vivo (Øgaard et al., 1986, 1988a; Arends et al., 1992a,b). During this period, debate also raged on the most ‘beneficial’ forms of fluoride—systemic vs. topical, fluorapatite vs. calcium fluoride, structural vs. free. Gunnar Rølla received a suggestion from an American researcher about studies on the reactivity of shark enamel. Being comprised primarily of fluorapatite, shark enamel might serve as an ideal model substrate for a ‘concept test’ evaluating the mechanism of fluoride contributions to caries. The ‘Oslo team’ jumped at the opportunity. Their in situ studies showed significant mineral loss in shark enamel under cariogenic conditions, proving perhaps once and for all that tooth conversion to fluorapatite was not the ‘holy grail’ of fluoride research (Øgaard et al., 1988c, 1991). ARENDS AND THE THEORETICIAN— THE CHRISTOFFERSEN COLLABORATION Arends’ contributions to fluoride research were much more than ‘concept studies’ or predictions of new forms of fluoride reactivity. They also included efforts to establish a unified mechanism for the caries process. In 1979, a dental research meeting was being held at the Hotel Scandinavia in Copenhagen. Though not enrolled (viz. no payment received), Jørgen Christoffersen managed to infiltrate an afternoon discussion session and get into a ‘heated discussion’ with Arends on the morphological aspects of apatite reactivity. Christoffersen recalls that Joop, though obviously irritated, was quite diplomatic and recommended that further discussions might be better postponed (to complete the meeting). Jørgen recalls being surprised when, several days later, Arends called and invited Christoffersen to give a lecture in Groningen. Thus began a warm personal friendship and productive working relationship that would last a lifetime. In 1982, Arends and Christoffersen traveled together to the Dahlem Conference on Biological Mineralization. As Joop drove through East Germany, Jørgen recalls that the pair discussed in detail their thoughts on the mechanisms of de/remineralization and influences of fluorides and inhibitors. Christoffersen notes that in this single trip, most of the core plans for their later collaborations were developed! They went on to develop landmark physical chemical models describing formation and possible repair of caries lesions in vitro and the influences of fluoride and inhibitor species (Christoffersen and Arends, 1982; Christoffersen et al., 1982, 1984a, Christoffersen et al., b; Arends et al., 1983), a model for repair of subsurface lesions in fluoride-containing solution (Christoffersen et al., 1982), and ultimately a holistic model of the thermodynamic and kinetic events of caries formation and reversal (Arends and Christoffersen 1986, 1990). DELTA-Z? ARENDS DEFINES A SINGLE PARAMETER FOR COMPARISON IN THE CARIES PROCESS One of Arends’ most public contributions to caries research was the definition of ‘Delta-Z’. Though he did not develop microradiography, this practical contribution reveals his skill in simplifying problems, which often led to his uncanny insights. Arends had a unique combination of ‘let’s do it’ enthusiasm and the ‘adequate’ attention to detail of a solid-state physical chemist. Don White used to joke with his industrial colleagues that Arends reminded him of a chemical engineer trapped in a physical chemist’s body. Jaap ten Bosch recalls that, in the ‘70s, microradiography was used in the Utrecht laboratories of Otto Backer Dirks, with Joop acting as a consultant and thesis advisor to Arie Groeneveld and David Purdell-Lewis. Groeneveld became the first to use microradiography in the Netherlands on teeth, with Joop’s guidance (Groeneveld, 1973; Groeneveld et al., 1974, 1978; Groeneveld and Arends, 1975). Meanwhile, back in Groningen, ten Bosch’s technician, Peter Borsboom, suggested that Groningen should also have microradiography capability. Jaap recalls that Borsboom received typical enthusiasm from Joop, Jaap complied, a special camera was made, Wiepko Perdok’s crystallography x-ray tube was used, and so it started. At this point, Joop’s simultaneous collaborations with Procter and Gamble began to include in vitro and in situ studies examining fluoridation processes in early caries and correlations to clinical activity. Given the wealth of data from combined microradiographic scans, we remained frustrated in the development of a single term to more easily (one may question better) define caries protection from remineralization. Joop had Thad Gelhard, a dentist working for his PhD with intra-oral devices, working with the microradiography system. From a simple practical need for comparative testing, the Delta-Z was thus defined (Gelhard and Arends, 1984). Later, Elbert de Josselin de Jong’s thesis, under the direction of Jaap ten Bosch, would completely define a set of quantitative standards for proper execution of transverse microradiography (TMR) (de Josselin de Jong and ten Bosch, 1984, 1985; de Josselin de Jong et al., 1987). Today, Delta-Z is a trademark, Groningen ‘standards’ are established globally for TMR, and de Josselin de Jong’s company, Inspektor Dental Care BV, develops and commercializes analytical, optical, and quantitative laser fluorescence equipment for caries diagnosis and research! BOB TEN CATE: "(ARENDS) CHOICE TO WORK ON REMINERALIZATION WAS OBVIOUSLY A VERY GOOD ONE!" One of Arends’ distinguishing features was the recognition and development of world-class talent. One of his most famous students was Bob ten Cate (currently head of ACTA Amsterdam, winner of the 2003 IADR Research in Dental Caries Award). Ten Cate first joined Arends’ laboratory to work on a MSci thesis investigating fissure sealants. Following this, ten Cate decided against an industrial career opportunity and chose to remain in Arends’ laboratory for his PhD. Ten Cate recalls the pragmatic reasons for his choice: "Joop was a researcher with a big network and a good eye for promising new lines of research. His choice to work on remineralization was obviously a very good one. He gave you lots of freedom in your work...through him you could meet many people in the field which broadened your interests." In the late 1970s, an elegant series of laboratory experiments would help form the basis for the theoretical and practical considerations of remineralization phenomena worldwide, with research providing an empirical reaction order, rate constants, and histological characterization to describe the location and types of remineralization (ten Cate and Arends, 1977, 1978, 1980; Arends and ten Cate, 1981). Ten Cate would later build on this nucleus to develop the novel concept of F protection under pH cycling (ten Cate and Duijsters, 1982) and to further establish the role of low solution fluoride levels on remineralization promotion and demineralization inhibition (ten Cate and Duijsters, 1983a,b; ten Cate, 1990). The collaborations with ten Cate on combined effects of bisphosphonate (surface inhibitor) and fluoride (ten Cate et al., 1981) would serve as the basis for the modeling of caries mechanisms by Arends and Christoffersen and would provide a mechanistic and explanatory basis for the commercialization of tartar control toothpastes—today a multibillion dollar industry. Ten Cate would later continue this research to establish critical understanding on practical elements of fluoride topical reactivity (ten Cate et al., 1985, 1988). HENK BUSSCHER AND ARENDS’ LEGACY TO GRONINGEN: SURFACE PHENOMENA IN ORAL BIOLOGY AND MORE Based on the literature in the 1970s (Glantz, 1969, 1971; Baier, 1982), Arends realized the potential for chemical modification of the enamel surface with regard to control of dental plaque, and the need for more thorough investigation. The arrival of Henk Busscher at Arends’ laboratory in the late 1970s heralded the introduction of this new field of research to the Groningen repertoire, and set the stage for the evolution of Materia Technica into a global center for biomedical engineering research. In preliminary studies, the concept of dispersion and polar components of surface thermodynamics was elaborated (Busscher and Arends, 1981; Busscher et al., 1983), which proved suitable for calculating surface free-energies of high-energy, crystalline surfaces, like apatites and dental enamel (Busscher et al., 1984, 1987). Similarly, in vivo methods were developed that allowed for the assessment of surface thermodynamic features of biological substrates, including tooth enamel (Busscher et al., 1984; Perdok et al., 1989, 1991). Studies confirmed Glantz’ (1969) observations that more hydrophobic surfaces discourage plaque formation (Quirynen et al., 1989), although the effects of topical agents like amine fluoride were influenced by pellicle-conditioning films (de Jong et al., 1984a,b,c). These preliminary observations led to important avenues of later research (Busscher et al., 1995) and continuation of the dental focus of surface chemistry. However, of most importance to Joop was the establishment of Henk Busscher as Arends’ successor in Groningen. CONCLUDING REMARKS Joop Arends changed caries research forever. His research on the fundamental properties of the chemistry of calcium phosphates, oral biological processes of de- and remineralization, and the effects of fluoride advanced the fundamental understanding of the mechanisms of caries formation and prevention. Collaborative research strongly influenced the commercialization of second-generation fluoridated dentifrices (NaF), tartar control dentifrices, restoratives, denture materials, and implants. His explorations into the detailed understanding of de- and remineralization phenomena have provided a solid foundation for the understanding of how current anticaries treatment modalities work and what should be attempted next. Techniques developed in Groningen for the assessment of remineralization and demineralization processes are the standard for cariologists world-wide. At the top of his scientific career in the mid-1980s, Arends’ intuition led him to start a new line of research into oral surface phenomena, which led to the evolution of an entire laboratory and the development of his capable protégé. With Busscher, another 13 PhD students defended their theses under Arends. In 1998, three months after Arends’ death, the University of Groningen formed a new Department of Biomedical Engineering. This research department continues to carry out dental research as part of its broadened mission, under the direction of Dr. Busscher.
ACKNOWLEDGMENTS The authors thank Dr. Anita Verhoeven for carrying out the citation analyses, and Ellen van Drooge and Ina Heidema for checking citations and lists of publications. The authors also thank Dr. Heinz Duschner—whose collaboration with the authors was developed through Arends’ network of research—for his valuable assistance. Received for publication June 18, 2003. Revision received August 19, 2003. Accepted for publication September 8, 2003. REFERENCES
Journal of Dental Research, Vol. 83, No. 2,
93-97 (2004)
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