The Legacy of Dental Research
Allison M. DiMatteo, BA, MPS
In the past 60 years alone, the research and discoveries within the discipline of dentistry—as well as from other fields that have been applied to it—have led to dramatic changes and paradigm shifts in terms of professional practice. Dentistry can credit such initiatives for its ahead-of-the-curve role in health promotion, risk assessment, disease prevention, treatment planning, treatment therapeutics, restorative materials, and predictable clinical outcomes, among other achievements.
“Research is a fancy way of saying curiosity and wonderment and thinking about how to make something better,” believes Harold Slavkin, DDS, dean of the University of Southern California School of Dentistry and the former director of the National Institute of Dental and Craniofacial Research (NIDCR). “Ideas come from people, sometimes in a discussion in a clinical setting; sometimes from students, faculty, and staff; they definitely come from practicing dentists all over the world; and they also come from fields outside of dentistry.”
There is a certain amount of serendipity in research. However, more often than not, the discoveries that have changed the dental profession come from prepared minds that understand what is being studied and see its application to dentistry.
“Scientists—whether in academic institutions, industry, or private practice—will understand the problems general dentists or specialists are facing on a day-to-day basis and develop approaches for how they can be solved, or how treatments can be developed to alleviate diseases or conditions,” explains Christopher Fox, DMD, DMSc, the executive director of the International and American Associations for Dental Research (IADR/AADR). “Dental research is really the scientific underpinning of the entire profession, and it is really what makes dentistry a profession and not just a trade.”
Basically, everything that a practitioner does is dependent upon scientific research and biomedical research in general, stresses Dominick DePaola, DDS, PhD, president and chief executive officer of The Forsyth Institute. Because the oral environment is part of the human biologic system that changes every day, clinicians must understand the biology of the individual as they apply any kind of diagnostic for treatments or preventatives. The common denominator is research, he says.
As a testament to the richness of the discipline’s research history, crediting everyone and everything that has contributed to the current state-of-the-art of dentistry is an overwhelmingly daunting task. However, the attempt to do so provides a simultaneously reflective, thought-provoking, and inspiring glimpse of what could be in store for the profession. And dentistry is, now more than ever, a profession that is truly at the recognizable forefront of promoting oral health, assessing systemic health, and pioneering new approaches to both diagnostics and restorative and regenerative treatments.
Here’s the Inside look at what some believe has rocketed dentistry to increasingly new heights of innovation and patient care, as well as what’s been required to make it all possible. With past achievements serving as a solid foundation on which to build new knowledge, the legacy of dental research promises a future brimming with opportunities and exciting possibilities.
We Are Where We Are Now Because...
We understand bacteria and infection. Louis Pasteur established microbiology and the postulates of infection and immunity in the late 1890s. Jumping ahead, Slavkin notes that the discoveries of oral biology—which later went from science to infection control—at the beginning of the 20th century, as well as the fact that nutrition is linked to health promotion (eg, a lack of Vitamin C causes scurvy and influences gingival health), were also significant to dentistry.
“It’s an ongoing process, but understanding microbiology as it relates to dental caries and periodontal disease—and the fact that both of them are really infectious diseases—has changed the way we treat both of those conditions,” says Fox.
The recognition that caries and periodontal diseases are infectious has enabled dentistry to develop strategies of prevention, of which Lawrence Tabak, DDS, PhD, the current and seventh director of the NIDCR, believes that members of the profession should be very proud. In many ways, dentistry has been ahead of the curve relative to medicine in general when it comes to prevention.
“I think dentistry has emphasized prevention for so many years,” Tabak believes. “Certainly the establishment of bacterium in the caries and periodontal disease processes is part of that.”
We have general and local anesthesia. In 1905, Alfred Einhorn, a German chemist, developed a local anesthetic later marketed under the name Novocain.1 However, even before that, in 1844, Horace Wells, a dentist from Connecticut, discovered that nitrous oxide could be used as an anesthesia and successfully used it to conduct several extractions in his private practice.1
“General and local anesthesia have really been dentistry’s discovery,” believes Fox. “It’s also been dentistry’s gift to medicine as well.”
Standards have been set. Greene Vardiman Black, a leading reformer and educator of American dentistry, published Operative Dentistry in 1908.1 Black also developed techniques for filling teeth, standardized operative procedures and instrumentation, developed an improved amalgam, and pioneered the use of visual aids for teaching dentistry.1
Additionally, notes Slavkin, the Geis Report, sponsored by the Carnegie Foundation, advanced modern university-based dental education in the United States and Western Europe in 1926. Later, in 1995, the Institute of Medicine published Dental Education at the Crossroads, a major call for reform in dental education and the practice of dentistry, he points out.
Federal funding for dental research was established. President Harry S. Truman signed a Congressional bill to formally establish the National Institute of Dental Research in 1948, which initiated federal funding for dental research.1 The organization changed its name in 1998 to the National Institute of Dental and Craniofacial Research (NIDCR), and its mission continues today to be the improvement of oral, dental, and craniofacial health through research, research training, and the dissemination of health information. “This was the beginning of the infusion of science, technology, and public money into university-based research,” Slavkin says.
The benefits of fluoride were discovered. Between 1930 and 1940, the beneficial effects of fluoride were discovered by Frederick S. McKay, a dentist from Colorado who was convinced that brown stains on his patients’ teeth were related to their water supplies. His research verified that drinking water with high levels of naturally occurring fluoride was associated with low dental caries, but a high degree of mottled enamel.1
In the 1940s, clinical trials were invented, with one of the first being conducted on the fluoridation of drinking water. H. Trendley Dean, the first NIDR director, determined the ideal level of fluoride in drinking water to substantially reduce decay without mottling.1
“This established the most significant public health measure of the 20th century—water fluoridation to reduce tooth decay,” explains Slavkin. The water fluoridation era began in 1945, when Newburgh, New York, and Grand Rapids, Michigan, began adding sodium fluoride to their public water systems.1 Subsequently, a whole range of fluoride products that could be used by the public—including dentifrices—were researched, developed, and introduced.
According to Tabak, all of the research that went into establishing fluoride as a means of preventing tooth decay was essential to today’s dentistry and led to the use of fluoride in other forms, including gels, rinses, dentifrices, and sealants. Fluoride for the prevention of tooth decay was named as one of the top 10 public health advances of the 20th century by the Centers for Disease Control and Prevention, he says.
Adhesive bonding and polymer chemistry were developed. In 1949, Oskar Haggar, a Swiss chemist, developed the first system of bonding acrylic resin to dentin.1 Later, in 1955, Michael Buonocore described the acid-etch technique, a simple method to increase the adhesion of acrylic fillings to enamel.1 With the advent of polymer chemistry, Rafael Bowen developed Bis-GMA in 1962. This thermoset resin complex continues to be used in most modern composite resin restorative materials.1
“The first prototype dental sealants done by Bowen in the early 1960s were the prerequisite to establishing composites resins,” explains Slavkin. “Obviously today dentists use composite resin, and the public enjoys and benefits from these very much, and it all goes back to the original polymer chemistry.”
High-speed rotary instrumentation was invented. John Borden introduced a high-speed, air-driven, contra-angle handpiece in 1957. The Airotor obtained speeds up to 300,000 RPM and was an immediate commercial success, paving the way for a new era of high-speed dentistry.1
“The end effect of treatments of the dental caries process has been greatly enhanced by high-speed handpieces compared to what was available before,” notes Fox. “Combined with local anesthesia, high-speed handpieces make dentistry kind of painless.”
Implant dentistry was introduced. The first Vitallium dental screw implant was inserted in 1937 by Alvin Strock.1 The Vitallium material—the first successful biocompatible implant metal—was developed the previous year by Charles Venable, an orthopedic surgeon.1 Much later, in 1965, Professor P.I. Brånemark placed the first Brånemark dental implant, representing the first practical application of his discovery of osseointegration.2
“Implants have enabled dentists to restore function in a different and simple way using biological approaches and very specialized materials,” explains DePaola.
Host response to infection and inflammation is better understood. According to Fox, dentistry’s increasing understanding of the host response to inflammation, as well as how the body reacts to microbiota in the oral cavity, has been important to an overall understanding of the disease process and how to treat it.
The digital revolution occurred. Lumped into the past 20 years or so are other innovations that have dramatically—and rapidly—changed the way dentists manage and practice dentistry. All of it, Slavkin says, is the result of digital technology: computers and telephones, digital radiography, CAD/CAM chairside restorations, intraoral imaging, computerized patient records, and practice management software. Additionally, high-tech products—such as high-intensity curing lights, caries diagnostic tools based on laser evaluations, and others—continue to change dentistry at a rapid pace.
The link between oral and systemic disease is now recognized. In 2000, the US Surgeon General released Oral Health in America, the first such report in the history of the United States to talk about the strengths and weaknesses of dentistry in this country, Slavkin says. With it came the understanding that without oral health, no person is truly healthy.
What’s more, notes Tabak, the wealth of research pointing to associations between oral disease and systemic diseases—such as cardiovascular disease; delivery of preterm, low-birth-weight babies; diabetes; and others—is giving “scientific credibility to that fact, and now both the public and the broader medical community are beginning to embrace this.” This, he says, is significant because it catalyzes dentists to work more closely with their colleagues in medicine, nursing, and pharmacy as an integral part of the biomedical team.
“I think what our medical colleagues have come away with is an understanding that dentistry has a great deal to offer the health care enterprise as a whole, that we are surely equal partners in this,” Tabak observes. “I think this is due in large part to the research that has helped identify these oral–systemic relationships.”
Where We’ll Be In The Future
Based on the research that’s taking place today, change is in the air within the next 10 to 20 years, if not sooner. According to Tabak, a whole new set of tools will be available to identify individuals with the greatest risk for the variety of oral diseases and conditions that the profession now faces. Such innovative diagnostics will result from genome association studies and the identification of relevant biomarkers found in saliva.
And saliva is, without question, a subject of widespread research interest—and one which holds the potential to impact dentistry’s future position in the overall health care arena. According to Slavkin, the “rediscovery” of saliva as a diagnostic fluid represents exciting possibilities. He foresees saliva and new technologies from the digital revolution converging at some point (See Fast Forward, this page).
“Although it’s further into the future, identifying biomarkers will allow us to create interventions that are personalized for an individual,” Tabak explains. He elaborates that it is understood that not everybody metabolizes medicine in exactly the same way. If dentists can predict early on that a particular individual will need a particular medicine, they will be able to personalize the level of the medication to best match the individual’s makeup and his or her ability to metabolize it.
What’s more, the manner in which caries and periodontal diseases are treated will be dramatically different than it is today, he predicts. Today, he says, the emphasis is on prevention, but still with a focus on restoration of form and function.
“In the future, because we will have the wherewithal to identify people who are most susceptible—as well as the earliest stages of diseases—interventions will allow for remineralization and a reversal of the disease process,” Tabak notes. “In the case of periodontal disease, we’ll be able to alter the bacterium present to a more healthy bacteria group, and for oral cancer, identification at such an early stage would enable us to institute therapies that would help reverse the progression so it never proceeds beyond that point.”
Overall, Tabak says, dentistry will have a whole new arsenal of opportunities and abilities to tackle devastating diseases and conditions that require restoration, as well as diagnostic and preventive measures. Between stem cells and tissue engineering, as well as gene therapy, dentists will be able to achieve what was previously impossible, he says.
In this regard, Gerard Kugel, DMD, MS, PhD, associate dean for research at Tufts University School of Dental Medicine, sees the real future—and the real breakthroughs—coming from tissue and biomedical engineering research, including stem cell research. At Tufts, researchers are exploring ways to grow bone on a matrix such that it may be possible to grow bone to replace that which is lost both periodontally and post-surgically. Additionally, scientists there are growing primitive teeth from stem cells, suggesting that, someday, clinicians could be replacing missing teeth by regrowing them.
“This is research that might not be implemented in practice for another 20 or 30 years, but its beginnings are happening now,” Kugel asserts. “It’s not make-believe.”
DePaola sees the future of dentistry moving from a surgical model of care, where instrumentation is required for the detection and treatment of disease, to a more medical model, where biologics are the mainstay. Dentistry of tomorrow will embrace the ability to restore form and function to parts of the oral cavity and craniofacial complex that have been damaged by either pathology or trauma using the regeneration techniques being studied right now, he says.
If you’re a dentist, dental hygienist, or specialist, then your image, your reputation, and your stature among other professionals is affected by whether or not you’re from a university-based education program or a trade school. Research in all its forms—government-sponsored, academic, independent, product development—supports the intellectual underpinning of the dental profession as a whole.
And the legacy of dental research is something to be proud of, as well as to look forward to, as it shapes and changes the face of the profession moving forward, Tabak asserts. As a result of the research that has and continues to take place, dentists have a much fuller understanding of the biologic basis of a variety of diseases and conditions. This, he says, is catalyzing a move of dentistry away from mechanical toward biomedical management of disease. Simultaneously, dentistry’s importance to health care overall is gaining greater significance.
“We are greatly enhancing our ability to detect disease at an earlier state of progression,” Tabak says. “As a result, the type of intervention that we are going to be able to use is going to be very different than what the profession has traditionally used.”
From Kugel’s vantage point, he sees a lot of things happening in dentistry that practicing clinicians don’t because they’re involved in day-to-day treatments. Currently, dentistry involves determining the best crown or cement to use, and that’s today’s reality, he says.
“Today, we may be talking about what materials to use to build up a broken-down tooth,” Kugel says. “Tomorrow, you may be talking about how to regrow enamel and dentin on that broken-down tooth.”
Perspectives on How & Why Dental Research Has Changed Dental Practice
To feel the impact that science and technology have made on what we do and how we think, as well as how we’re already—maybe even subconsciously—changing the way we do things now, it’s worth taking a look at the way things were in years gone by. Doing so provides cascading “Gee,” “Hmm,” “Why didn’t they think of that sooner?” and “Yes, I see how that made sense” reflections. It also drives home the realization that evolution within the dental profession is ongoing and continuous. The greatest and most thorough knowledge and understanding within dentistry is yet to come.
“The legacy of dental research is that it reviews the past, modifies the present, and creates the future,” explains Tony Volpe, DDS, MS, the vice president of clinical dental research and scientific affairs for Colgate-Palmolive Company and a clinical professor of periodontics at the University of Medicine and Dentistry of New Jersey Dental School. “Research is the cornerstone of progress not only for the practice of dentistry, but also pretty much all endeavors in life.”
RETENTION, PREVENTION, AND PATH OF LEAST INVASION
Once upon a time, when someone had cavities or otherwise diseased and decaying teeth, they were extracted—no questions asked. After all, centuries ago teeth with cavities were akin to limbs with gangrene. They had to be amputated, explains Tony Winston, a research fellow from Church & Dwight.
Then, in the 1800s, the idea of removing only the diseased portion of the tooth and filling it in was developed. The original material was lead, which soon gave way to mercury amalgam, Winston notes. Since then, the resilient amalgam material has been the mainstay of surgical dental treatments.
“Amalgam really was an amazing breakthrough,” Winston says. “In the future, emerging materials and techniques will allow you to detect early signs of a carious lesion in a tooth and then, instead of actually drilling and filling—which is damaging to the tooth—use therapeutic medications to reverse the disease and stop it.”
With fluoridated water and fluoride toothpastes in the 1950s and 1960s, the era of preventive dentistry began, leading subsequently to topical fluoride solutions, gels, and varnishes. The focus on the prevention of dental disease—not just the treatment of it—also led to increased interest in oral health education in hopes that preventive measures would have a positive impact on children’s oral health.
“This is very significant,” Volpe says. “Prevention wasn’t something that was done before, but then it became important to the profession.”
It became important to the public, also. The introduction and later widespread use of toothpastes containing fluoride demonstrated that teeth could be retained caries-free for years.
But that wasn’t always the case. Looking back to the 1950s and 1960s, by the time a patient reached the age of 75 or so, they’d had teeth extracted and dentures fitted, Volpe notes. Also, full-mouth fixed prosthetics were once acceptable. But, such restorative treatments were shown to produce less than ideal occlusion, as well as result in difficulties in trying to repair or modify these appliances, Volpe explains. As a result, things changed.
Research also contributed to changes in the manner in which periodontal therapies are performed. Until recently, there were basically two modalities to treating periodontal disease, Winston explains. One was root planing and scaling, which, if performed correctly, would require several hours spanning several office visits, with the clinician working quadrant by quadrant. The other was gum flap surgery, an invasive procedure that, very often, didn’t stop the progression of the disease, he says.
But when research demonstrated that periodontal disease progresses in certain patterns—not necessarily affecting all teeth or all tissues around teeth—the need for total mouth periodontal surgery was eliminated, Volpe notes.
“Now we selectively deal with periodontal surgery and selectively administer subgingival therapeutic agents,” Volpe says.
With increased and specialized knowledge came dental specialties—periodontics, endodontics, orthodontics, and the like. Volpe notes that these disciplines came into full maturity within the last 30 or 40 years, and their significance in the profession is more widely recognized.
“Individual dentists were doing the best they could, and sometimes referring patients out for more work, but it wasn’t in the organized structure that it is today,” he says. “When specialties became really entrenched, there became educational programs accredited for them, and they have become tremendously important to dentistry.”
With the understanding of bacteria came an understanding of infectious diseases. As a greater understanding of that area was researched and developed, so too was the need for infection control. And necessity, as they say, is the mother of invention.
“If you went to a dentist 30 or 40 years ago, there were no face masks, no gloves, really no central sterilization mechanism, and no disposable instruments,” Volpe recalls from his more than 45 years in dentistry. “Today, we have protection for ourselves as well as the patient. All of this has made a dramatic and significant impact on the way dentistry is practiced today.”
With the introduction of the high-speed handpiece in the 1960s, dentistry was relieved of the pulley system with a push down pedal.
“This was laborious, it was time-consuming and inaccurate, and it wasn’t a pleasant experience for the patient,” Volpe remembers. “When the high-speed handpiece came, it changed all of that. All of a sudden, we were able to create restorations faster, better, and with less discomfort to the patient.”
For this reason, he considers this innovation among dentistry’s absolutely significant breakthroughs. Lawrence Tabak, director of the National Institute of Dental and Craniofacial Research, also points to innovations that have affected patient comfort as important to the profession.
“Before the advent of local anesthesia, as well as before the high-speed handpiece, many folks tell horror stories of how dentistry once was,” Tabak says. “Modern dentistry is relatively painless, and I think most patients now appreciate that.”
But under the category of efficiency came other more recent, high-tech advancements, such as digital radiography, voice-activated recordings and computerization of information, and modern implantology. According to Volpe, all of these have dramatically changed the way dentistry is practiced in the modern era.
The introduction and advent of new dental materials have changed dental practice, Volpe says. Composites that can be used for fillings instead of amalgams, as well as new porcelains for fixed prosthetics, have helped usher in the age of esthetics.
“All of these materials are very esthetic in contrast to the gold and amalgam fillings we used to use,” Volpe observes. “They were fine restorative materials, but they weren’t very esthetic materials.”
But, looking ahead, Volpe predicts that the research taking place today may result in recommendations for how to handle esthetic restorative procedures—including implants—in the future. Current research will help modify the revolutions taking place in esthetics and implants, he says, just as it helped modify the materials and techniques of the past.
“I think research will show us that we have to be more prudent about what we do to teeth to achieve the esthetic effect—whether we etch them, bond to them, or whiten them—because it isn’t always reversible,” Volpe says. “With implantology, it will show that we have to consider the periodontal aspects and the impact on bone and other superstructures, and it will help us understand the condition called peri-implantitis.”
ORAL/SYSTEMIC HEALTH AWARENESS
As research amassed to gain an understanding of periodontal disease and the bacteria that cause it, the increasing knowledge base was a foundation for connecting oral health to overall health. Simultaneously, there have been great leaps forward in the use of antimicrobial and antibiotic treatments to ensure periodontal health, Winston says.
“Attention is being paid to the connection between oral disease and systemic health,” Volpe points out. “In other words, the mouth could be a source of infection for the rest of the body; it could be linked to a certain extent to diabetes or other things of this nature, for example. The fact that people are talking about this link is changing the dynamics of dental practice.”
From Questions to Answers and then to Application, It Takes a Lot to Make Research Real
What makes today’s groundbreaking research possible is a product of perception and position within the dental profession at large, if not the research community itself. Some of the best ideas for what to study and what research to conduct come at the interface between different ways of thinking, believes Harold Slavkin, DDS, dean of the University of Southern California School of Dentistry. And people, first and foremost, are at the heart of those interfaces.
“From the synthesis of ideas from chemists, biologists, dentists, and others, a new idea is born and a new way of thinking is developed,” he explains. “The most impressive breakthroughs in any areas of humanity come at the interface between different ways of thinking.”
The Power of People
According to Slavkin, to make meaningful dental research possible, there must first be a perceived value. “Among all of us who are in the dental profession, there needs to be a personal and professional value of science and technology,” Slavkin says. “If we do not value and utilize innovations, discoveries, best practices, and evidence-based patient care, our future will not look very good.”
Perceived value of science and technology can then translate to support for research endeavors through local universities, organized dentistry, and dental manufacturers, as well as funding by the federal government.
Secondly, there must be advocacy for improvement throughout the profession. When members of the profession are only interested in the status quo, there is no need for research, Slavkin says. “In fields where people become complacent, research dries up, so advocacy for improvement must be a prerequisite for dental research,” he explains.
Third, an emphasis must be placed on the cost-benefit relationship of the research to dental practice and/or patient health. In some circles, this emphasis is realized through translational research, that which can show a direct link between what is being studied and how it will be applied in day-to-day practice.
Finally, positive attitudes and appreciation for research must be fostered in dental school education programs so that faculty, staff, and students can become engaged in the process, Slavkin says. This point in particular lends itself to the number one criteria for enabling dental research on Christopher Fox’s list: people.
“You need a pipeline of researchers,” says Fox, DMD, DMSc, executive director of the International and American Associations for Dental Research (IADR/ AADR). “That means encouraging students to pursue academic and dental research careers.”
Dominick DePaola, DDS, PhD, president and chief executive officer of The Forsyth Institute, agrees. In his opinion, it is critical to begin engaging students in research early on, while making it clear when they graduate that they shouldn’t leave research behind. Rather, graduating dental students should carry with them their ability to be critical thinkers capable of evaluating the literature and new technologies and making informed decisions about what might be in the best interests of patients and their practices alike, he suggests.
Facilities & Funding
Fox also indicates that there needs to be an infrastructure in which to conduct the research—laboratories, facilities, buildings, equipment, etc. Where the research is conducted could range anywhere from biomedical institutions to dental schools, and from health science centers across the nation to private practices, notes DePaola.
“The kind of institution that you work in will determine how research ideas are nurtured and ultimately cultivated,” DePaola says.
And every research institution—and initiative—requires funding.
“We are never going to have as much funding as we have research questions,” Fox observes. “So the research questions must be prioritized.”
“The development of any idea into a really serious research enterprise requires significant funding, and the funding has to come from a variety of sources,” DePaola stresses. “These include the NSF, NIH, and NIDCR, but certainly they’re not the only sources. The dental industry has been a big source of funds, as well as philanthropy, other non-dental corporations, and Big Pharma.”
Fox encourages dentists to stay abreast of what is taking place in the dental research community and support research funding by being involved in the political process. The latter, he says, requires a conscious effort to ensure that their Congressional representation really knows about the importance of dental research.
“If I were to add up the amount of money that the American people have given to the NIDCR since 1948, it is much less than a billion dollars,” explains Slavkin. “On the other hand, when I look at the benefits of the research—the health and quality of life that have resulted directly from that institute—there is a national savings of $4 billion per year.”
Compared to the $2 trillion dollars that Americans spend on health care, the investment made into the NIH is roughly 5%, and into the NIDCR, even less—close to one eighth of a percent. “So, in terms of thinking about return on investment, one of the best investments that any of us can make is in dental research and technology,” Slavkin asserts.
Peer Review & Information Transfer
Once research has been completed and the questions are answered, the knowledge gained from experimentation and observation must undergo a peer review, Fox emphasizes. This can be accomplished through various publications and dental meetings, including those sponsored by the IADR/AADR.
Finally, information transfer is necessary to translate the research into chairside application, he says. To this end, the IADR—established in 1920 as a non-profit organization that currently has more than 11,000 active individual members worldwide—facilitates the communication and application of research findings.1 Similarly, the AADR—the US division of the IADR that currently has more than 5,000 individual members and 100 institutional members within the US—endeavors to increase opportunities for scientific exchange and enhance science transfer to scientific and professional societies, educators, clinicians, and the public.2
Lawrence Tabak, DDS, PhD, the current and seventh director of the NIDCR, says that as dental practice becomes increasingly evidence-based, general dentists should continue to expose themselves to the latest research findings. Doing so will enable them to remain in a position where they can provide the very best treatment for each of their patients.
But, as DePaola points out, it takes an average of 15 or more years for what is studied to develop from its early stages of discovery to translation into practice. Ultimately, translation is really affected through the education of dental students and practitioners, during which they are shown that new technologies and techniques will benefit patient care, he says.
“Dentists, in many ways, have been selective adopters of new technology, and some of the biological approaches to dental medicine have been slow to be incorporated into day-to-day practice,” DePaola admits. “When you can demonstrate an economic incentive that allows the research to be applied to daily practice, then it will be applied and utilized quicker than something that is more esoteric.”
According to Tabak, the translation of research into everyday practice is a challenge not only for dentistry but for all medical research. Information transfer to professionals and the public—through literature, association meetings, and the NIDCR’s Web site—is key to ensuring the ready adoption of innovative treatments, techniques, and preventive measures.
Gerard Kugel, DMD, MS, PhD, the associate dean for research at Tufts University School of Dental Medicine, credits the NIDCR with making a concerted effort to communicate with practicing dentists about the research that is taking place and how it stands to benefit the profession. This is important, he says, because government funding for research efforts is ultimately dependent upon the lobbying efforts put forth by constituents who can convince legislators of the value of dental research.
To facilitate the translation and communication process, the NIDCR recently embarked on an ambitious experiment by launching a series of Practice-Based Research Networks. Three 7-year grants, totaling $75 million, were awarded in March 2005 to establish these networks, each of which will investigate with greater scientific rigor everyday issues in the delivery of oral health care.3 The impetus behind the networks is the frequent lack of research data to guide treatment decisions in the dentist’s office.3
The Practice-Based Research Networks that were established are Practitioners Engaged in Applied Research and Learning (PEARL) Network, which is administered by the New York University College of Dentistry; the Dental Practice-Based Research Network (PBRN), administered by the University of Alabama at Birmingham; and the Northwest PRECEDENT, administered by the University of Washington.3 Each regional network will conduct approximately 15 to 20 short-term clinical studies over 7 years, comparing the benefits of different dental procedures, dental materials, and prevention strategies under a range of patient and clinical conditions.3 The networks will also perform anonymous chart reviews—as permitted by the Health Insurance Portability and Accountability Act (HIPPA)—to generate data on disease, treatment trends, and the prevalence of less common oral conditions.3
“There are several hundred practices throughout the country that are now linked together that will be used to address specific research questions that would be best answered in a real world environment, in actual dental practices around the country,” Tabak explains. “An ancillary opportunity here is to determine if research conducted in a practice environment will be more readily adopted by a practitioner.”
A New ADA Initiative
A tell-tale sign regarding whether or not this type of research—at least when it is product focused—is beneficial to practitioners may come when the ADA officially introduces its new ADA Professional Product Report (PPR). Established last year by the ADA’s Council on Scientific Affairs, the PPR is intended to provide ADA members with comprehensive dental product information that is scientifically sound, clinically relevant, and unbiased.4
The PPR will offer ADA members quarterly reviews of products in three dental categories. These products will be evaluated by ADA member dentists who volunteer to join the ADA Clinical Evaluator Panel and offer a few hours each month to provide the Council with their feedback on the products they’ve evaluated in terms of how they actually perform in clinical practice.5 As of February of this year, approximately 850 ADA members had joined the ADA Clinical Evaluator Panel.4
“This is a very important form of research,” explains Kugel. “This type of ‘consumer’ evaluation of products that clinicians may want to use in their practices is immediately relevant because it’s research information that they’re going to put to use right away.”
4 Garvin J. Professional Product Review offers ‘sneak peak’ in ADA News. February 20, 2006. www.ada.org/prof/resources/pubs/adanews
5 Crozier S. Making informed choices. New publication spotlights clinical input from dentists, ADA laboratories; offers buyer's checklist. August 23, 2005. www.ada.org/prof/resources/pubs/adanews
Manufacturers: The Other Supporters & Scientists in Dental Research
When considering the landmark achievements that dental research has made possible within the profession, the contributions from the industrial—or manufacturing—side of the profession cannot be overlooked. Like the more “puritan” biological-based discoveries, research developments and product innovations from manufacturers have changed the practice of dentistry throughout the years.
Product developments, for example, have enabled treatments that are not only functional but also esthetic. Additionally, whereas aggressive removal of tooth structure to accommodate restoration placement was once the norm, modern materials resulting from manufacturer developments enable more conservative treatment approaches. Innovations in implants and the interfaces surrounding the tissues, as well as the abutments, have significantly improved the predictability and acceptance of this treatment modality. Products, equipment, and materials have been introduced to clinicians and laboratories to increase efficiency without sacrificing efficacy.
“Every new concept or new product comes from research, and the thing to remember about research is that it is conducted by individuals in their office environments, researchers and clinicians at dental schools and specialized research institutes, and last but not least, by the dental product manufacturers themselves,” explains Tony Volpe, DDS, MS, vice president of scientific affairs for the Colgate-Palmolive Company. “Although concepts may come from other sources, it’s a general rule that product development research and following through to an actual finished product and application is conducted by industry.”
According to Andrew Lichkus, PhD, chief technology officer for DENTSPLY, the legacy of dental research—including that which has been conducted by dental product manufacturers—is the significant number of researchers from several disciplines dedicated to improving the standard of care through the clinical interface of the dental profession. Their efforts provide products that enhance care when placed in the hands of dental professionals, whether the application is the diagnosis, prevention, or treatment of disease.
“There are tremendous scientists that work for industry,” remarks Christopher Fox, DMD, DMSc, executive director of the International and American Associations for Dental Research (IADR/AADR). “Dentists should view the science that is happening in the dental industry as just as important as the research taking place at academic institutions.”
From Concept to Patient Care
Like the wonderment that launches traditional scientific investigations, the ideas that ignite product research and development come from a variety of sources. Some are internal to the company, others external. They come from members of the dental profession, based on an understanding of day-to-day practice needs and the direction in which dentistry is heading. There may be seminars, focus groups, or market research studies that provide input to the product development process.
“Some ideas come from academia, individual inventors clearly have a role, and now—more prominently—start up biotechnology companies may do initial proof of concept research,” explains Robert Gerlach, DDS, MPH, principal scientist in worldwide clinical investigations for Procter & Gamble. “Those groups may partner with larger organizations for further development, and some ideas may also come from policy making, regulatory issues, or even emerging health awareness.”
Lichkus sees manufacturer efforts as the translation mechanism for the commercialization of internal (company) and external ideas from clinical professionals, the scientific and engineering community, or other researchers outside of dentistry that could potentially improve dental treatment outcomes. There are potentially numerous technologies and innovations outside the dental industry, he emphasizes, that can also play a role in solving dental problems.
“Industry has recognized over the years that basic research—without some clearly defined profitable goal—is risky and expensive,” explains Tony Winston, a research fellow with Church & Dwight. “Industry is only profitable if it has a product to sell, and academic knowledge has its greatest value when it is applied to solving problems in the public domain. So, companies tend to support basic research done by universities or other non-profit organizations in areas of their interest.”
Manufacturers develop concepts that they need to know are valid and can be applied to the general market, a need that Ed Shellard, DMD, president of Kerr Corporation, believes motivates dental manufacturing to support research at the university or non-profit level. There is general agreement, he says, that there needs to be a collaborative effort between university-based or government-supported research centers and manufacturing.
“Developing a product today is a very complex process that requires several years, from idea conceptualization to creation of prototype products, as well as the upscaling process and validation studies,” explains George Tysowsky, MPH, DDS, vice president of technology for Ivoclar Vivadent, Inc. “These sequential undertakings require significant efforts by chemists and engineers throughout the product development process, followed by conscientious studies by in-house and/or independent researchers to validate the efficacy of the final products.”
And the efforts are significant. Volpe explains that within the manufacturing environment, there are people who devote themselves to developing basic concepts and testing those early concepts, as well as others who secure feedback on those concepts from users. From there, the basic research is conducted that leads to product development and the creation of prototype models, after which patents are filed and funding is secured to enable the completion of other necessary processes. Those include safety and efficacy testing, regulatory and professional agency approval, and a host of other activities that all lead to product delivery.
“Industry plays a vital role in all aspects of research to develop products that enhance the practice of dentistry,” Volpe asserts.
The reliable manufacturers involved in establishing testing protocols choose to do so to ensure that those products are successful and can perform up to the expectations of the final clinical environment, Tysowsky explains. The clinical trials or laboratory studies that are required are very comprehensive.
Because government funding has, in recent years, focused more on infrastructure development in dental schools and basic science, research application has often been left to manufacturers, Gerlach explains. In this regard, randomized clinical trials represent the highest form of evidence of safety and efficacy, he says, and these usually occur late in the research and development process, after the bench research has been completed.
“This is high-risk, high-reward research that is often sponsored by industry, often in collaboration with various research organizations,” Gerlach says. “The research is extensive and highly regulated, and it results in the evidence that we, in dentistry, have come to embrace or reject depending upon what it shows with respect to new techniques, methods, materials, or products.”
Collaboration & Funding
“Quality research is very costly,” Tysowsky emphasizes. “There are multiple millions of dollars involved, obviously from the funding of research staff, in-house testing, external in vitro testing, and also clinical trials. Much of that burden does rest on the manufacturers.”
Although some support may be received through government agencies such as the National Institute of Dental and Craniofacial Research (NIDCR), oftentimes the burden of funding research related to specific product developments rests with the manufacturers, Tysowsky says. But manufacturers can’t do it all alone, and outside research and validation is key to ensuring successful clinical outcomes. It’s a two-way street.
“Truly translating university-based research findings into applications for day-to-day practice requires commercialization,” Shellard says. “Without collaboration among manufacturers, universities, and clinicians, that research—and its resulting products—wouldn’t otherwise get to into the hands of clinicians or benefit the public.”
Within the manufacturing world itself, the funding issues companies face are not unlike those of universities or government-supported centers. There is competition for money to support the research of a novel idea. However, in addition to the basic research, manufacturers are faced with the burden of proving two additional requirements, Gerlach explains. First, the company must demonstrate that it can obtain a proprietary or patent position. Second, it must show that the idea has the potential to eventually be profitable.
Overall, like the research taking place in academic environments, manufacturer research also involves selective resource allocation, but across the entire product development process of idea generation, concept formation, prototype development, and validation, including clinical studies, Lichkus says. To routinely introduce products which meet the current and future needs of dental professionals, he notes that collaboration between a broad spectrum of clinicians, scientists, engineers, and marketing professionals is required in a successful and innovative product pipeline.
“Creativity and perseverance are also critical characteristics of successful research, and these effectively intangible resources must be stimulated and harnessed as well,” Lichkus believes. “So, if I were to look at research overall, I would say that we allocate significant resources, time, and effort to identify technologies and develop effective, innovative, reliable, and safe products which adequately address the needs of dental professionals.”
Partnering for Tomorrow’s Potential
Like their university and research institution counterparts, members of industry are exerting significant efforts toward the development of salivary diagnostics, enhanced caries detection devices, and methods for assessing systemic disease. According to some, the era of single-tooth treatment is gone, and manufacturers are challenged to support clinicians as the profession moves into a future that encompasses comprehensive care.
To satisfy current and future expectations, dental manufacturers are looking for partners at universities and research centers for testing and validation as they drive new technologies and new areas of developments. Like the profession as a whole, manufacturers are hopeful that eager and interested people will pursue dental research in order to maintain a standard of excellence for the future.
Fast Forward— Tomorrow’s Dentistry Will Be Based on Today’s Research Agenda
Presently contributing to the future is the Human Genome Project (HGP), a 13-year undertaking completed in 2003 that was coordinated by the US Department of Energy and the National Institutes of Health (NIH) at a cost of approximately $3 billion from start to finish.1 Its goals included identifying all of the approximately 20,000 to 25,000 genes in human DNA and determining the sequences of 3 billion chemical base pairs that make up human DNA. Because genes carry information for making all proteins required by organisms—proteins that determine how well an organism can fight infection, among other things—insight into DNA variations has implications for health care, including dentistry, in terms of diagnosing and treating a variety of disorders.2
What does this mean for dentistry? Consider that any biomarker that can be found in blood can also be found in saliva. They’ve always been there, explains Christopher Fox, DMD, DMSc, executive director of the IADR/AADR, but until recently, the tools weren’t available to detect the very small amounts that are present in saliva.
“There is very exciting research taking place at UCLA looking at seven biomarkers for oral cancer,” Fox elaborates. “A methodology has been developed to isolate these biomarkers, as well as a diagnostic test with very high sensitivity and specificity for oral cancers, so this is going to be a very positive step toward early diagnosis and treatment of a devastating condition.”
According to Lawrence Tabak, DDS, PhD, director of the National Institute of Dental and Craniofacial Research (NIDCR), the Institute is constantly looking for opportunities to borrow, enhance, and integrate knowledge from biomedical and technological research. It’s amazing, he says, how creative people can develop implications for dentistry from seemingly unrelated research findings.
“For a number of years, bioengineers have been miniaturizing labs on a chip,” he explains. “Bioengineers, working with oral biologists, quickly realized that a lab on a chip can be adapted for use in the oral environment, and from that was born the salivary diagnostics program that the NIDCR sponsors.”
That program includes the work of dentist/scientist Dr. David Wong from the UCLA School of Dentistry. With support from two, four-year awards from the NIDCR, Wong is establishing the UCLA Collaborative Oral Fluid Diagnostic Research Center and the Human Salivary Proteome Project (www.hspp.ucla.edu). Through the Oral Fluid Diagnostic Research Center, Wong is developing nanotechnology-based microsensors—so called “labs on a chip”—for translational applications for molecular diagnostics of oral cancer and oral pathogens based on saliva.3
“The ability to miniaturize and computerize a variety of hand-held point-of-care devices for measuring wellness, quality of life, disease, and progression of treatment will change the practice of dentistry and medicine in the United States and in the industrial countries of the world,” predicts Harold Slavkin, DDS, dean of the University of Southern California School of Dentistry.
The Human Salivary Proteome Project—also at UCLA—is endeavoring to decipher the entire catalogue of proteins found in human saliva.3 It is one of three groups nationwide that are decoding the entire proteome of saliva, Tabak says. It is proceeding rapidly, and the first draft is expected to be available in the first quarter of 2007.
Combined, the saliva research could lead to the salivary gland being used as a general bioreactor to replace proteins that are missing from an individual. For example, in the case of diabetes, gene therapy could be used to “trick” the salivary gland into producing insulin, Tabak explains. Or, if an individual lacked sufficient growth hormones, the salivary gland could be manipulated into producing what’s needed.
“We are awaiting approval from the FDA to actually begin our human trial for the purpose of using gene transfer in the salivary glands to correct the destruction that occurs during radiation,” Tabak shares. “This is happening real time.”
A Caries Vaccine
Fox also notes that probably within the next 20 years, a caries vaccine will be a reality. “We have the science, so it should certainly be possible to produce a vaccine,” he says. “It’s a matter of getting the right research funding behind it, as well as the right commercial model.”
At The Forsyth Institute in Boston, current research is refining a vaccine that intercepts the accumulation of S mutans on the teeth to prevent decay in animals and delay infection in adults. The Forsyth Institute—one of two organizations worldwide that has placed a major emphasis on developing this type of vaccine for children—is refining this vaccine so that it can be given to children before the bacteria can colonize in their mouths.4
“We have on the horizon the potential for vaccines for dental cavities, which of course would make a monumental difference in preventing dental diseases—particularly caries—in populations that don’t have very good access to care,” says Dominick DePaola, DDS, PhD, The Forsyth Institute’s president and chief executive officer.
Tissue Engineering & Stem Cells
Rather than replacing lost tissue—whether as a result of dental caries or periodontal disease—with artificial materials, tomorrow’s dentistry will focus on getting the body to reproduce those lost tissues, Fox says. Tissue engineering and stem cell research is taking place at a number of different institutions for this purpose. In particular, NIDCR-supported research is currently addressing stem cell biology using cells derived from dental pulp, as well as from bone marrow, as a means to replace lost tooth structure and bone.
“In the next decade or two you will find that stem cells and tissue engineering are going to revolutionize what we currently put under the heading of restoration of form and function,” Tabak says. “I have no doubt that things like pulp capping and restoration of small carious lesions will be augmented by tissue engineering and stem cell-based approaches.”
The Inside Look FROM...
The staff and publishers of Inside Dentistry gratefully acknowledge the time, insight, and thoughtful comments shared by our interviewees, without which this inside look at the legacy of dental research would not have been possible. The following individuals, all well-respected throughout the dental research arena and industry at large, made invaluable contributions to this presentation.
Gerard Kugel, DMD, MS, PhD
Harold Slavkin, DDS
Dominick DePaola, DDS, PhD