DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

Fiscal Year 2006 Budget Request

Witness appearing before the

House Subcommittee on Labor-HHS-Education Appropriations

Lawrence A. Tabak, D.D.S., Ph.D.

National Institute of Dental and Craniofacial Research

March 9, 2005

William Beldon, Deputy Assistant Secretary, Budget

Number range CHAPTERMr. Chairman and Members of the Committee:

I am pleased to present the President's budget request for the National
Institute of Dental and Craniofacial Research (NIDCR) for Fiscal Year
(FY) 2006. The FY 2006 budget includes \$393,269,000, an increase of
\$1,440,000 over the FY 2005 level of \$391,829,000 comparable for
transfers proposed in the President's Request.

**THE ROAD AHEAD: MERGING SCIENTIFIC VISION**

**AND TECHNOLOGY DEVELOPMENT**

Many of the opportunities that now face our nation's oral health
researchers have never been more exciting or scientifically challenging.
For the first time, we can envision a day when early stage tooth decay
will be reversible with remineralizing solutions that patch the tooth
and halt the disease process before a filling is required. Researchers
will soon begin to learn how to engineer teeth and their constituent
parts in the laboratory and transplant them into the mouth to replace a
missing tooth or damaged tissue. The day also is approaching when saliva
will be a reliable diagnostic fluid to detect systemic diseases,
providing a rapid, non-invasive alternative to blood-based tests. These
are but a few of the many opportunities that await us. And yet, as
important as these visions of the future are in setting the course
toward improved public health, it is abundantly clear that the road
ahead will be blocked unless we develop new tools and technologies for
working within the complex microenvironments of the human body. It is
this merging of scientific vision with technology development that the
NIDCR is fostering within our nation's oral research community and which
I would like to highlight.

**EARLY DIAGNOSIS TO PREVENT DENTAL CARIES**

Let me begin with one of the examples just mentioned. Despite dramatic
reductions in tooth decay in the United States over the last half
century, dental caries remains a significant public health problem,
particularly among disadvantaged population groups. Dental decay also is
an unexpected impediment to timely deployment of military personnel. At
a time when our nation remains at war, dental readiness has been cited
in testimony by the Reserve Officers Association as the number one
deployment problem for National Guard and Reserve members. In a 2002
Department of Defense study, 34 percent of military personnel required
dental care before they could be deployed, compared to only 16 percent
in 1998.

The NIDCR will soon launch an initiative to evaluate the ability of
emerging technologies to accurately and reproducibly measure extremely
subtle changes in dental enamel that signal the earliest phases of
dental caries. While this initiative may sound highly technical, its
outcome could play an essential role in transforming dental care.
Treatments with the potential to remineralize tooth surfaces in the very
earliest stages of decay, long before a filling is needed, are emerging.
In anticipation of the required clinical trials to rigorously evaluate
these treatments, NIDCR will soon launch an initiative to ensure that
microscopic changes in a tooth's mineral content can be measured
accurately and reproducibly. Through this enabling research, the
evaluation of these treatments will be firmly grounded in science,
ensuring the greatest possible benefit to the public.

**BIOENGINEERING: BUILDING A TOOTH**

Tooth loss has been a public health problem in the United States since
the days of George Washington and Thomas Jefferson. Despite
revolutionary advances in oral health over the last half century, tooth
loss remains a problem, particularly among disadvantaged groups. In
addition, tooth agenesis - the lack of one or more permanent teeth - is
the most common congenital malformation in humans. While dental implants
or dentures are often effective replacements, science has progressed to
the point that it may be possible to generate replacement teeth from
scratch, which would mark a truly historic advance in oral healthcare
and in our understanding of human biology.

Whereas just a few years ago tooth regeneration was far beyond the reach
of science, which is no longer the case. An historic opportunity now
awaits dental science to learn to seed and reproducibly control the
complex, tightly orchestrated cellular and molecular interactions
involved in producing a tooth and its supporting structures. The crucial
first steps will be to: identify existing gaps in our knowledge of tooth
formation; pursue viable solutions from throughout the biological and
physical sciences to bridge these gaps; and, based on these
comprehensive analyses, formulate blueprints for a complete tooth.
Relying on the best of these blueprints, interdisciplinary teams of
scientists will begin the process of engineering replacement teeth. It
is likely that these investigations will initially yield viable
replacement parts, such as enamel, dentin or periodontal ligament, but
the ultimate goal is complete tooth regeneration.

**LAB ON A CHIP: SALIVARY DIAGNOSTICS**

Another particularly exciting area of research is salivary diagnostics.
Scientists have long recognized that our saliva serves as a "mirror" of
the body's health, in that it contains the full repertoire of proteins,
hormones, antibodies, and other molecular substances that are frequently
measured in standard blood tests to monitor health and disease. Saliva
is easy to collect and poses none of the risks, fears, or "invasiveness"
of blood tests. The problem has been that the needed technologies have
not existed to adequately develop salivary diagnostics on a large scale.

The Institute continues to support a major research effort that will
further develop these needed technologies and create the first
comprehensive baseline catalogue of all proteins found normally in oral
fluids. This is the initial step in building the needed scientific
infrastructure required to expand salivary diagnostics. Already,
scientists have begun to evaluate which of the myriad gene products in
saliva correlate with various disease processes.

The NIDCR envisions that this basic research could one day translate
into miniature, hi-tech tests, or so-called "labs" on a silicon chip,
which rapidly scan oral fluids for the presence or absence of multiple
proteins linked to various systemic diseases and conditions. Given the
ease of sample collection and the breadth of protein markers that could
be arrayed on the silicon chip, salivary tests have the potential to
revolutionize how diseases are diagnosed. Physicians and dentists would
continue to diagnose diseases. But they would be in the position for the
first time to monitor a patient's health, producing a comprehensive
molecular print out of that individual's health status that can be
assessed over time.

Salivary diagnostics will have benefits far beyond medicine and
dentistry as well. Law enforcement agencies could employ saliva tests in
the field to determine rapidly whether a person is intoxicated or has
recently used illegal drugs. These tests may also be beneficial in
determining exposures to environmental, occupational, and biological
substances, such as anthrax.

**ORAL CANCER: EARLY DETECTION IS KEY TO SAVING LIVES**

The field of salivary diagnostics recently yielded exciting early
findings related to oral cancer detection. According to the American
Cancer Society and the Centers for Disease Control and Prevention, oral
cancer is the seventh most common cancer among U.S. males and ranks
fourth among African American men. Unfortunately, survival rates have
not improved significantly in decades. A patient's chance of survival is
improved significantly with early detection and treatment. A team of
NIDCR-supported scientists at the University of California at Los
Angeles recently reported that they could measure elevated levels of
four distinct cancer-associated molecules in saliva and distinguish
within 91 percent accuracy between healthy people and those diagnosed
with oral squamous cell carcinoma. This "proof-of-principle" study marks
the first report in the scientific literature that distinct patterns of
"messenger RNA" are not only measurable in saliva, but can indicate a
developing tumor. These initial results highlight the potential clinical
value of saliva and hold out exciting possibilities for development of
commercially available tests capable of delivering early, reliable,
non-invasive detection of developing tumors.

**PAIN: TRANSLATING TARGETS INTO TREATMENTS**

Sizeable gaps exist in our understanding of some of the most basic cells
involved in the pain process. Prime examples are the glial cells. For
decades, scientists assumed that glial cells primarily played a
supportive role in the central nervous system and had no direct
influence on the transmission of sensory signals to the brain. But, as
more powerful analytical molecular tools have emerged in recent years,
scientists now realize that glial cells play a far more important role
in pain than was previously appreciated. With this new awareness, it
becomes imperative to better define the biology of these cells and their
roles in regulating certain aspects of nervous system function.

The NIDCR will launch an initiative that will stimulate needed research
into the basic biology of glial cells and their interactions with
neurons in causing orofacial pain disorders, such as temporomandibular
joint disorders. The initiative will encourage multidisciplinary studies
in a variety of areas to define more broadly than ever important aspects
of the pain process. Based on this broad investigative approach, key
aspects of the pain process will be more clearly defined, pointing the
way to unique and highly specific molecular targets for drug
development. Without identifying these additional targets, it will be
impossible to ever adequately control or treat pain, particularly among
the estimated 10 percent of Americans who suffer from chronic pain.

**NIH ROADMAP**

The NIH Roadmap themes are synergistic with NIDCR research initiatives
and provide added impetus to the efforts of oral health researchers. For
example, the theme *Re-engineering the Clinical Research Enterprise* is
particularly relevant to the development of NIDCR-sponsored dental
Practice Based Research Networks. Similarly, the goals of the initiative
*Building Blocks, Biological Pathways and Networks* are closely linked
to NIDCR's own bioengineering initiative, "Building a Tooth." *Research
Teams of the Future* provides an opportunity to further integrate
dentists into the new clinical research structure, and highlights
NIDCR's longstanding efforts to encourage multi- and interdisciplinary
approaches to research questions.

With the above-mentioned examples and other research progress, such as
in salivary gene transfer, defining the oral biofilm, and the molecular
targeting of oral cancer, NIDCR has never faced more exciting
opportunities. By merging our vision of the future with technology
development, the road ahead will lead this nation to a new generation of
progress and improved oral health.

Thank you, Mr. Chairman. I would be pleased to answer any questions that
the Committee may have.

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

Biographical Sketch

NAME Lawrence A. Tabak

POSITION Director, National Institute of Dental and Craniofacial
Research

BIRTHPLACE Brooklyn, New York

DATE December 15, 1951

EDUCATION B.S., Biology and Chemistry, City College of CUNY, 1972

D.D.S., Dentistry, Columbia University, 1977

Ph.D., Oral Biology, SUNY at Buffalo, 1981

Certified in Endodontics, SUNY at Buffalo, 1985

EXPERIENCE

2000-present Director, National Institute of Dental and Craniofacial
Research, NIH

2000-present Senior Investigator, National Institute of Diabetes and
Digestive

and Kidney Diseases, NIH

2000 Adjunct Professor of Dentistry and of Biochemistry and

Biophysics, University of Rochester

1998-2000 Senior Associate Dean for Research, School of Medicine and

Dentistry, University of Rochester

1998-2000 Co-Director, Institutional Medical Scientist Training Program

(MSTP)

1998-2000 Professor of Dentistry and of Biochemistry and Biophysics

1998-2000 Director, Center for Oral Biology, Aab Institute of Biomedical

Sciences, University of Rochester

1996-2000 Director, Institutional Dentist Scientist Program

1996-1997 Professor, Dental Research and Biochemistry and Biophysics,

University of Rochester

1995-1997 Chair, Department of Dental Research, University of Rochester

1992-1996 Professor, Dental Research and Biochemistry, University of

Rochester

1988-1994 Director, Graduate Study, Department of Dental Research,

University of Rochester

1986-1992 Associate Professor, Dental Research and Biochemistry,

University of Rochester

1985-1986 Associate Professor, Endodontics and Oral Biology, SUNY/

Buffalo

1985-1986 Director, Graduate Study (Ph.D.), Oral Biology, SUNY/

Buffalo

1982-1983 Visiting Scientist, NIDR, Bethesda, MD

1981-1985 Assistant Professor, Endodontics and Oral Biology, SUNY/

Buffalo

1980-1981 Assistant Professor, Oral Biology, SUNY/Buffalo

HONORS AND AWARDS

2002 Elected Member of the Institute of Medicine

1998 Fellow of AAAS

1997-2000 USPHS MERIT Award (R37)

1997 Alumnus of the Year, School of Dental and Oral Surgery,

Columbia University

1996 IADR Distinguished Scientist Award -- Salivary Research

1994 Manuel D. Goldman Prize for Excellence in First Year Teaching,

School of Medicine and Dentistry, University of Rochester

1994-1997 Dean's Senior Teaching Fellow, School of Medicine and

Dentistry, University of Rochester

1993 Alumni Award for Excellence in Graduate Education, University

of Rochester

1991 Salivary Research Award (Salivary Research Group, IADR)

1987 IADR Young Investigator Award

1984-1989 USPHS Career Development Award (K04)

1984 Student Research Association Award (SUNYAB)

1982-1985 USPHS New Investigator Award (R23)

1980-1982 Cystic Fibrosis Foundation New Investigator Award

**Department of Health and Human Services**

**Office of Budget**

**William R. Beldon**

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in
the Department of Health and Human Services. He has been a Division
Director in the Budget Office for sixteen years, most recently as
Director of the Division of Discretionary Programs. Mr. Beldon started
in federal service as an auditor in the Health, Education and Welfare
Financial Management Intern program. Over the course of more than 30
years in the Budget Office, Mr. Beldon has held Program Analyst, Branch
Chief and Division Director positions. Mr. Beldon received a Bachelor's
Degree in History and Political Science from Marshall University and
attended the University of Pittsburgh where he studied Public
Administration. He resides in Fort Washington, Maryland.