FY 2008 Congressional Justification

Authorizing Legislation: Section 301 of the Public Health Service Act, as amended.

Budget Authority

DIRECTOR’S OVERVIEW

From the tube of toothpaste in the medicine cabinet to the sophisticated digital x-ray instrument in the dentist’s office, advances in dental care tell a remarkable story of progress and innovation that has vastly improved the lives of the overwhelming majority of Americans.  The most telling measure of this progress involves those who are edentulous (have lost all their teeth).  Fifty years ago, more than 32% of American adults aged 45 and older were edentulous.  Today, dental research has helped cut that rate by more than half, to less than 15%.  As a result, an additional 18.5 million Americans in this age group--more than the population of Florida—are able to reap the functional and esthetic benefits of keeping some or all of their teeth for a lifetime.  

As the Nation’s leading supporter of dental, oral, and craniofacial research, NIDCR helped to support this success through its mission to improve oral, dental and craniofacial health through research, research training, and the dissemination of health information.  The NIDCR is now sowing the seeds of a new crop of scientific advances that one day could number among its finest accomplishments for the American people.  Tooth decay, periodontal disease, chronic dry mouth, oral cancer--all are en route to profound improvements in their diagnosis and/or treatment.  Research on chronic oral and facial pain, bone and cartilage regeneration, salivary diagnostics, and bio-replacement teeth—all continue to yield new secrets and move ever closer to clinical applications that will benefit millions of Americans. 

Yet despite tremendous improvements in the Nation’s oral health over the past decades, the benefits have not been equally shared by millions of low income and underserved Americans.  The poor, underserved minorities, those living in some rural and inner-city areas, frail elderly persons living in institutional settings and people with special health care needs—all these suffer a disproportionate and debilitating amount of oral disease.  Through activities such as its Centers to Eliminate Oral Health Disparities, cutting-edge research on the causes and repair of craniofacial defects and deformities, and genetic engineering to resolve the debilitating effects of radiation therapies and diseases such as Sjögren’s Syndrome, NIDCR stands ready to help bring the benefits of oral health and function to all.

NIDCR’s vibrant strategic planning process includes extensive vetting during plan development and finalization.  The beneficial outcome is that mission-relevant priorities are clearly identified and articulated, and are used to provide guidance and inspiration to the scientific community and our own professional staff.  Our strategic plan creates a framework within which high-quality research addressing important oral health problems can be organized, while providing a rational means of communicating priorities to the extramural community.  Simultaneously, it allows for sufficient scientific freedom that newly emerging areas of discovery are not overlooked, and affords the opportunity for outside experts to weigh in on our current and future directions. 

This FY 2008 Congressional Justification presents how the Institute will continue to plant the seeds of research and harvest the most scientifically mature of these ideas.  But the process is never static.  NIDCR strives to strike a delicate and appropriate balance in its commitment to the basic and clinical sciences.  It does so through its comprehensive planning process that begins with NIDCR Strategic Plan and culminates in development and funding of promising new research initiatives that will round out the existing grant portfolio and bolster areas of emerging scientific opportunity, while leaving room for top quality investigator-initiated research.  This document explains how we will build upon NIDCR’s remarkable successes to create an even brighter and healthier future for all Americans. 

 
2008 JUSTIFICATION BY ACTIVITY DETAIL

Extramural Research

Integrative Biology

An excellent example of integrative biology in action exists in the arena of oral cancer detection.  About 39,000 people develop head and neck cancers each year;  relative survival rates are among the lowest of major cancers. Only one-half the number of persons diagnosed with oral cancer are alive five years after the diagnosis.    The NIDCR’s FY 2008 plans in this program area include continued support of a multifaceted program that will develop and integrate several new technologies and levels of care into a reliable clinical protocol to improve oral cancer detection and survival.  Technologies under development include devices to aid in earlier detection, rapid genotyping of pathology samples to enhance analysis of suspicious lesions removed for biopsy, and integration of screening, diagnosis and treatment.  NIDCR-supported researchers recently achieved initial success using a customized optical device that allows dentists to visualize in a completely new way whether a patient might have a developing oral cancer.  Called a Visually Enhanced Lesion Scope (VELScope™), this simple, hand-held device emits a cone of blue light into the mouth that excites various molecules within our cells, causing them to absorb the light energy and re-emit it as visible fluorescence. Changes in the natural fluorescence of healthy tissue generally indicate light-scattering biochemical or structural changes caused by developing tumor cells. Health care providers shine the light onto a suspicious sore in the mouth, look through an attached eyepiece, and check for changes in color.  Normal oral tissue emits a pale green fluorescence, while early tumor cells appear dark green to black.  Not only would the instrument be an effective screening adjunct, it may also prove useful for helping surgeons determine how far to extend the surgical borders when removing tissue for biopsies.  In 2008 NIDCR will continue to support the integration and translation of cutting edge technologies and practice protocols that hold great promise to finally improve the early detection and long term survival rates for those who suffer from oral cancer.

Budget Policy:  The FY 2008 estimate for the Integrative Biology program area is $180.2 million, a decrease of $1.4 million, or 0.8 percent from the FY 2007 estimate. The program plans for FY 2008, along with expected outputs, follow. High priority will be given to support ongoing programs such as the one described above, meritorious new investigator–initiated research grants, and research training related to the mission areas described above. In addition, NIDCR will start two new initiatives in the following scientific areas: 

• Systems Biology Approach to Salivary Gland Physiology:  Saliva is a complex mixture of water, buffers, antibodies, and specialized proteins, important for maintaining oral health, function, and comfort.  For example, this remarkable liquid aids in the body’s immune function, digests food, remineralizes tooth enamel, protects the oral mucosa, and helps prevent oral fungal infections.  Previously NIDCR-supported research projects catalogued the genes and proteins that are expressed in the salivary glands.  This could be thought of as similar to assembling a list of cities in the world but having little or no information about their location, culture, or neighboring communities.  This initiative will build on that knowledge by putting the existing salivary gene and protein catalogues into context.  That is, not only will it define when and where these genes and proteins are expressed in the salivary glands, but also how they function as parts of a fully integrated biological system.  This initiative will combine the power of mathematics, biology, genomics, computer science, and other areas to assemble this information.  This highly detailed information will likely translate into more precise and practical leads to treat Sjögren’s Syndrome, a debilitating autoimmune disorder that affects millions of Americans.  The initiative also will help in learning to use saliva as a diagnostic fluid for a variety of conditions, from AIDS to cancer to diabetes.   
   
  
• Osteoimmunology--Crosstalk between Immune System and Bone:  Osteoimmunology represents a rethinking of the traditional divide between bone and immunology research.  This reconsideration results from recent work indicating that bone influences the well-being of our immune system - and vice versa.  The challenge now is to define these interactions throughout the body, including the mouth.  This initiative will provide a fundamental understanding of the biological crosstalk between oral bone and the immune system.  For Americans, this initiative will provide information that has a direct impact on our understanding of the nature, progression, and treatment of periodontal disease, and, most importantly, how best to prevent this condition before it erodes oral bone and causes tooth loss. 

Clinical Research

Even though the Nation’s oral health has never been better, a glance through today’s dental or medical journals clearly shows that a long, challenging road lies ahead before our Nation achieves optimum oral health for all.   NIDCR will support research to expand the scientific evidence available to practitioners for current and future dental and oral health treatments.  The availability of rigorous science-based information will allow practitioners to better match a patient’s specific condition and personal health variables to the most efficacious treatment regimen. As the Nation’s leading supporter of dental and oral health research, NIDCR is uniquely positioned to take the lead in generating this evidence base.

Budget Policy:  The FY 2008 estimate for the Clinical Research Program is $71.7 million, an increase of $2.3 million, or 3.2 percent over the FY 2007 estimate. The program plans for FY 2008 include support for ongoing programs, highly meritorious new investigator–initiated research grants, and research training related to the mission.

• NIDCR will fund a competing renewal of the Oral Health Disparities Centers Initiative due to the promising achievements of currently funded centers, and the magnitude of the need for scientific advancement to eliminate disparities.  Despite the remarkable improvement in the Nation’s oral health over the years, not all Americans have benefited equally.  Oral, dental, and craniofacial conditions remain among the most common health problems for low-income, disadvantaged, and institutionalized Americans.  Unfortunately, there is no easy, one-size-fits-all solution.  Much remains to be learned about the complex array of cultural, economic, genetic, and other contributory factors to these disparities and how best to overcome them.  The NIDCR currently supports five regional Centers for Research to Reduce Oral Health Disparities.  These centers already have devised several innovative, low-cost approaches to address early childhood tooth decay, oral cancer, poor diet, and improper tooth alignment, called malocclusion.  The renewal of the Oral Health Disparities Centers Program in FY 2008 will further NIDCR’s efforts to find ways to eliminate the persistent gaps in oral health that remain in our nation.   
  
  
• Practice-Based Research Networks:   Three regional dental practice-based research networks, or PBRNs, have been established through NIDCR grants.  Their mission is to create networks of practicing dentists and dental hygienists to participate in clinical studies on a variety of pressing clinical issues in oral healthcare.  A new activity for FY 2008 will provide an important and unanticipated benefit to the American people by expanding the evidence base on an emerging public health issue.  Millions of Americans currently take a type of drug called bisphosphonates, typically to ease cancer-related pain or to prevent osteoporosis.  But recent reports indicate that newly formulated bisphosphonates can cause in some people a debilitating condition of the jawbone called osteonecrosis.  What remains unclear is the prevalence of this unwanted side effect and, more importantly, who precisely is at risk.  The NIDCR is launching the needed studies to investigate the problem and provide more meaningful data for the millions of Americans who may be at risk for osteonecrosis of the jaw. 
  
  
• Clinical studies of the potential association between maternal oral health and obstetric outcomes:  In recent years evidence has suggested that a pregnant woman with periodontal (gum) disease might be at increased risk for premature birth.  NIDCR-supported scientists recently completed the largest clinical trial to date to evaluate this possibility, called the Obstetrics and Periodontal Therapy Trial (OPT).  Although OPT is currently the largest study to publish on the subject, NIDCR-supported Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) study is ongoing and will continue into FY 2008.  There are some differences between the two studies.  The 1,800-patient MOTOR study involves a broader socio-economic cross section of women, provides fewer basic dental services, and includes women with slightly less severe periodontal disease.  Conducting more than one large clinical trial on this important public health question will cast a wide enough investigational net to determine which, if any, women are at risk.
  
  
• Orofacial Pain:  Prospective Evaluation and Risk Assessment (OPPERA):  This five-year clinical study continues into FY 2008 and will greatly accelerate the identification of better treatments to control the pain of temporomandibular muscle and joint disorders (TMJD), a group of conditions that cause pain and dysfunction in the jaw joint and muscles that control jaw movement.  The OPPERA study marks one of the first, if not the first large, prospective clinical study of a chronic pain disorder.  A prospective study is the “gold standard” of medical research: it looks forward in time, monitoring the health of those in the study over several years to track the onset or progression of a disease.   This study will open a much needed window on these extremely complex conditions.  With this five-year vantage point, it will be possible to begin identifying individual genetic, physiologic, and psychological factors that cause or contribute to TMJ disorders.  In addition to our investment in OPPERA,  NIDCR’s continued investment in this area for FY 2008 includes several program announcements that will advance virtually all aspects of understanding and caring for these disorders.   

Biotechnology and Innovation

NIDCR supports research on the next generation of breakthrough biomedical technologies that will improve oral health. To accelerate technology development, the Institute relies on interdisciplinary research approaches with an emphasis on basic and translational studies.  Biomimetics (the use of biological systems as models to develop synthetic substances, devices, or systems), nanotechnology and nanoscience, diagnostic technologies, stem cell research, bioinformatics, dental materials, and biocompatibility of engineered materials—all fall within the sphere of this research area.  Achievements that promise to make real what once seemed impossible loom on the horizon.  However, these discoveries will improve health and quality of life only if they are incorporated into everyday practice; for that reason technology transfer is an important part of this program area.  To that end, activities to fast-track small business innovation grants are planned for FY 2008, thus speeding the translation of scientific findings into practice.

Budget Policy:  The FY 2008 estimate for the Biotechnology and Innovation program area is $53.9 million, a decrease of $0.4 million, or 0.8 percent from the FY 2007 estimate. Priority will be given to support of ongoing programs and highly meritorious new research projects.  For this program, a significant portion of the FY 2008 budget will be targeted toward the following two areas:

• Salivary diagnostics:   The NIDCR stands at the forefront of efforts to develop salivary diagnostics, the use of saliva as a diagnostic fluid.  Several Institute grantees are now working to develop the various constituent parts required to assemble a tiny automated machine that can precisely measure levels of the various antibodies, antigens, and nucleic acids present in saliva, all of which may indicate a developing disease or condition.  In contrast to existing blood tests, salivary tests will able to be performed on the spot and require no painful needle sticks.  Recently, the promise of salivary diagnostics moved closer to becoming technologically feasible.  NIDCR grantees fabricated the first disposable, low-cost miniaturized diagnostic platform to process small amounts of saliva, amplify its DNA, and detect the levels of DNA sequences of interest.  During FY 2008 work will proceed to integrate this back-end platform with existing front-end technologies to ultimately create a fully functional hand-held instrument for salivary diagnostic tests.  
   
• Biomaterials:  This field of research includes a number of promising areas of investigation—for example, engineering more biocompatible materials to act as scaffolding for replacement bone and teeth; the use of nanoparticles to increase the strength and durability of dental filling materials; and the design and development of effective bioadhesives for mineralized tissues such as dental enamel and bone, an area of investigation for FY 2008, made possible by recent progress.  A waterproof, all-purpose adhesive that is secreted by mussels first intrigued biomedical and dental materials scientists a few decades ago.  However, attempts to mimic mussels were slowed by an inadequate understanding of the molecular underpinnings of the adhesion.  As new and more powerful research technologies emerge, these underpinnings are starting to come into focus. In a groundbreaking study, NIDCR grantees recently defined the adhesive qualities of a single amino acid called dopa that is prominent in mussel glue.  This new understanding will pave the way for a new generation of bioadhesives.  FY 2008 investments in the area of biomaterials will speed that progress. 

Intramural Research Program

The NIDCR’s Division of Intramural Research (DIR) continues to be extremely productive in an incredible array of research areas.  Using the latest techniques in biomedical science - molecular biology, immunology and cell biology - researchers investigate the biochemistry, structure, function and development of bone, teeth, salivary glands and connective tissues; the role of bacteria and viruses in oral disease; genetic disorders and tumors of the oral cavity; the cause and treatment of acute and chronic pain; and the development of new and improved methods to diagnose oral disease.   

Budget Policy:  The FY 2008 estimate for the DIR Program area is $56.7 million, a decrease of $0.4 million, or 0.7 percent from the FY 2007 estimate.  In FY 2008 NIDCR will continue to support its superlative intramural research program, building upon the outstanding progress made to date.  This work will include the following FY 2008 activities:

• Basic Science Investigating Taste Sensation:  NIDCR scientist Dr. Nicholas Ryba and his collaborators will continue pursuit of their goal to understand the organization and control of taste signaling, including not only individual pathways involved in taste transduction function, but how they interact with each other as well.  Thus far, the scientists have discovered the specific proteins and cells in our mouths that detect the everyday tastes of sweet, bitter, savory, and sour, setting the stage for pursuit of their long-term goals of defining the various components and the organization required for taste responses both peripherally and centrally, and elucidating the logic of taste coding.  These discoveries will ultimately open the door to engineer better natural additives to control appetite and/or enhance or alter the flavor of our food.
  
  
• Mechanisms of Pain:   An integral component of NIDCR’s intramural program is unraveling the mystery of nociception, the sensory component of pain. It depends in part on the intricate sensory neural network within our bodies, stretching from our extremities to the spinal cord and on to the brain. But on its most fundamental level, nociception involves molecules and chemical mechanisms.  An established area of intramural investigation that NIDCR will pursue further in FY 2008 is the role of the protein called cyclin-dependent kinase 5 (Cdk5).  Recently, Dr. Ashok Kulkarni, along with other NIDCR scientists and their NIH colleagues reported the first direct evidence that Cdk5 plays a regulatory role in pain signaling between sensory nerves in the spinal cord and nerve ganglia. These findings point the way for additional research in FY 2008, suggesting that new analgesic drugs that alter Cdk5 activity one day may be beneficial in treating pain. 

   
Research Management and Support

This budget category supports the scientific and administrative management structures needed to effectively lead and manage the world’s largest oral health research enterprise.  The Institute’s extramural staff scientists and grant specialists maintain liaison with nearly 800 grantees, and provide stewardship for the Institute’s $340 million investment in research and research training grants.  Additionally, NIDCR conducts formal evaluations of its intramural and extramural research programs.  These evaluations are designed to inform leadership and advisory bodies on scientific progress and new research directions in the quest to strengthen our Nation’s health. 

This budget category also supports the Institute’s health communication activities.  The NIDCR Office of Communications and Health Education produces and disseminates informational materials on a wide variety of topics, ranging from children’s oral health,  oral cancer, and periodontal disease to oral health care for people with disabilities.  Some materials are geared toward patients or the general public; others are targeted to health care professionals, teachers, or caregivers for special needs patients.  The Office also disseminates information about significant research advances to the media, patient support organizations, professional organizations and the research community

Budget Policy:  The FY 2008 estimate for the Research Management and Support program area is $22.1 million, an increase of $0.2 million, or 1.0 percent over the FY 2007 estimate. The NIDCR will use these resources to fund the scientific and administrative management and oversight activities of the Institute to fulfill its responsibilities as a steward of funds being invested in research to better the health of the American people.