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150 years of progress

Highlights of Americas scientific
contribution to dentistry and
dental practice

This special supplement to The Journal of the American Dental

Association was made possible through an educational grant
from A-dec, ADA Insurance Plans from Great-West Life, ADA
Members Retirement Program, the Colgate-Palmolive Company
and the Wm. Wrigley Jr. Company.


Highlights of Americas Scientific Contributions

to Dentistry: 150 Years and Still Counting
B.L. Pihlstrom
The guest editor of this special supplement to JADA highlights
some of Americas scientific contributions to dentistry in the
past 150 years.


The Evolution of Americas Scientific Advancements

in Dentistry in the Past 150 Years
J.L. Gutmann
The author examines scientific advancements in dentistry in the
United States. This article includes a sidebar about the
contributions of the ADA Foundations Paffenbarger Research Center.


Science Is the Fuel for the Engine of Technology and Clinical

M.L. Snead, H.C. Slavkin
The authors highlight prominent scientific discoveries of the past 50 to 60
years that have improved the quality of life for patients.


The Biology, Prevention, Diagnosis and Treatment of Dental Caries:

Scientific Advances in the United States
D.T. Zero, M. Fontana, E.A. Martnez-Mier, A. Ferreira-Zandon, M. Ando,
C. Gonzlez-Cabezas, S. Bayne
The authors outline major scientific advances in cariology during the past 150
years, with an emphasis on contributions made by people living and working
in the United States.


The Biology, Prevention, Diagnosis and Treatment of Periodontal

Diseases: Scientific Advances in the United States
G.C. Armitage, P.B. Robertson
The authors provide an overview of scientific advances in periodontology
during the past 150 years.


A View of the Future: Dentistry and Oral Health in America

I. Garcia, L.A. Tabak
The authors explore advances in modern science and technology and how
they will change oral health care in the future.

JADA, Vol. 140

September 2009



Michael Glick, DMD, professor of oral medicine,
Arizona School of Dentistry & Oral Health; associate
dean for oral-medical sciences, School of Osteopathic
Medicine in Arizona, A.T. Still University, Mesa

Laura A. Kosden

James H. Berry

Lisbeth R. Maxwell


Janice Snider, Amy E. Lund

Bruce L. Pihlstrom, DDS, MS, professor emeritus,

Department of Surgical and Developmental Sciences,
School of Dentistry, University of Minnesota,
Minneapolis; associate editor for research,
The Journal of the American Dental Association



Joe Hoyle

Peter Solarz
Editors Office (Mesa, Ariz.): Vicki Hodge
Publishers Office (Chicago): Karen London

Dentistry and Medicine

Peter B. Lockhart, DDS

Patricia A. Lewis

Esthetic and Restorative Dentistry

David C. Sarrett, DMD, MS

Karen London

Carol J. Krause

Evidence-Based Dental Practice

James D. Bader, DDS, MPH


Michelle Boyd


Shirley Hawkins

Paul S. Casamassimo, DDS, MS


Lois Cohen, PhD

Angela James

Raul I. Garcia, DMD


Jill Philbin

Mel L. Kantor, DDS, MPH


Dushanka V. Kleinman, DDS, MScD

Gwen Johnson

William G. Kohn, DDS, MPH


Gilbert X. Muoz

Vincent G. Kokich, DDS, MSD


Laura Kottemann, DMD

Liz Grace

Daniel Malamud, PhD


Paul Gorski

Kevin J. McNeil, DDS


Terry G. OToole, DDS

Cindy Carstensen

Titus Schleyer, DMD, PhD


Ann Allen

Gordon P. Trowbridge III, DMD

Cover illustration by Peter Solarz

Cover photo 2009 Jupiterimages Corporation



All statements of opinion and of supposed fact are published

under the authority of the authors, including editorials and letters. They are not to be accepted as the views of the American
Dental Association or its subsidiaries unless such statements
have been expressly adopted by the Association. Articles are
accepted with the understanding that they have not been published previously and that they are submitted solely to The
Journal. Information on any products mentioned may be available
from the authors. Neither the American Dental Association nor
any of its subsidiaries has any financial interest in any products
mentioned in editorial content, and The Journal requires all
authors to disclose any financial or other interests they may have
in products or services described in their articles.

All advertising appearing in ADA publications must comply with

official published advertising standards of the American Dental
Association. The publication of an advertisement is not to be construed as an endorsement or approval by the American Dental
Association or any of its subsidiaries, councils, commissions or
bureaus of the product or service being offered in the advertisement unless the advertisement specifically includes an authorized
statement that such approval or endorsement has been granted.
A copy of the advertising standards of the American Dental Association is available on request.


JADA, Vol. 140

September 2009

Copyright 2009 American Dental Association. All rights

reserved. For inquiries regarding reprints and permissions,
contact Karen London at 1-312-440-2787.

Highlights of Americas scientific

contributions to dentistry
150 years and still counting
Bruce L. Pihlstrom, DDS, MS

s we celebrate the 150th anniversary

of the American Dental Association
(ADA), can you imagine how dentistry
was practiced and what oral health
was like in America one year before
Abraham Lincoln was elected president and two
years before the start of the American Civil War?
Although the worlds first dental school, the Baltimore College of Dentistry, had opened in 1840,
most dentists at that time were self-taught or had
received training as apprentices.
Because soldiers in the Civil War needed anterior teeth to open paper cartridges for their guns,
the Union Army classified recruits and draftees as
being handicapped if they lacked four incisors;
their records were designated 4F, an abbreviation
that later came to signify any medical reason for
draft deferral.1 Although it has been reported that
relatively few men actually were rejected owing to
a lack of teeth, when Sherman reached Savannah,
Ga., many troops sought dental care and one dentist reported that the emergency need alone would
have required 100 dentists to work 6 months on
these troops.1
This supplement to The Journal of the American
Dental Association celebrates Americas truly
amazing scientific contributions to dental practice
and oral health since the founding of the ADA.
Owing to, in no small part, Americas scientific contributions to dentistry, we now are on the brink of
a remarkable transformation that promises to
expand dramatically the role of dental professionals and improve the oral health of people
throughout the world.
Scientific advances have changed society and
dentistry in ways that no one could have imagined
during the Civil War, at the beginning of the 20th
century or even just a few years ago. Dentistry was
an empirical endeavor when the ADA was founded;
its originators were aware of the lack of a scientific
basis, and they sought to improve the standards
and quality of the profession through scientific
investigation.2 Near the beginning of the 20th cen-


JADA, Vol. 140

September 2009

tury, Willoughby Miller recognized the role of bacteria in caries and periodontal disease,3,4 but it
would be many years before his observations were
accepted and many more before oral disease prevention was practiced widely.
Many scientific advances have led to better oral
health and improved dental care since the founding
of the ADA. However, it is impossible to include in
this supplement all of the developments that
occurred during the 150-year period, including discoveries such as safe and effective pain control,
high-speed dental instrumentation, dental
implants, advances in the diagnosis and treatment
of oral cancer, and numerous advances in the
dental specialties. Instead, this supplement focuses
on selected topics, with an emphasis on developments in the last 50 to 60 years. These topics
include the following:
dthe evolution of oral health science in the
United States;
dthe role of basic science in transforming technology and dental practice;
dscientific advances in the biological understanding, prevention, diagnosis and treatment of
dental caries and periodontal disease.
This supplement also includes a view of the
exciting future that science likely will bring to dentistry and oral health care. It describes the evolution
of oral health science in the United States and the
transformative role of basic science in technology
and dental practice, because they transcend all areas
of dentistry. In addition, it includes discussion of scientific advances in dental caries and periodontal disease, because these diseases are responsible for the
vast majority of oral disease and tooth loss. Science
is an international endeavor, with no geopolitical
boundaries, and we recognize that investigators outside the United States have made many seminal discoveries and contributions to dentistry. However,
because this supplement specifically commemorates
the 150th anniversary of the ADA, the authors
emphasize contributions of scientists who lived and
worked in the United States.


Dr. Gutmann5 describes how the stage was set in

the early 20th century for the scientific evolution of
dentistry. The contributions of Horace Wells,
William Morton, G.V. Black, Willoughby Miller,
Edward Angle and others were important, but the
seminal events that led to the scientific basis of
dentistry in the United States include the following:
dthe vision of William J. Gies and the 1926 Carnegie
Foundation report6 regarding dental education;
dthe development of scientific dental journals and
the publication of scientific findings in mainstream
scientific and medical journals;
dthe role of immigrant dental scientists and the
development of oral biology as a discipline;
dthe establishment of the National Institute of
Dental Research in 1948.
Without these critical developments, oral health
research could not have flourished in this country.

In their review of the role of basic science in technology development and dentistry, Drs. Snead and
Slavkin7 discuss how science fuels the engine of
innovation and discovery. They provide three fascinating examples of dentists who transformed medicine in the last 50 to 60 years:
dNorman Simmons refined the techniques of isolating DNA, which Rosalind Franklin used to
create the first x-ray crystallography images from
DNA and which led James Watson, Francis Crick
and Maurice Wilkins to predict the structure of
DNA in 19538;
dRobert Ledley pioneered computerized tomographic scanning in the early 1950s,9,10 a remarkable achievement that led to modern diagnostic
imaging in both dentistry and medicine;
dRussell Ross and colleagues first proposed that
atherosclerosis is an inflammatory lesion caused by
localized injury to the lining of the arterial wall.11,12
Drs. Snead and Slavkin also discuss recent
breakthroughs in the digital revolution that have
given us the new field of bioinformatics and the
amazing capacity for diagnostic imaging. Genomics
and proteomics continue to progress at a rapid
pace, making it possible for researchers to determine the full complement of genes and proteins
that make us who we are. Personalized medicine
and dentistry are becoming a reality, enabling
clinicians to make diagnostic, prognostic and therapeutic decisions on the basis of a patients genetic
makeup and environmental exposures. Stem cell

biology holds the promise of regenerating lost

tissues and organs, making it likely that dental
implants, as used today, will become obsolete. As
basic science gives us the knowledge and tools to
understand clinical conditions, it promises to establish the foundation for new diagnostic tests,
methods of prevention and therapies that improve
the quality of life for our patients.

Dr. Zero and colleagues13 describe scientific

advances in cariology during the past 150 years
that have led to our understanding of dental caries
as a chronic, dietomicrobial, site-specific disease
caused by a shift from protective factors favoring
tooth remineralization to destructive factors
leading to demineralization. Once a ubiquitous disease, dental caries changed in the last century and
now is unequally distributed. Minorities, homeless
people, migrants, children with disabilities, and
socioeconomically disadvantaged people experience
the highest prevalence and severity of caries.
We have learned much about the microbial etiology of caries and the role of carbohydrates in its
pathogenesis. We also have learned that salivary
factors and genetic-environmental interactions are
important in the etiology of caries. During the last
60 years, we have come to better understand the
central role of fluoride in preventing caries and the
importance of caries risk assessment. Today, we
are able to remineralize early carious lesions, and
new diagnostic imaging methods may enhance our
ability to identify and treat early lesions without
the use of a handpiece or surgical intervention.
Many novel restorative materials and treatment
methods for caries have resulted from strong partnerships between academic, corporate, associationbased and governmental scientists. Unfortunately,
despite the gains made during the last 150 years,
dental caries remains a significant problem for
many Americans, and we look forward to the day
when people of all ages and backgrounds will view
dental caries as a disease of the past.

Drs. Armitage and Robertson14 note that most significant scientific advances in periodontology have
come about as a result of the collective efforts of
visionary pioneers and through multidisciplinary
collaborations between scientists, clinicians, organized dentistry, academia, industry and government. Relatively recent advances in periodontology
have changed fundamentally how clinicians detect
JADA, Vol. 140

September 2009


and treat gingivitis and periodontitis. We now

know that these diseases are biofilm-induced infections and that the host response plays a major role
in determining the damaging effects of these diseases. We know that prominent risk factors for
periodontal disease include socioeconomic status,
tobacco use, diabetes and genetic influences.
Randomized controlled trials have shown that
most conventional forms of periodontal therapy,
combined with posttreatment maintenance programs, are effective in controlling or eliminating
these diseases. Moreover, biological knowledge
gained from research regarding periodontal tissue
repair and regeneration has been translated from
the laboratory into clinical practice. Advances in
molecular biology, human genetics, proteomics and
stem cell biology have set the stage for the predictable regeneration of periodontal tissues.

JADA, Vol. 140

The vision of the ADA Future of Dentistry report

to achieve improved health and quality of life for
all through optimal oral health16remains a
worthy goal for our profession. There is no question
that science will lead to new technologies for diagnosing, preventing and treating oral and craniofacial diseases and disorders. However, given the
complexities of our health care delivery system and
the economic and cultural differences in our society,
practitioners, policymakers and dental educators
must make a substantive and concerted effort to
apply these new discoveries in ways that improve
the oral health of all those who live in our nation.
Dr. Pihlstrom is a professor emeritus, Department of Surgical and
Developmental Sciences, School of Dentistry, University of Minnesota,
Minneapolis. He also is the guest editor of this supplement. Address
reprint requests to Dr. Pihlstrom, 4801 Fairmont Ave., #902, Bethesda,
Md. 20814, e-mail
Disclosure. Dr. Pihlstrom did not report any disclosures.

Lastly, Drs. Garcia and Tabak15 describe their view

of the future of dentistry and oral health. They
envision a time when dental handpieces will be
obsolete and when dentists use molecular methods
to predict and prevent oral disease. For the first
time in human history, there is the real possibility
that we will be able to alter the course of disease by
manipulating defective genes and using targeted
drugs and therapies to tailor treatment on an individual basis rather than using the one-treatmentfits-all approach that is common today.
The future dental office likely will be a place
where visual and tactile methods of diagnosing disease will be augmented by technologies such as
smart imaging systems, genome scans, molecularly
based diagnostics and integrated electronic risk
management systems. Drs. Garcia and Tabak also
predict that dentists of the future likely will rely on
diagnostic and treatment tools that rapidly and
reliably process a patients biological information
from their genes to their proteins and metabolites.
They also look forward to the day when patients
who suffer from chronic orofacial pain will be
treated with new patient-specific nonaddictive pain
medications that maximize efficacy and safety
while avoiding dangerous side effects.
However exciting these new technologies may
be, Drs. Garcia and Tabak emphasize that we
must continue to improve the translation and
dissemination of new discoveries into tools for
communities and people at greatest risk of developing disease. Failing to do so could lead to persistent or even increased disparities in oral health
in America.


September 2009

Many thanks are due to the authors and anonymous peer reviewers of
the articles in this supplement and to the staff of The Journal of the
American Dental Association, the ADA Department of Library Services,
the Paffenbarger Research Center and the National Institute of Dental
and Craniofacial Research. All unselfishly shared their time and expertise to make this supplement possible.
The financial support of the sponsors that made this supplement a
reality is gratefully acknowledged.
1. Dammann G, Bollet AJ. Images of Civil War Medicine: A Photographic History. New York City: Demos Medical Publishing; 2008:41-42.
2. 125th anniversary commemoration. 1859-1880: the early years.
American Dental Association JADA 1984;108(4):483.
3. Miller WD. Original Investigations Concerning Pyorrhea Alveolaris:
The Micro-Organisms of the Human Mouth. Philadelphia: The S.S. White
Dental Mfg. Co.; 1890.
4. Miller W. The presence of bacterial plaques on the surface of teeth
and their significance. Dent Cosmos 1902;44:425.
5. Gutmann JL. The evolution of Americas scientific advancements in
dentistry in the past 150 years. JADA 2009;140(9 suppl):8S-15S.
6. Gies WJ. Dental Education in the United States and Canada: A
Report to the Carnegie Foundation for the Advancement of Teaching.
New York City: The Carnegie Foundation for the Advancement of
Teaching; 1926.
7. Snead ML, Slavkin HC. Science is the fuel for the engine of technology and clinical practice. JADA 2009;140(9 suppl):17S-24S.
8. Wilkins MHF. The molecular configuration of nucleic acids. Nobel
Lecture, December 11, 1962.
DNA50/source/wilkinslecture.pdf. Accessed July 17, 2009.
9. Ledley RS, Ayers WR. Computerized medical imaging and graphics
evolves from computerized tomography. Comput Med Imaging Graph
10. Ledley RS. Innovation and creativeness in scientific research: my
experiences in developing computerized axial tomography. Comput Biol
Med 1974;4(2):133-136.
11. Ross R, Glomset JA. Atherosclerosis and the arterial smooth muscle
cell: proliferation of smooth muscle is a key event in the genesis of the
lesions of atherosclerosis. Science 1973;180(93):1332-1339.
12. Ross R. The pathogenesis of atherosclerosis: a perspective for the
1990s. Nature 1993;362(6423):801-809.
13. Zero DT, Fontana M, Martinez-Mier EA, et al. The biology, prevention, diagnosis and treatment of dental caries: scientific advances in the
United States. JADA 2009;140(9 suppl):25S-34S.
14. Armitage GC, Robertson PB. The biology, prevention, diagnosis and
treatment of periodontal diseases: scientific advances in the United
States. JADA 2009;140(9 suppl):36S-43S.
15. Garcia I, Tabak LA. A view of the future: dentistry and oral health
in America. JADA 2009;140(9 suppl):44S-48S.
16. American Dental Association. Future of Dentistry. Chicago:
American Dental Association, Health Policy Resources Center; 2001.

The evolution of Americas scientific

advancements in dentistry in the past
150 years
James L. Gutmann, DDS

ajor advances in dentistry during the past 150

years include the use of safe and effective local
anesthetic, radiographs, high-speed instrumentation, new dental materials and dental
implants. It was not until the last 50 years,
however, that science became a prominent component of
dental education and an integral part of dental practice.
The scientific evolution of Americas contribution to dental
practice and science occurred because of many factors, but
four major events had a significant effect on bringing science to dentistry. These included the 1926 Carnegie Foundation for the Advancement of Teaching report1 and the
vision of William J. Gies; the formation of scientific journals; the role of immigrant dental scientists from Europe
and oral biology as a discipline; and the establishment of
the National Institute of Dental Research in 1948.


In the mid-19th century, the United States was viewed

globally as the geographical center of innovation in dentistry, but the innovations were based on applied research
as opposed to more basic science, which flourished in
Europe.2 Early examples of innovations in dentistry in
America include the development of the use of general
anesthetic by Horace Wells, who administered nitrous
oxide to patients so that they would experience little or no
pain during tooth extractions, and the subsequent introduction of ether as another way to induce anesthesia, a
development that often has been attributed to William T.G.
Morton.3 Other notable examples of applied research were
the discovery of the welding property of annealed gold foil
by Robert Arthur, the development of innovative oral surgical methods by Simon Hullihen, the characterization of
oral deformities and procedures for their correction by
Norman Kingsley, the classification of malocclusion and
treatment by Edward Angle, surgical procedures for closure of clefts by Truman Brophy, the use of radiographs to
reveal anatomical and pathological conditions of the teeth
and jaws by C. Edmund Kells, and the major contributions
of Greene Vardiman (G.V.) Black in operative dentistry

JADA, Vol. 140

September 2009

Background. During the last 150 years,
dentistry in the United States faced many challenges as it developed its scientific foundation.
In the latter part of the 19th century, clinical
practice was driven by empirical evidence, and
the first few decades of the 20th century set
the stage for Americas scientific evolution of
Conclusions. Seminal developments in
Americas contribution to science in dentistry
and oral health included the 1926 Carnegie
Foundation for the Advancement of Teaching
report and the vision of William J. Gies; the
development of scientific dental journals; the
role of immigrant dental scientists from Europe
and oral biology as a discipline; and the establishment of the National Institute of Dental
Research in 1948.
Clinical Implications. Due in large part
to Americas contribution to dental science and
practice, we are at the brink of a transformation that may expand the role of the dental
profession dramatically and improve the oral
health of people throughout the world.
Key Words. Dental science; dental practice;
history of dental science.
JADA 2009;140(9 suppl):8S-15S.

Dr. Gutmann is a professor emeritus, Department of Restorative

Sciences, Baylor College of Dentistry, Texas A&M University Health
Science Center, Dallas, and maintains a private practice limited to
endodontics, Dallas. Address reprint requests to Dr. Gutmann
at 1416 Spenwick Terrace, Dallas, Texas 75204-5529, e-mail

and oral pathology.4,5 Even in light of these developments, however, skeptics such as Alton Howard
Thompson from Topeka, Kan., challenged the empirical basis of dentistry as it was practiced in the
19th century.6
Willoughby D. Miller, who received his Doctor of
Dental Surgery degree from the University of Pennsylvania, Philadelphia, in 1879, was one of the first
true American dental scientists. His seminal 1890
publication, The Micro-Organisms of the Human
Mouth: The Local and General Diseases Which Are
Caused by Them, 7 reported that when carbohydrates are mixed with saliva and incubated at 37C,
they generated lactic acid that could decalcify an
entire tooth crown. He also identified
several bacteria that created acids
during their metabolism, presented
various proposals regarding the role of
bacteria in oral disease and proposed
that saliva could be used for research.
Perhaps most importantly, he
attempted to reorient the dental profession from focusing on treatment to
focusing on disease prevention.
Although many people were at the
forefront of dentistry as an evolving
science in the United States, the following deserve special mention: G.V.
Black, Truman Brophy, Edmund
Dr. William J. Gies
Noyes, Charles N. Johnson, Thomas
Gilmer, W.G. Skillen, Edgar D. Coolidge, Balint
Orban, Frederick B. Moorehead, Edward H. Hatton
and S.D. Tylman. Many of these people were associated with schools in the Chicago area, including
the Chicago College of Dental Surgery at Loyola
University; Northwestern University Dental School;
and the University of Illinois, College of Dentistry.
The development of science that would define the
essence of dentistry as a whole, beyond that of a
technical or empirical profession, had its roots in the
late 1800s and early 1900s, and major benchmarks
that affected contemporary dentistry in the third to
the fifth decades of the 20th century were set. Before
the late 1800s and early 1900s, dentistry in the
United States was recognized throughout the
Western world for its technical excellence, but it was
not recognized generally as having a scientific basis.

In 1926, the Carnegie Foundation for the Advancement of Teaching published a report by William J.

Gies, a professor of biological chemistry at Columbia

University, New York City, that encouraged faculty
to conduct research in dental schools and include a
scientific basis for dentistry in the curriculum.1 The
report urged U.S. and Canadian dental schools to
improve their curricula by employing well-trained
and full-time teachers, by encouraging and conducting research and by providing adequate
libraries.1 In 1928, the American Dental Association
(ADA) created the National Board of Dental Examiners, and dental school graduates began taking
examinations in the basic sciences and the mechanical aspects of dentistry.3
Gies proposed that predental and dental educational requirements should include a
minimum of two years of college before
entry into dental school; however, it
was not until 1937 that prospective
dental students were required to have
two years of college.3 Furthermore, Gies
called for dentists to receive graduatelevel instruction after graduating from
dental school, for more complete dental
libraries, for better cooperation between
dentistry and medicine, for the elimination of independent or proprietary
dental schools, and for the affiliation of
dental schools with private or statesupported universities.8 He also called
for increased financial support for
dental education and for dental educators to have a
greater appreciation for the biological and medical
aspects of dentistry.
Gies envisioned an organization in which all
research-oriented people could promote interest in
dental research. On Dec. 20, 1920two years after
the formation of the Journal of Dental Research
(JDR)Gies and 24 colleagues organized the International Association for Dental Research (IADR) to
bring together dentists and scientists to enhance
dental research.4,8 The North American Division of
IADR first met in 1952. In 1970, the North American Division had 2,102 members from the United
ABBREVIATION KEY. FDI: Fdration Dentaire Internationale. IADR: International Association for Dental
Research. JADA: The Journal of the American Dental
Association. JDR: Journal of Dental Research. NDA:
National Dental Association. NIDCR: National Institute
of Dental and Craniofacial Research. NIDR: National
Institute of Dental Research. NIH: National Institutes of
Health. NIST: National Institute of Standards and Technology. PRC: Paffenbarger Research Center.
JADA, Vol. 140

September 2009


States, Canada and Mexico.4 This division consisted

of 37 sections with councilors to IADR. The division
existed only on paper until it was formally activated
in 1972.4 Helmut Zander, an immigrant dental scientist from Germany who was one of the leaders in
the transformation of American dentistry into a science, was the first president of the North American
Division. Since its inception, IADR has played a critical role in the scientific evolution of dentistry in the
United States and has been a staunch advocate for
U.S. governmental funding of oral and craniofacial
research through the National Institute of Dental
and Craniofacial Research (NIDCR).

Dental journals had a significant influence on the

advancement of dental science. The first dental periodical, the American Journal of Dental Science, was
introduced in 1839; it was renamed the American
Journal and Library of Dental Science in its second
volume. Other early dental publications were Stocktons Dental Intelligencer, The New York Dental Recorder, The Dental Register of the West, Southern
Dental Journal, The Dental Review, Dental Items of
Interest and the Dental News Letter, which was renamed Dental Cosmos in 1859.3 Dental Cosmos, under the auspices of the S.S. White Manufacturing
Company, Philadelphia, published a wide range of
subject matter, including historical accounts, practitioners techniques and opinions. Much of its content
was empirical.
In 1913, the Official Bulletin of the National
Dental Association (NDA) was introduced, and it
was renamed The Journal of the National Dental
Association in 1915. When the name of the NDA
was changed to the American Dental Association
in 1922, the journals name was changed to The
Journal of the American Dental Association
(JADA). In 1932, African American dentists formed
a national association called the National Dental
Association. In 1936, JADA merged with Dental
Cosmos, and the first joint edition was published
in 1937.
The journals of the New York Institute of Stomatology, American Academy of Dental Science, Harvard Odontological Society and Metropolitan District (Massachusetts State Dental Society) combined
in 1906, and in 1912 their quarterly journal became
known as The Journal of the Allied Societies. By late
1918, William J. Gies made plans for publishing
JDR as a journal for dental investigators, and The
Journal of the Allied Dental Societies was discon10S

JADA, Vol. 140

September 2009

tinued and replaced in March 1919 by JDR. JDR

was a quarterly publication and a journal of stomatology; devoted to the advancement and dissemination of knowledge pertaining to the mouth and teeth,
and to their relation to the body as a whole.4 Gies
was listed as the executive officer of JDR and was its
editor from 1919 through 1935. His initiative and
vision spearheaded a significant increase in dental
research, which resulted in JDRs becoming a
bimonthly publication in 1928. In 1934, the journal
became an IADR publication, and, along with many
other journals with a focus on oral health research,
JDR and JADA have served as vehicles for disseminating research findings and explaining the scientific basis of dentistry to the profession. In the latter
part of the 20th century, major biological and medical journals began to publish articles that described
the results of dental and craniofacial research, providing evidence that the science of dentistry had
matured into a discipline that was accepted widely
by the broader scientific community.

American dentistry was recognized widely for its

technical excellence in the first few decades of the
20th century, but it was not known for having a scientific basis. In the early to middle 1920s, a group of
scientists from the University of Vienna were linked
to dentistry in the United States through their participation in Fdration Dentaire Internationale
(FDI) World Dental Federation. They were welcomed into academia in the United States despite
the Great Depression and the resistance of the
National Association of Dental Examiners and most
state dental boards. During this time, dentistry in
the United States was attempting to rise to the challenges and dictates set forth by the Gies report of
1926. The scientists in the Vienna group had biological expertise that complemented the U.S. dentists technical expertise in restorative dentistry,
which helped give the struggling, yet emerging,
dental research effort in the United States a sound
and credible foundation that enabled the profession
to take advantage of the development of IADR and
federal funding of research that would take place
after World War II. Among these immigrants were
Bernhard Gottlieb, Balint Orban, Rudolf Kronfeld,
Harry D. Sicher and Joseph Peter Weinmann.
A turning point occurred in the mid-1920s when
the dean of dentistry at Chicago College of Dental
Surgery at Loyola University, William H.G. Logan,
sought the advice of Bernhard Gottlieb2,9 on how to

ADAF Paffenbarger Research Center

Where many new ideas for dentistry start
or more than 80 years, ADA Foundations
calcium-phosphate bone cements whose use in
Paffenbarger Research Center (PRC) has
humans was approved by the U.S. Food and Drug
played a key role in dentistryidentifying
Administration. More recent developments have
the needs of dental practitioners and translating
included amorphous calcium phosphate, which is
those needs into improved products. Every time
effective in treating sensitive teeth, and remineralyou pick up a front-surface dental mirror or highizing pulp-capping therapies. More than 200 prodspeed handpiece or place a composite restoration
ucts on the market are based on PRC patents. Royor dental sealant, you are taking advantage of
alties from patents are a significant source of
advances developed by scientists at PRC.
revenue for the ADA Foundation, amounting to
Technological breakthroughs at PRC have cre$5.5 million during the past six years.
ated the tools that make modern dentistry posToday, the PRC has a staff of 27 people who
sible, says Dr. Daniel Meyer, senior
work at the NIST campus in Gaithersvice president, American Dental
burg, Md. The scientists at PRC conAssociation (ADA)
tinue to collaborate with NIST
Science/Professional Affairs. Proresearchers on dental product specifijects that are currently under way
cations, as well as new technologies,
will help revolutionize how dental
creating a robust research environdiseases are treated in the future.
ment that has an international repuPRC was established in 1928 as
tation for excellence. The presence of
the Research Unit of the ADA to colwell-equipped laboratories and highly
laborate with the National Bureau
skilled researchers is invaluable to
of Standards (now called the Napracticing dentists when they need
tional Institute of Standards and
timely answers to critical questions.
Technology [NIST]) to develop
For example, earlier this year
science-based specifications for
media reports raised concerns about
Dr. George Paffenbarger
dental products. In 1929, Dr. George
lead in crowns. As soon as the issue
Paffenbarger joined the scientists at the Research
emerged, PRC scientists obtained porcelain powUnit and rapidly became the units lead scientist.
ders from standard commercial sources and finUnder his guidance, the Research Unit continued
ished crowns produced by both domestic and fordeveloping standards to ensure that products pereign dental laboratories. After storing the samples
form predictably, safely and effectively. He also
in an acidic solution, scientists detected no lead in
expanded the scope of Research Unit projects to
the solution, indicating that lead does not leach
further advances in dental materials, equipment
from fired porcelain-fused-to-metal crowns. During
and therapies. In 1985, the ADA renamed the
the process, PRC scientists developed new test
Research Unit in Dr. Paffenbargers honor.
methods that will be useful when questions such
Thanks to his vision, PRC research has resulted
as this arise in the future. PRC researchers also
in technologies that are hallmarks in dentistry:
are looking into other high-profile issues such as
dhigh-speed handpieces;
the risk of developing dental erosion from sports
drhodium-coated front-surface dental mirrors;
drinks and the bioavailability of any bisphenol A
dpanoramic radiography;
that might be present in dental materials.
ddental sealants;
Other PRC projects in the pipeline that promise
dorthodontic bracket bonding;
important rewards for the dental profession
dtooth-colored resin-based composite restorative
danalysis of aerosol production during restorative
ddental bonding adhesives;
procedures or use of ultrasonic scalers and producdcalcium phosphate remineralization.
tion of ultrafine particles during finishing and polIn addition, scientists at PRC developed the first
ishing of resin-based composites;

JADA, Vol. 140

September 2009


dcariostatic delivery devices (chewing gum,

cements, fluoride therapies);
damorphous calcium phosphatecontaining composites that can remineralize tooth structure;
ddental materials that are indistinguishable from
tooth structure;

establish a research endeavor in an academic environment.9 Gottlieb moved to the United States in
1940. He was associated briefly with Columbia University and the University of Michigan, Ann Arbor,
before moving to Baylor University, Dallas, where
he was a professor and the chair of the Department
of Pathology and Research in the School of Dentistry
until his death in 1950.10,11 During his career, Gottlieb wrote numerous scientific articles and four
textbooks and is responsible for founding the study
of oral histology. He has been acknowledged as
being the first dentist to integrate basic science
information with clinical treatment.12
Balint Orban, a protg of Bernhard Gottlieb,
came to the United States from Vienna in 1927 to
establish a research program at the Chicago College
of Dental Surgery at Loyola University. He later
joined the faculty at the University of Illinois College of Dentistry, Chicago. Rudolf Kronfeld was
another protg of Bernhard Gottlieb. His short
career at Loyola University was marked by many
research advancements that helped place science
into the practice of dentistry. His message to clinical
dentists was expressed in an article in which he
delineated the crucial connection between the techniques of restorative dentistry and the biological
foundation on which those techniques rested.13 In
1939, one month before he was to become president
of IADR, Kronfeld died, as his colleague Edgar D.
Coolidge put it, surrounded by his library, his histological material and his work in progress for the
coming season.14
Harry D. Sicher began his career in the United
States at the Chicago Medical College, and then he
moved to the Chicago College of Dental Surgery at
Loyola University. Joseph Peter Weinmann began
his U.S. career in 1938 at the University of Illinois
College of Dentistry, followed by one year at
Columbia University. He then joined the faculty at
the Chicago College of Dental Surgery at Loyola
University. In 1946, he returned to the University of
Illinois. Both scientists undertook significant
research endeavors in oral anatomy, histology, bone
physiology and oral pathology; Weinmann received

JADA, Vol. 140

September 2009

dtissue engineering scaffolds for bone repair.

For more information about PRC and its current
research projects, visit
Anita Mark, manager, Scientific Information, American Dental
Association Division of Science.

significant grant funding from the National Institutes of Health (NIH).9

A tremendous debt is owed to the dentists and
dental scientists who emigrated from Europe to the
United States in the 1930s and 1940s; they were
instrumental in nourishing dental research and
incorporating it into the dental school curriculum.
During this period, Europe was experiencing political upheaval, anti-Semitism and war. Under these
conditions, many dentists and medical scientists
primarily from the University of Viennasought
refuge in the United States. This created a struggle
between the members of the dental profession in the
United States who viewed the emigration of foreigntrained scientists as an opportunity for the dental
profession and as a moral responsibility, and those
who viewed it as an economic threat. Some practicing dentists in Austria and Germany were able to
emigrate to the United States, and some who had
lost their academic positions in Europe received help
from their U.S. colleagues.9 Russell W. Bunting,
then dean of the University of Michigan School of
Dentistry stated that the dental schools making up
the American Association of Dental Schools are
faced with a decision as to what they will do to
orient the stranger dentists within our gates to become useful citizens and respected practitioners.15
The development of oral biology as a discipline
has been an integral factor in Americas contribution
to dental science and practice. Its origins can be
traced back to 1928, when the University of Rochester Medical Center, Rochester, N.Y., established
the first oral biology research and training program
in the United States. The program eventually became the Department of Dental Research in the
School of Medicine and Dentistry. In 1998, the Department of Dental Research (renamed the Center
for Oral Biology) joined five other research centers to
form the Aab Institute of Biomedical Sciences.16
The American Institute of Oral Biology was
founded in 1943 to encourage basic and clinical research for the prevention and treatment of oral disease. It offered practitioners the opportunity to acquire knowledge in allied clinical fields, as well as in


A brief history of the National Institute of Dental Research/National

Institute of Dental and Craniofacial Research and its directors.



H. Trendley Dean


Provided first leadership for dental research at the National Institutes of Health (NIH)
(1931); appointed director of Dental Research Section (1945); became first director of the
National Institute of Dental Research (NIDR) (1948); provided for oversight by the National
Advisory Dental Research Council; awarded first extramural dental research grants and fellowships; supported research on mottled enamel and fluoride, fluorosis, prevention of
dental caries by fluoride and water fluoridation; established intramural research units for
basic and clinical science, created an intramural section for epidemiology and biometry;
advocated for integration of dental health into mainstream medical research.

Francis A. Arnold Jr.


With H. Trendley Dean, led Grand Rapids, Mich., fluoridation study that established water
fluoridation as a safe, effective and economical way to prevent dental caries; established
the first Board of Scientific Counselors to provide advice to the director for intramural
research program; established intramural Laboratory of Biochemistry; provided oversight
for intramural building and laboratory facilities of intramural research program; encouraged dental faculty in the United States to apply for research grants; expanded NIDR
research to dental materials, human genetics and oral medicine; funded first multidisciplinary cleft palate study.

Seymour J. Kreshover


Previously served as the scientific director of the NIDRs intramural research program;
enhanced grants in the neurosciences, pain research, caries prevention through the
National Caries Program (a merger of both intramural and extramural programs) and
craniofacial research and cleft palate reconstruction; enabled the formation of the intramural Laboratory of Oral Medicine, the Laboratory of Microbiology, and expanded
research investments in periodontal diseases, autoimmune diseases and allergic disorders;
expanded intramural research and grants to include pain research and anesthesiology, as
well as the behavioral sciences.

David B. Scott


Expanded extramurally supported research in periodontal diseases, oral and pharyngeal

cancer, and enhanced both intramural and extramural capacity to conduct clinical studies;
stimulated expansion of grants in the behavioral and social sciences; established an intramural Diagnostic Systems Branch to study noninvasive diagnostic techniques; established
an intramural Clinical Investigations and Patient Care Branch to coordinate and integrate
patient treatment with clinical research conducted elsewhere in NIDR and NIH; supported
first consensus development conference on dental implants.

Harald Le


Established the Epidemiology and Oral Disease Prevention Program to include periodontal
and other diseases of the oral cavity; established the Dentist Scientist Award program to
enhance clinical research; expanded extramural dental research to include research centers
in the collective fields of oral biology, oral and craniofacial diseases and disorders, and
minority oral health; initiated first national surveys of U.S. adult oral health and childrens
caries; initiated programs of continuing dental education and public information to translate research findings; established World Health Organization Collaborating Center for
Dental Research and Training.

Harold C. Slavkin


Engineered renaming NIDR as National Institute of Dental and Craniofacial Research

(NIDCR) to reflect expanded research mission; promoted research in developmental
biology, genetics, oral complications of HIV/AIDS, and oral health needs of minority and
vulnerable populations; encouraged scientists outside of dentistry to focus on the structure and function of the oral and craniofacial area; reached out to the dental profession,
patient groups and the public to promote communication of NIDCR research findings;
facilitated NIDCR leadership in Oral Health in America: A Report of the Surgeon General*
the first of its kind dedicated solely to oral health.


Increased support for research on oral health disparities, neuroscience of chronic pain,
head and neck cancer, Phase III clinical trials, genomics (including genome-wide association studies), systems biology of salivary glands and diagnostic potential of saliva; supported creation of a dental practice-based research network and a formal Dentist Scientist
Training Program for concomitant Doctor of Dental Surgery/Doctor of Philosophy degree
training; fostered interdisciplinary research as cochair of the NIH Roadmap program on
Research Teams of the Future; helped lead NIH initiative to enhance peer review; served as
acting deputy director of NIH (November 2008-spring 2009).

Lawrence A. Tabak

* Source: U.S. Department of Health and Human Services.19

fields traditionally associated with dentistry. It also

served as a meeting ground for academically oriented researchers and clinicians. In 1959, IADR and the
ADA sponsored the First International Conference
on Oral Biology (with a grant from the Colgate-

Palmolive Company, New York City) and the proceedings were published in JDR.17 The journal
Archives of Oral Biology began publication the same
year. In 1988, the first step was taken to form a
society of oral biologists as part of a section of the
JADA, Vol. 140

September 2009


highlights the directors and history of NIDCR.

The U.S. governments funding
of oral health research can be
traced back many years. In 1916,
President Woodrow Wilson created the National Research
Council of the National Academy
of Sciences to coordinate the
nations scientific research facilities for defense work. It was one
of the first federal governmental
bodies to promote dental biological research.3 In 1918, a division
of medical sciences was created,
and, in 1919, a committee chaired
by Thomas B. Hartzell from the
University of Minnesota was
formed to encourage scientific
President Harry S. Truman signs the bill establishing the National Institute of Dental Research,
June 24, 1948. Also present (from left): Dr. C. Willard Camalier, director, Washington office of
research in dentistry; however, it
the American Dental Association; Congressman Walter E. Brehm (Ohio), author of the bill; Dr.
faced many roadblocks including
H.B. Washburn, ADA president; Dr. Bruce D. Forsyth, chief dental officer, Public Health Service;
Dr. Carl O. Flagstad, chairman, ADA Committee on Legislation; Dr. Daniel F. Lynch, past presilack of financial support. A breakdent, District of Columbia Dental Society; and Dr. H. Trendley Dean, dental director, National
through occurred in 1924, howInstitutes of Health.
ever, when the Carnegie CorporaAmerican Association for Dental Research. This
tion, New York City, a member of the National
organization became the American Association of
Research Council of the National Academy of SciOral Biologists, and its first annual meeting was
ences, awarded $85,000 to the University of Caliin 1989.
fornia College of Dentistry in San Francisco to
undertake, through cooperation of a number of men
in different fields of science, a joint study of pyorrhea
and its possible relation to other human maladies. 20
The ADA Scientific Foundation and Research ComFUNDING OF ORAL HEALTH RESEARCH
mission helped plan the project, and the award
Overall, the major driver of Americas contribution
marked the first large dental research grant in the
to the science of dental practice and oral health has
United States from a foundation outside the dental
been the National Institute of Dental and Craniofacommunity.21
cial Research (NIDCR)known as the National InThe NIH originated in 1887 in Staten Island,
stitute of Dental Research (NIDR) until Oct. 21,
N.Y., as a small laboratory called the Laboratory of
1998. The institute was founded in 1948 and has
Hygiene in the Marine Hospital Service, a precursor
stimulated and funded many of the scientific adto the U.S. Public Health Service. In 1891, the Hyvances in dentistry and dental practice. Directed by
gienic Laboratory, as the small laboratory became
visionary dental scientists, NIDCR has been instruknown as, moved to Washington, and, in 1930, the
mental in transforming dentistry from a technical
Ransdell Act changed the name of the Hygienic Labprofession to one that is based firmly in prevention
oratory to the National Institute of Health and
and technological innovation.18 NIDCR-supported
established research fellowships to investigate basic
research has had a major impact on public health,
biological and medical problems. In July 1930, the
dental practice and our understanding of dental and
ADA passed a resolution that requested the U.S.
craniofacial function and disorders. It has played a
surgeon general to conduct dental research.22
critical role in many areas of public health and denIn 1948, largely through the efforts of the ADA
tal practice, such as caries and water fluoridation,
with support from IADR, President Harry S. Trudental sealants, composite restorations, acid-etch
man signed legislation that established NIDR, now
bonding, periodontal disease and therapy, oral canNIDCR.20 NIDR was one of the first of the 27 NIH
cer, pain control, and salivary function. The table
institutes and centers to be established. Much of the

JADA, Vol. 140

September 2009

impetus for this legislation was that during World

War II many young American men could not serve
in the military because they did not have the minimum number of six opposing teeth required to
qualify for combat.20 Fluoridation was the first challenge faced by the leaders of the fledgling institute,
and the need to train dental researchers was critical.
By 1972, NIDR had supported more than 1,600
trainees and fellows, most of whom were involved in
teaching and research and more than one-half of
whom were involved in providing patient care.20

In the late 20th century, and continuing now,

evidence-based practice, bioinformatics and biomimetics emerged and promise to have a major
impact on the future of dental practice. Evidencebased practice is the process of integrating clinically
relevant scientific evidence with the patients oral
and medical conditions and histories, the dentists
clinical expertise, and the patients treatment needs
and preferences.23 Dental bioinformatics has been
defined as the application of computer and informational sciences to improve dental practice, research,
education and professional management,24 and it
will play an increasingly important role in the way
dentistry is practiced in the future. For example,
bioinformatics will facilitate the discovery of more
sensitive and specific drugs for the treatment and
management of diseases and disorders, and it will
enable dental and medical records to be accessed
readily anywhere in the world. Biomimetics is the
study of the structure and function of biological systems as models for the design and engineering of
materials and machines. While biomimetics has had
a place in dentistry for many years in developing
dental materials, it promises to take on new importance in terms of tissue engineering and the development of true biological biomaterials to replace
body parts such as teeth, salivary glands, muscle,
cartilage, bones and joints.25 Taken together, these
relatively new disciplines hold great promise for the
future of dental education and clinical practice and,
ultimately, for the improvement of oral and craniofacial health.

In the last 150 years, dentistry has faced many challenges as it has moved from a purely technical profession to one that is increasingly science-based. The

future must be driven by a global vision for the provision of science-driven oral health care and the commitment of dental educators and practitioners to embrace science as an integral part of our profession.
Disclosure. Dr. Gutmann did not report any relevant disclosures.
1. Gies WJ. Dental Education in the United States and Canada: A Report
to the Carnegie Foundation for the Advancement of Teaching. New York
City: The Carnegie Foundation for the Advancement of Teaching; 1926.
2. Lesky E. The Vienna Medical School of the 19th Century. Baltimore:
Johns Hopkins University Press; 1976.
3. Lufkin AW. A History of Dentistry. Philadelphia: Lea & Febiger; 1938.
4. International Association for Dental Research. The First Fifty-Year
History of the International Association for Dental Research. Chicago:
University of Chicago Printing Department; 1973.
5. Prinz H. Dental Chronology: A Record of the More Important Historic
Events in the Evolution of Dentistry. Philadelphia: Lea & Febiger; 1945.
6. Thompson AH. Scientific methods in practice. Dent Cosmos 1884;26(8):
7. Miller WD. The Micro-Organisms of the Human Mouth: The Local and
General Diseases Which Are Caused by Them. Basel, Switzerland: S.
Karger; 1973.
8. Orland FJ. William John Gies: His Contributions to the Advancement
of Dentistry. New York City: The William J. Gies Foundation for the
Advancement of Dentistry; 1992.
9. Kremenak NW, Squier CA. Pioneers in oral biology: the migrations of
Gottlieb, Kronfeld, Orban, Weinmann, and Sicher from Vienna to America.
Crit Rev Oral Biol Med 1997;8(2):108-128.
10. Ornish N. Pioneer Jewish Texans: Their Impact on Texas and
American History for Four Hundred Years, 1590-1990. Dallas: Texas Heritage Press; 1989.
11. Ornish N. Gottlieb, Bernhard. The Handbook of Texas Online. Accessed
July 9, 2009.
12. Davis WL, Jones RG. A new look at the Gottlieb collection: the continuing evaluation of the Gottleib collection reveals new and significant scientific information. Baylor Dent J 1985;29:22-29.
13. Kronfeld R. Research and the future of dentistry. Bull Chicago Dent
Soc 1939;19:17.
14. Coolidge ED. Rudolf Kronfeld, BS, MD, DDS. J Dent Res 1943;19:
15. Bunting RW. The educational problem presented by the refugee dentist from Europe. In: Proceedings of the Sixteenth Annual Meeting of the
American Association of Dental Schools Held at Cleveland, Ohio, March
Twenty-First, Twenty-Second and Twenty-Third, Nineteen-Hundred and
Thirty-Nine. Indianapolis: American Association of Dental Schools; 1939:
16. Goldsmith LA, Tabak LA, Stein JH. Aab Institute of Biomedical Sciences. Mol Med 1999;5(10):645-653.
17. Williams NB, Robinson HGB. First International Conference on Oral
Biology: abstracts of papers presented. J Dent Res 1960;39:1083-1097.
18. Pihlstrom BL, Tabak L. The National Institute of Dental and Craniofacial Research: research for the practicing dentist. JADA 2005;136(6):
19. U.S. Department of Health and Human Services. Oral Health in
America: A Report of the Surgeon General. Rockville, Md.: U.S. Department of Health and Human Services, National Institutes of Health,
National Institute of Dental and Craniofacial Research; 2000. NIH publication 00-4713.
20. Harris RR. Dental Science in a New Age: A History of the National
Institute of Dental Research. Rockville, Md.: Montrose Press; 1989.
21. Annual report of the secretary-treasurer of the Scientific Foundation
and Research Commission of the American Dental Association from July 1,
1923, to June 30, 1924. Transactions 1924:182-183.
22. Report of the American Dental Association Commission on Dental
Legislation to the National Institutes of Health. Transactions 1930:160.
23. Ismail AI, Bader JD; ADA Council on Scientific Affairs and Division
of Science; Journal of the American Dental Association. Evidence-based
dentistry in clinical practice. JADA 2004;135(1):78-83.
24. Schleyer T, Spallek H. Dental informatics: a cornerstone of dental
practice. JADA 2001;132(5):605-613.
25. Slavkin HC. Building sound and regular teeth: the National Institute
of Dental Research celebrates its golden anniversary. JADA 1998;129(6):

JADA, Vol. 140

September 2009


Science is the fuel for the engine

of technology and clinical practice
Malcolm L. Snead, DDS, PhD; Harold C. Slavkin, DDS

cience is the fuel for the

engine of technology and
clinical practice. How do
we formulate a diagnosis
and prognosis? What are
the ways of treating the diseases
and disorders that challenge the
human condition? Is one outcome
better than another? The answers to
these questions come from our sustained investment in the science
that fuels our educational system.
Bright minds exposed to questions
such as these have created and will
continue to create technology that
improves patient care.
We think of the Scientific Revolution of the 16th and 17th centuries
as the intellectual and technological
movement that shaped the modern
world. Yet, today we live in another
time of scientific revolution, characterized by great speed and enormous accomplishment in the chemical, physical and biological realms
of inquiryfrom discovery to application. In the 20th century, scientists identified the structure and
function of DNA and applied it to
cellular and molecular biology to
better understand the microbial
and human ecosystems and their
The scientific disciplines in the
21st century are being shaped by

Background. The biological, chemical, behavioral and physical sciences provide the fuel for innovation, discovery and technology that continuously improves the quality of the human condition. Computer power
derived from the dramatic breakthroughs of the digital revolution has
made extraordinary computational capacity available for diagnostic
imaging, bioinformatics (the science of information) and numerous
aspects of how we practice dentistry in the 21st century.
Overview. The biological revolution was initiated by the identification
of the structure for DNA in 1953, a discovery that continues to catalyze
improvements in patient care through new and better diagnostics, treatments and biomaterials. Humanitys most basic and recognizable characteristicsincluding the faceare now better understood through the elucidation of our genome and proteome, the genes and proteins they encode.
Health care providers are beginning to use personalized medicine that
is based on a persons genetic makeup and predispositions to disease
Conclusions. Advances in the fields of genetics, developmental and
stem cell biology, and many other disciplines continue to fuel innovative
research findings that form the basis for new diagnostic tests, therapeutic
interventions and procedures that improve the quality of life for patients.
Scientists are on the threshold of applying knowledge in stem cell biology
to regenerative medicine and dentistry, heralding an era when clinicians
can consider using biological engineering to replace tissues and organs
lost to disease or trauma.
Key Words. Discovery; molecular biology; chairside application.
JADA 2009;140(9 suppl):17S-24S.
Dr. Snead is a professor, Center for Craniofacial Molecular Biology, School of Dentistry, The University
of Southern California, 2250 Alcazar St., Los Angeles, Calif. 90033, e-mail
Address reprint requests to Dr. Snead.
Dr. Slavkin is a professor, Center for Craniofacial Molecular Biology, School of Dentistry, The University
of Southern California, Los Angeles.

JADA, Vol. 140

September 2009


the merging of biology, genetics, engineering and

computational sciences to create discoveries at the
interfaces of these disciplines. When combined with
the key ingredient of well-trained clinicians, this
merger has resulted in remarkable strides in our
understanding of disease and allows for more rapid
advances, particularly at the molecular level. Even
more so than in the past, dentistry will rely on science to create new diagnostic tests and therapies to
improve patient care.5-10 Optimizing care for
patients must be our goal.
In this all-too-brief review, we highlight a few
select examples of discoveries, drawn from the last
50 to 60 years, to celebrate the 150th anniversary
of the American Dental Association (ADA). Readers
should appreciate that this review is but a small
sampler of the incredible scientific advances that
have shaped what we know, how we think and how
we practice clinical dentistry in the dawn of the
21st century. We have attempted to do this by
focusing on specific themes and ideas to highlight
prominent scientific discoveries and attainment of
knowledge that have had an impact on patient
care. Science knows no geopolitical boundaries and
we recognize the profound contributions of scientists working in other countries. However, because
this supplement commemorates the 150th anniversary of the ADA, we have concentrated on the scientific contributions of scientists who have worked
in the United States.

The engine of science has contributed to significant

advances by mapping and deciphering the
nucleotide letters of the human genome and by
describing the proteome, the information that comprises all the genes and their encoded proteins that
make us human. This has resulted in remarkably
precise diagnostic tests and rapid improvements in
patient treatment. One of the most extraordinary
scientific discoveries of the 20th century was elucidating the structure and possible functions of DNA
(see illustration11). Significantly, it was a dentist,
Norman Simmons, who first isolated sufficiently
pure DNA in 1952 (see photograph12); Rosalind
Franklin then created the first x-ray crystallography images from that DNA. These images led
James Watson, Francis Crick and Maurice Wilkins
to predict the structure of DNA in 1953.1 In
Wilkins acceptance speech for the Nobel Prize in
Physiology or Medicine in 1962, he credited
Norman Simmons for having refined techniques of
isolating DNA and thereby helping a great many

JADA, Vol. 140

September 2009

workers, including ourselves.13

Norman Simmons received a bachelors degree in
science in 1935 from the City College of New York,
New York City; a Doctor of Dental Medicine degree
in 1939 from Harvard, Boston; and a Doctor of Philosophy degree in 1950 from the University of
Rochester, Rochester, N.Y. His doctoral thesis was
titled Investigation of Submaxillary Mucoid and
the Defense Mechanisms of the Mouth.14
Simmons was nominated for the Nobel Prize in
Physiology or Medicine in 1972 in recognition of his
fundamental studies of changes in light absorption
associated with conformational changes within proteins and polypeptides: the so-called Cotton
effects (named after Aim Cotton). These studies
led him to explore the structure of viral particles.15
Thereafter, his fundamental scientific work in
nuclear medicine and oral biology at the University
of California, Los Angeles (UCLA), as well as his
studies of the isolation of tobacco mosaic virus
DNA and RNA, served as the foundation that led to
the development of numerous nucleic acid and
polypeptide biomarkers for disease diagnostics.
Robert Gorlin earned a bachelors degree from
Columbia University, New York City, and a dental
degree in 1947 from Washington University School
of Dentistry, St. Louis. He then made the University of Minnesota School of Dentistry, Minneapolis,
his home base for the second half of the 20th century. Gorlin was widely known for his ability to
deftly integrate his encyclopedic knowledge of craniofacial birth defects with clinical observation,
phenotypic traits and specific genotypes. One of
Gorlins contributions was the ability to discriminate between syndromic and nonsyndromic birth
defects. His memory of craniofacial anomalies was
almost as extraordinary as was his clinical
prowess; both dentists and physicians consulted
him for his diagnostic expertise. Gorlins diagnostic
skills became known internationally through his
lectures, book chapters, books and peer-reviewed
publications.16 From esoteric to mainstream diseases and disorders, he was considered an expert in
diagnosing craniofacial-oral-dental birth defects.
The key to his success was his ability to see, to
understand and to integrate an array of seemingly
disparate information: he saw the system of the

ABBREVIATION KEY. BMP: Bone morphogenetic protein. NIDCR: National Institute of Dental and Craniofacial Research. 3-D: Three-dimensional. UCLA: University
of California, Los Angeles.

DNA is a double helix formed by base pairs attached to a sugar

phosphate backbone. Reprinted from the U.S. National Library of
Medicine, National Institutes of Health, Bethesda, Md.11

Dr. Norman Simmons. Reproduced with permission of the University

of Rochester Medical Center, Rochester, N.Y.12

body when others saw only derangements of its

parts. Gorlin became one of the leading geneticists
in the world and was the recipient of numerous
awards, including the Award for Excellence in
Human Genetics Education from the American
Society for Human Genetics.17
By the end of the 20th century, researchers had
begun to identify the specific role of genes in
various oral diseases; this was, in no small measure, the result of the remarkable sensitivity and
specificity derived from molecular biology for applications to clinical dentistry. For example, we have
learned that Papillon-Lefvre syndrome, an autosomal recessive disorder characterized by periodontal disease and palmoplantar keratosis and
diagnosed mainly by dentists, is caused by a mutation in the cathepsin C gene.18,19
Another scientific discovery was the isolation,
characterization and clinical application of the
major gene for enamel formation: amelogenin. The
collaboration of an interdisciplinary team from
Baylor College of Medicine, Houston, and the University of Southern California, Los Angeles,
enabled the first dental gene to be cloned.20 Isolation of this gene to the X and Y chromosomes21 provided a forensic tool to discriminate the corporal
remains of males versus females and provided the

basis for advancing our understanding of the

Mendelian inheritance of enamel birth defects.22
Another major advance in dental genetics was
the discovery that a gene on chromosome 4 generates three gene products: dentin phosphoprotein,
dentin sialoprotein and dentin glycoprotein.23,24 The
molecular cloning and mapping of the gene for
ameloblastin, the second most abundant enamelforming protein, also was accomplished.25 Furthermore, investigators have linked the human genome
and proteome at the level of teeth, extending our
understanding of normal and abnormal formation
of the dentin and enamel tissues.26
Another use of genetic science is somatic cell
gene therapy to treat human disease. Researchers
at the National Institute of Dental and Craniofacial Research (NIDCR) are moving genes from the
laboratory to chairside to treat salivary gland diseases.27 It also may be possible to transfer genes to
readily accessible salivary glands and use them as
biofactories or as a source of proteins to treat diseases caused by deficient protein biosynthesis. As
dentists, we appreciate that the mouth is readily
accessible and that its tissues may provide a relatively easy route for introducing genes to prevent
or treat a variety of oral and other diseases. The
future holds great promise that researchers will
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September 2009


identify the genetic basis of many diseases so that

clinicians can provide specific preventive care and
treatment to patients through somatic cell gene
transfer therapy.

We have come a long way since osteoblasts first

appeared in primitive bony fish (the ostracoderms).
During this evolution, a bony armor formed around
the head, leaving cavities for the organs of sight,
smell and hearing and, of course, the brain. Eventually, 22 bones evolved to articulate and form the
craniofacial-oral-dental complex. Bone has an
essential role in supporting the teeth during mastication, but age, disease, trauma and birth defects
all serve to remove bone. Today, our clinical challenge is to devise a strategy to generate bone to correct birth defects or to replace bone lost as a result
of injury or disease.
In the 1960s, researchers observed that histiocytes were transformed into osteocytes by autoinduction, a process in which explanted bone induced
new bone formation, often with hematopoietic bone
marrow.28,29 Huggins30 showed the capacity of the
urinary bladder to induce new bone formation
when it came into contact with abdominal muscle
cells, and Reddi and Huggins31 described the biochemical sequences in the transformation of
normal fibroblasts into bone cells. The extractable
protein that induced new bone was termed bone
morphogenetic protein (BMP),32 and researchers
used recombinant DNA technology to identify a
complementary DNA clone for one of the BMPs,
which allowed the new technology to produce therapeutic amounts of the protein.33 The commercial
availability of BMPs helped us understand how
they work so that we can harness their healing
powers. Overall, this research allowed this otherwise scarce protein to be manufactured in the laboratory for use at chairside and bedside.34,35
Efforts to examine the ability of dentin to induce
bone led researchers to identify a small-molecularweight protein isolated from dentin that induced
naive cells to form cartilage and bone. Rather than
a newly discovered BMP, the isolated protein is a
small amelogenin protein that researchers previously thought was involved only in enamel matrix
The recovery of enamel matrix proteins, mainly
amelogenin protein, led to the production of a com20S

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September 2009

mercial gel that can induce progenitor cells to

regenerate bone and cementum in the treatment of
periodontal disease.39 Clinicians now use enamel
matrix proteins and/or BMPs to recruit and direct
resident stem cells to regenerate lost tissues such
as periodontal ligament, acellular cementum and
alveolar bone. The study of enamel matrix proteins,
such as amelogenin, is continuing in the hope of
discovering how they alter cells and direct their differentiation to form bone and cementum while
attenuating the inflammatory response.40,41
Investigators working at NIDCR recovered stem
cells from human primary teeth, a site that was not
known previously to contain such cells.42 In a large
collaborative effort that reflects the intense research
needed for progress in this field, researchers used
stem cells in pigs to engineer a functioning cellmediated root replacement, complete with a periodontal ligament.43 Researchers also have shown
that periodontal ligament stem cells,44 as well as
other sources of stem cells, modulate the immune
response, offering hope for patients with autoimmune diseases such as lupus erythematosus that a
new therapeutic tool can be developed.45
Scientists are investigating the use of implantsupported distraction osteogenesis that will prove
useful for bone regeneration in craniofacial reconstruction.46 They have shown that a unique population of cells with stemlike qualities, known as the
neural crest, responds to signals provided by
members of the transforming growth factor family
of molecules. The neural crest cells participate in
forming the bones of the head and face, as well as
contribute to the sutures that permit growth of the
skull, while errors in cell signaling can result in
developmental birth defects.47,48 Collectively, this
research provides insight into the molecular mechanisms that may cause craniofacial anomalies and
offers great promise regarding treatment that can
improve quality of life for affected patients.49

Previous achievements in science have fueled the

creative advances in technology in the 20th century. In 1895, Roentgen accidentally discovered
that human bones could be imaged, and that the
images could be used for dental or medical diagnostics, resulting in the first opportunity to see inside
the body without creating a surgical wound.50 Otto
Walkhoff, a dentist, obtained the first radiograph
of the jaw just weeks after Roentgens discovery.51
A remarkable dentist, C. Edmund Kells used radiography, as well as fitted his dental operatory with

electric equipment, compressed air and suction;

these items, although improved, are still in use
After World War II, Robert Ledley, a dentist and
graduate of New York University, New York City,
who worked at the precursor to the National Institute of Dental Research, revolutionized how we
know what we see.55,56 Ledley pioneered computerized tomographic scanning in the early 1950s. He
took the scientific discovery of x-rays to a new level
of understanding. His inventions, hardware and
algorithms for software introduced a threedimensional (3-D) approach by which x-rays were
transmitted through varying tissue densities to
capture 2-D and 3-D images of all parts of the
human anatomy. This remarkable achievement
was the precursor of modern diagnostic imaging
used in both dentistry and medicine.

Remarkable scientific advances have been made in

tissue repair, wound healing and tissue regeneration owing to, in no small part, the genius of Russell Ross, a dentist who had a distinguished career
in pathology. He served for many years as the chair
of the Department of Pathology, University of
Washington School of Medicine, Seattle.
Using transmission electron microscopy, a novel
animal model of parabiotic mice, radiology and an
exquisite knowledge of the early advances in
wound immunology and pathology, Ross synthesized the essence of wound healing. In publications
dating to the 1960s, he defined the timing, cytology, physiology, immunology and connective-tissue
biochemistry of wound healing.57,58 His strategy of
using parabiotic mice enabled his team to trace cell
origins and cell fate during various stages of wound
healing. Simply stated, Ross team provided the
foundation for our modern understanding of wound
During the early 1970s, Ross and his team proposed that localized injury to the lining of the arterial wall was responsible for the unusual accumulation of smooth muscle cells within the wall of the
artery, thereby reducing the lumen of the vessel.59
Ross used interdisciplinary scientific inquiry to
study the problem of atherosclerosis. His team discovered a new growth factor called plateletderived growth factor that stimulates proliferation
of smooth muscle cells.60,61 Curiously, these accumulated smooth muscle cells contain elaborate
secretory vesicles that are filled with several types

Dr. Robert Ledley. Courtesy of National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md.

of collagen, fibronectin, metalloproteinases, proteoglycans and fatty acids that assemble into an abundant extracellular matrix associated with atherosclerosis. Ross62,63 concluded that atherosclerosis is
an inflammatory disease. These contributions are
examples of how scientific advances in improving
the human condition were derived from the passion
and creativity of people who began their careers in

Tissue destruction was another focus of attention

for dental scientists. Their efforts to understand
tissue loss associated with periodontal disease led
to significant advances in our understanding of
enzymatic degradation of collagen, with the work of
Fullmer and Gibson64 revealing that collagenase is
present in the tissues of the human host. This
research had far-reaching consequences for other
investigators working to understand the destructive process brought about by inflammation. Investigators identified a new class of metal-containing
enzymes, the metalloproteinases, along with their
endogenous inhibitory counterparts, that formed a
yin and yang for homeostasis. These studies have
had an impact in many areas of biomedical sciences,
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September 2009


helping us understand such phenomena as cancer

cell metastasis and angiogenesis, as well as the
degradation of enamel matrix proteins during
enamel biomineralization.65-67 Knowledge about the
destructive effects of inflammation also led to U.S.
Food and Drug Administration approval and clinical use of collagenase-inhibiting low-dose doxycycline in the treatment of periodontal disease.68 In
addition, studies of the metabolism of the extracellular matrix led to the formulation of an artificial
basement membrane, which allowed cells to be
maintained in a 3-D architecture that resembled
native tissue.69

Saliva is emerging as an exciting diagnostic tool for

dentists and physicians. For example, dental scientists at UCLA are investigating saliva as an aid in
the diagnosis of oral cancer.70 Many dentists have
provided the foundation for using saliva as a diagnostic fluid. Dating back to at least 1960, Irwin
Mandel of the School of Dental and Oral Surgery at
Columbia University recognized the potential of
saliva as an informative body fluid.71,72 His passion to understand saliva was infectious and
attracted many dental scientists to this field of
inquiry. Mandels contributions to science opened
up opportunities in many areas of biomedical scientific research and clinical practice with regard to
the diagnosis of disease or monitoring the progression of disease or treatment by using salivary biomarkers. Mandel asserted that saliva, like blood
and urine, provided informative clues about health
and disease. His basic work in saliva sampling and
analysis provided the framework for many contemporary salivary studies.
In the mid-1960s, dental scientists found that
viral particles can be secreted through the salivary
glands, thus connecting general health with the
oral cavity.73 Later, Oppenheim and colleagues74
identified the molecular basis of the beneficial
effects of saliva on the oral cavity by identifying
antimicrobial properties of various salivary proteins; others provided the foundation for the use of
enamel remineralization to control caries by identifying salivary proteins that modulate the maintenance of salivary calcium and phosphorous.75,76
Other investigators77,78 have been instrumental in
characterizing the salivary proteome (that is, all of
the proteins produced by the salivary gland); in
doing so, they laid a foundation for the use of saliva
as a diagnostic fluid, because it contains not only
salivary proteins, but also proteins from other

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September 2009

organs that can be used as surrogate markers for a

variety of disease states.
While working at the University at Buffalo, The
State University of New York, Michael Levine
spawned several important discoveries regarding
salivary proteins.79 Levine and his colleagues identified the importance of salivary proteins as part of
the framework for bacterial adherence to the teeth
via bacterial proteins that interact with specific
domains within salivary proteins, forming a molecular fastener similar to Velcro.80 Other dental scientists who began their careers at the University
at Buffalo contributed to our understanding of
streptococci in the aggregation of human platelets
and virulence factors associated with bacterial
Bacterial biofilms are inherently resistant to
antimicrobial agents and are associated with many
infections, including caries and periodontal
disease.83 However, investigators have shown that
protective immunity to caries may be achieved by
ingestion of Streptococcus mutans, which can
induce secretion of salivary immunoglobulin A.84
These findings led other investigators to explore
the possibility of producing a human vaccine to
streptococci, an organism associated with dental
caries, the most common infection of mankind.85,86

Dental science in the 20th century evolved from the

crucible of William J. Gies, a biochemist at
Columbia University who convinced the Carnegie
Foundation to support an analysis of dental science
and education in the United States, aligned with
the foundations previous support of Flexner and
Pritchetts5 analyses for medicine. The Gies report
was published in 1926, and it heralded a new age
in American dentistry that would have a foundation in the biological, chemical and physical sciences, as found in major academic health science
In 1948, leaders of the ADA helped establish a
dental institute within the National Institutes of
Health in Bethesda, Md. The interdisciplinary
work of so-called dental research blossomed and
became the beacon of dental science for the world.
The first major scientific achievement of the fledgling dental institute was the use of fluoridation to
prevent caries, made possible by H. Trendley Dean
(first director of the then National Institute of
Dental Research).87 Thereafter, the institute
focused on fundamental research in many areas,
such as oral microbiology and immunology, human

craniofacial-oral-dental genetics, salivary glands

and saliva, connective-tissue biochemistry, bone
biology, craniofacial biology, microbial genomics
and proteomics, oral neoplasia, and biobehavior
and pain, as well as international outreach.
One essential mission of NIDCR is making scientific training available for oral health professionals, people who continue to acquire new
knowledge and make discoveries and develop applications, thereby shaping what is thought and
taught in our profession. Through the years, it has
nurtured many scientists and clinicians to improve
the health of Americans. The surgeon generals
report on Americas oral health in 2000 marked the
new millennium by emphasizing that good general
health must include good oral health,88,89 a mission
we celebrate on the 150th anniversary of the ADA.

Advances in the fields of genetics, developmental

and stem cell biology, and many other disciplines
continue to fuel innovative research findings that
form the basis for new diagnostic tests, therapeutic
interventions and procedures that improve patients quality of life. Scientists are on the
threshold of applying knowledge in stem cell
biology to regenerative medicine and dentistry,
enabling clinicians to consider using biological
engineering to replace tissues and organs lost to
disease or trauma.
Disclosure. Drs. Snead and Slavkin did not report any disclosures.
The authors thank their colleagues for the many stimulating conversations and manuscripts that formed the foundation of this brief review.
They apologize for the exclusions required by space considerations. They
note the passion that investigators bring to their work, that they share
with their colleagues and that they instill in their students. Their traits
assure us that the next century will be filled with discoveries and innovation that will improve the care of our patients.
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The biology, prevention, diagnosis

and treatment of dental caries
Scientific advances in the United States
Domenick T. Zero, DDS, MS; Margherita Fontana, DDS, PhD;
E. Angeles Martnez-Mier, DDS, MSD, PhD; Andra Ferreira-Zandon, DDS, MSD, PhD;
Masatoshi Ando, DDS, PhD; Carlos Gonzlez-Cabezas, DDS, MSD, PhD; Stephen Bayne, MS, PhD

ental scientists living

and working in the
United States during
the last 50 to 60 years
have contributed to our
understanding that dental caries is
a chronic, dietomicrobial, sitespecific disease caused by shifts
from protective factors favoring
tooth remineralization to destructive factors leading to demineralization. We now know that caries
results from complex interactions
among the tooth structure, the
dental biofilm, and dietary, salivary and genetic influences. The
distribution of caries has changed
in the last century. Relatively
recent data indicate that about 90
percent of carious lesions occur in
the pits and fissures of permanent
posterior teeth and that molar
teeth are most susceptible to
caries.1 The disease is unequally
distributed in the U.S. population;
people who are minorities, homeless, migrants, children with disabilities and of lower socioeconomic
status have the highest prevalence
and severity of caries.1 This article
briefly outlines major scientific
advances in cariologywith, in
honor of the 150th anniversary of
the American Dental Association
(ADA), an emphasis on contributions made by those living and
working in the United States.

Background. Scientific advances in cariology in the past 150 years
have led to the understanding that dental caries is a chronic, dietomicrobial, site-specific disease caused by a shift from protective factors favoring
tooth remineralization to destructive factors leading to demineralization.
Epidemiologic data indicate that caries has changed in the last century; it
now is distributed unequally in the U.S. population. People who are
minorities, homeless, migrants, children with disabilities and of lower
socioeconomic status suffer from the highest prevalence and severity of
dental caries.
Results. Scientific advances have led to improvements in the prevention, diagnosis and treatment of dental caries, but there is a need for new
diagnostic tools and treatment methods.
Conclusions and Clinical Implications. Future management of
dental caries requires early detection and risk assessment if the profession is to achieve timely and cost-effective prevention and treatment for
those who need it most. Dental professionals look forward to the day
when people of all ages and backgrounds view dental caries as a disease
of the past.
Key Words. Caries; remineralization; saliva.
JADA 2009;140(9 suppl):25S-34S.
Dr. Zero is the associate dean for research, a professor and the chair, Department of Preventive and
Community Dentistry, and the director, Oral Health Research Institute, Indiana University School of
Dentistry, 415 Lansing St., Indianapolis, Ind. 46202-2876, e-mail Address reprint
requests to Dr. Zero.
Dr. Fontana is an associate professor and the director, predoctoral education, Department of Preventive
and Community Dentistry, School of Dentistry, and the director, Microbial Caries Facility, Oral Health
Research Institute, Indiana University School of Dentistry, Indianapolis.
Dr. Martnez-Mier is an associate professor and the director, the Fluoride Research Program, Department of Preventive and Community Dentistry, Indiana University School of Dentistry, Indianapolis.
Dr. Ferreira-Zandon is an associate professor and the director, Early Caries Detection Program, Department of Preventive and Community Dentistry, Indiana University School of Dentistry, Indianapolis.
Dr. Ando is an assistant professor, Department of Preventive and Community Dentistry, Indiana University School of Dentistry, Indianapolis.
Dr. Gonzlez-Cabezas is an associate professor and the director, Secondary Caries Program; director,
Graduate Education, Department of Preventive and Community Dentistry; and director, Laboratory
Research Facility, Oral Health Research Institute, Indiana University School of Dentistry, Indianapolis.
Dr. Bayne is a professor and the chair, Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor.

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September 2009



Microbial etiology. Willoughby Miller,2 a dentist

and early dental researcher, proposed that oral
bacteria in the presence of fermentable carbohydrates produced acids that dissolved tooth structure. Together with research on plaque by William3
and Black,4 this concept evolved as the foundation
for our current knowledge of caries etiology. However, early caries investigators did not understand
the specific nature of the bacterial infection contributing to caries and that restorative strategies
alone, such as extension for prevention,5 were not
successful in controlling the disease. Thus, dentists
dealt mainly with the continuing sequelae of this
widespread disease during the first half of the
20th century.6
Throughout the 20th century, of all possible etiological organisms associated with dental caries, the
mutans streptococci (MS) group captured the
greatest interest. Researchers initially isolated
Streptococcus mutans from human carious lesions,7
but it was not until much later, when researchers
conducted animal studies, that the bacterial etiology of dental caries was established firmly.8,9
Children acquire some oral microorganisms, such
as S. mutans, from their mothers or primary caregivers early in life.10 Therefore, caries is a microbial
disease in which etiologic bacteria are normal constituents of the oral microbiota that cause disease
only when their proportions and pathogenicity
change in response to environmental conditions.11
The key caries-associated microbial virulence traits
include acidogenesis and acid tolerance,12 intracellular polysaccharide storage13 and extracellular
glucan formation, which promotes MS attachment14
and increases plaques pH-lowering ability.15,16
Although S. mutans is one of the most researched
cariogenic microorganisms, it is only one of more
than 500 species found in dental plaque.17 In
studies using molecular identification of bacteria,
investigators have reported that diverse bacterial
communities, including some novel species, are
associated with dental caries and that S. mutans is
not detectable in 10 to 20 percent of people who
have severe caries.18,19 Recent evidence also has
supported the role of yeast (Candida albicans) as a
member of the mixed oral microbiota involved in
caries causation.20 These findings provide support
for the ecological plaque hypothesis, which proposes that S. mutans is only one of many endogenous microorganisms involved in the pathogenesis
of caries.11,21,22 A challenge for researchers is to

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September 2009

characterize this complex biofilm and subsequently

identify microbial risk factors leading to caries
activity, with a view toward developing novel
antimicrobial interventions.
Dietary factors. Dental caries cannot occur in
the absence of dietary fermentable carbohydrates
and, therefore, it has been characterized as a
dietobacterial disease.23 Since the original observations of Miller,2 researchers have recognized fermentable carbohydrates as the fuel for the caries
process, and in the 1940s, Stephan24,25 demonstrated the relationship between caries and sugar
exposure, leading to the acidification of dental
plaque. Moreover, Weiss and Trithart26 reported a
direct relationship between caries experience and
the frequency of between-meals consumption of
sweet snacks, which findings supported those of
the earlier Vipeholm study in Sweden.27
The role of specific sugars was a subject of great
research interest in the latter half of the 20th century.28 Sucrose (table sugar) has a unique role as
the sole substrate for glucosyltransferases (bacterial enzymes) involved in the synthesis of extracellular glucan, which is an important microbial virulence factor (discussed above). The relative
cariogenicity of starches as compared with that of
sugars has been the subject of considerable controversy.29 Available studies with humans have not
supported the cariogenicity of starches.29 For
example, Newbrun and colleagues30 reported that
people with hereditary fructose intolerance who are
unable to eat fructose and sucrose but consume
large quantities of starch have a much lower caries
experience than do those without fructose intolerance. Highly processed starch-containing foods,
however, have the potential to be cariogenic, especially when combined with sugars, because they
are able to prolong food retention on tooth
The recognition of sucrose as a major factor in
dental caries, as well as work by Bibby33 regarding
ABBREVIATION KEY. ACP: Amorphous calcium phosphate. bis-GMA: Bisphenol-A glycidyl methacrylate.
CAD-CAM: Computer-aided design/computer-aided manufacturing. CO2: Carbon dioxide. Er,Cr:YSGG: Erbiumchromiumdoped yttrium scandium aluminum garnet.
Er:YAG: Erbium-doped yttrium aluminum garnet. FOTI:
Fiber-optic transillumination. ICDAS: International
Caries Detection and Assessment Criteria. LED: Lightemitting diode. MS: Mutans streptococci. Nd:YAG:
Neodymium-doped yttrium aluminum garnet. OCT:
Optical coherence tomography. QLF: Quantitative lightinduced fluorescence.

the cariogenicity of snack foods, precipitated a

series of ADA conferences in the late 1970s and
early 1980s that culminated in a consensus conference in 1985.34 The conference participants considered several approaches for testing foods to determine their potential cariogenicity, including models
involving animal caries, human plaque acidity and
demineralization and remineralization. They recommended an integrated approach that involved
using combinations of methods to determine the
cariogenicity of foods. They reached a consensus
that foods had no cariogenic potential if their
human plaque pH profiles were statistically equivalent to that of sorbitol. Unfortunately, characterization of foods as having low cariogenic potential
has not proven to be practical because of individual
variability in eating frequency, sequence of eating
foods, timing of eating (such as eating before bedtime) and after-eating behaviors (oral hygiene, fluoride use, gum chewing).28 It also has been challenging to apply information about food cariogenicity in dietary counseling.35 In the latter part of
the 20th century, scientific interest in the cariogenicity of foods waned with recognition that the
prevalence and severity of caries were declining,
and the U.S. government placed less emphasis on
the need for labeling food regarding its
Host salivary and genetic factors. Hostrelated factors are important contributors to a
persons dental caries susceptibility, resistance or
both. It is well established that saliva plays an
important role in the health of soft and hard tissues in the oral cavity.36 Chronically low salivary
flow rate is one of the strongest indicators of
increased caries risk.37 A subjective complaint of
xerostomia often does not correlate with objective
findings of reduced salivary flow rate.38 This
finding has led to clinical recommendations and
guidelines for the clinical assessment of hyposalivation.39 The objective measurement of salivary
flow is an important cornerstone of caries risk
assessment and management.
Researchers initially believed that genetic factorssuch as tooth morphology, position and occlusion; tooth eruption time and sequence; salivary
composition; and sweetness preferencewere less
important in determining caries risk than were
environmental influences, such as microbial and
dietary factors.40,41 However, results of recent
studies in populations of twins have shown that
genetic factors may explain more than 50 percent
of the variance in caries experience among

people.42,43 Much remains unknown about geneticenvironmental relationships in caries etiology and
risk assessment, but the future holds interesting
possibilities for improvements in caries diagnosis
and prognosis.

Risk assessment. Caries risk assessment is the

cornerstone of patient-centered caries management. It is the determination of the probability of a
persons developing new carious lesions during a
specific period41 and of the probability of a change
in the size or activity of existing lesions across
time.44 It is useful in determining whether additional diagnostic procedures are required; in identifying patients who require caries-control measures;
in assessing the effectiveness of attempts to control
caries; and as a guide in treatment planning and
scheduling recall appointments.44 Investigators
have shown that previous caries experience is the
best predictor of future caries experience in primary teeth, followed by parental education and
socioeconomic status; young childrens age at the
time of MS colonization also was found to be an
important risk factor.45 While previous caries experience may be the most useful criterion for risk
assessment, the information arises too late to be
useful in preventing caries because many irreversible events already have taken place. To enable
effective prevention, researchers must determine
efficient ways to identify children at high risk of
developing caries earlier, shortly after their first
teeth erupt. To accomplish this goal, researchers
must develop molecular and genetic methods to
improve the identification and characterization of
cariogenic microbes and identify ways to reduce or
eliminate harmful effects of their colonization. It
also will be important to develop improved technology to detect and quantify early lesions and to
assess carious lesion activity directly, because this
may prove to be the best strategy to identify
patients in need of intensive caries prevention
Fluoride. American contributions to fluorides
role in caries prevention are seminal. They began
at the turn of the 20th century when Frederick
McKay,46 a practicing dentist, associated mottled
enamel47 with reduced susceptibility to caries; in
collaboration with H.V. Churchill,48 the chief
chemist at the Aluminum Company of America, he
later traced this condition to fluoride. H. Trendley
Dean, the first director of what then was called the
National Institute of Dental Research (now the
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September 2009


National Institute of Dental and Craniofacial

Research), conducted several studies in the 1930s
and 1940s with colleagues that provided the conclusive epidemiologic evidence linking what they
referred to as dental fluorosis or enamel fluorosis to excessive fluoride in drinking water.49-51 In
these studies, Dean and colleagues52 also found
that dental fluorosis was associated with lower
caries experience, and their findings served as the
basis for determining the optimal level of water fluoridation for preventing caries and minimizing
dental fluorosis. This research led to the establishment of the first community water fluoridation program targeted at caries prevention, a program that
began in January 1945 in Grand Rapids, Mich. The
results of clinical trials of dietary fluoride supplements resulted in recommendations by the ADA for
fluoride supplementation for people who did not
have access to fluoridated water.53 During the
1940s and 1950s, American researchers, building
on the work of scientists throughout the world,
investigated the synthesis of fluoride compounds
and their potential use in toothpaste for preventing
caries. Scientists from Indiana University, Indianapolis; The Forsyth Institute, Boston; and the
University of Rochester, Rochester, N.Y., conducted
research regarding the inclusion of fluoride in dentifrices.54,55 Interestingly, one of the earliest studies
by Bibby56 involving a dentifrice formulated with
sodium fluoride did not prove successful, because
the presence of calcium in the abrasive interfered
with the action of the fluoride ion.57 The results of
subsequent clinical trials with improved formulations provided conclusive evidence of fluorides
caries-preventive benefits when applied topically,
particularly in children.58-61
American scientists contributed to the paradigm
shift in which fluorides predominant effect became
viewed as mostly posteruptive and topical. Epidemiologic evidence demonstrated that water fluoridation decreased caries prevalence in both children and adults. The results of animal experiments
and clinical trials supported topical fluoride application and the safe and effective use of fluoride.62
American cariologists contributed to knowledge of
the physicochemical aspects of fluoride-enamel
interactions, the influence of fluoride on the demineralization and remineralization process,63-65 and
the pharmacokinetics of fluoride in the oral
Diet. Use of fluoride has reduced the need for
strict dietary control of sugar.69 The effectiveness of
dietary measures to control caries is limited

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September 2009

because modern diets are complex and contain

many natural sugars, refined sugars and sugar
substitutes. However, reducing the amount and
frequency of sugar consumption, including the
hidden sugars in many processed foods, is important for people at high risk of experiencing caries.
Parents and caregivers of young children can
reduce childrens caries risk by limiting their consumption of sugar-containing soft drinks70,71 and
increasing their consumption of milk and other
dairy products.72,73 Dairy products have properties
that protect teeth against caries,74 and eating
cheese after exposure to sugar rapidly neutralizes
plaque acidity.75
A wide range of sugar substitutes have low or no
cariogenic potential.76 For example, sucralose is a
high-intensity noncariogenic sweetener,77 and xylitol has been reported to have anticariogenic properties.78 Chewing sugar-containing gum increases
caries risk,79 but chewing sugarfree gum after
meals can reduce caries risk.80 Some food additives
may have protective properties that reduce cariogenicity; for instance, cranberries can reduce bacterial adherence and glucosyltransferase activity of
S. mutans,81 and tea extracts inhibit salivary amylase activity.82
Sealants. Dental scientists in the United States
have been key players in developing ways to
manage and control caries. In 1955, Michael
Buonocore,83 a researcher at the Eastman Dental
Center in Rochester, N.Y., described etching
enamel to improve retention of restorative
materials. Seven years later, R.L. Bowen,84 a scientist at the ADA Research Unit at the National
Bureau of Standards (now the ADA Foundations
Paffenbarger Research Center), obtained a patent
for restorations with a tooth-colored plastic,
bisphenol-A glycidyl methacrylate (bis-GMA).
These two developments initiated a rich era of
adhesive dentistry involving sealants and restorative materials that improved caries prevention and
tooth conservation.85 Sealants prevent food from
collecting in molar pits and fissures and, therefore,
prevent dental caries.86-89 The placement of sealants
over carious lesions arrests the disease process88-92
and is cost-effective compared with routine restorative care.93,94
Remineralization. Joseph Head, a physician
and dentist who practiced dentistry at the Jefferson Hospital in Philadelphia, observed that
demineralized enamel could be rehardened to the
point at which the enamel could no longer be
scratched by a lancet.95 Decades later, researchers

conducting clinical studies in Europe demonstrated

that incipient caries could be repaired by saliva
when fluoride application was combined with regular removal of overlying plaque.96-98 These observations were corroborated by Koulourides and colleagues at the University of Alabama,99-101 who
demonstrated in situ that saliva rehardens incipient enamel lesions and small amounts of fluoride
accelerate the process greatly, resulting in a highly
caries-resistant enamel surface. Numerous other
researchers throughout the world also have contributed to our current understanding of remineralization. Partially demineralized enamel and
dentin apatite crystals can be remineralized to
almost their original size under optimal laboratory
conditions. However, once the mineral phase is lost
completely, remineralization is not possible.102,103
The process is diffusion-controlled, and most
remineralization occurs at the surface. This leaves
a sealed surface102 that is more resistant to subsequent demineralization than is sound enamel.101
Nevertheless, attempts to remineralize subsurface
areas of the lesion have continued.104,105
The reversal of incipient carious lesions led to a
paradigm change for caries management, generating great interest in developing new and better
remineralizing therapies. Much of this research is
focused on calcium-containing preparations such as
amorphous calcium phosphate (ACP), which was
developed for dental use by Ming Tung, a
researcher at the ADA Foundations Paffenbarger
Research Center,106 and data suggest that some of
these preperations have remineralizing properties.107 Commercial products that contain ACP
and preparations of casein derivatives (casein
phosphopeptide-ACP complex) are commercially
available. Studies have yet to show conclusive evidence of effectiveness in clinical trials108; none has
been shown to be more effective than fluoride.

Clinical methods. Visual detection of caries was

described as early as 1801, in a book entitled
Skinner: A Treatise of Human Teeth.109 One of
the most important early contributions to diagnosis
of dental caries came from G.V. Black, who was a
practicing dentist before becoming dean of the
Northwestern University School of Dentistry in
Chicago.110 Black110 was among the first to
describe, in explicit detail, methods of visual and
tactile detection of dental caries as part of an oral
examination, including the cleaning and drying of
teeth and the use of explorers, that still are in use

100 years later. For detection of proximal caries,

Black described the use of separators to directly
visualize areas of concern and the use of ligatures
(dental floss) passed through the contact point to
detect surface roughness and breakdown.110
Blacks diagnostic methods laid the groundwork
for future criteria for the detection of dental
caries.111-113 Radike111 described detailed criteria for
the visual and tactile detection of dental caries that
until recently were used widely in epidemiologic
and clinical research. They relied heavily on an
explorer catch for detection of caries on occlusal
surfaces and recorded cavitated lesions, but not
noncavitated lesions. Because it favored reliability
and comparability, it was the predominant diagnostic system used in the United States.114 Since
the days of Black, our diagnostic understandings
have been far more advanced than simply diagnosing caries at the level of cavitation.115 The latest
contribution to visual diagnostic criteria for caries
are the International Caries Detection and Assessment Criteria (ICDAS), the development of which
involved a joint effort of international cariologists
with significant contributions from the United
States, particularly from the University of
Michigan, Ann Arbor, and Indiana University,
Indianapolis.116 ICDAS was designed to facilitate
the standardized diagnosis of caries on all tooth
surfaces at all stages of severity. An updated version of ICDAS (ICDAS II)117 has been well accepted
in the United States and has been used in clinical
studies with good intraexaminer and interexaminer agreement, as well as satisfactory sensitivity
and specificity.71,116,118-120
Radiographic methods. Less than six months
after W.C. Roentgens discovery of the x-ray,
William J. Morton,121 a New York physician, was
one of the first to report (during a meeting of the
New York Odontological Society) that x-rays could
have dental applications. Soon afterward,
C. Edmund Kells,122 a dentist practicing in New
Orleans, reported on the role of radiographs in dentistry. Howard R. Raper, a member of the faculty at
the Indiana University School of Dentistry, further
advanced dental radiography by writing the first
book on the topic,123 and in 1925, he perfected the
intraoral bitewing radiograph, which to this day
remains the conventional method for detecting
proximal caries.124 More recent developments
include higher-speed film and digital radiography.
Current digital imaging technologies generate
images whose diagnostic yield may equal, but not
necessarily exceed, that of images obtained by
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September 2009



Key events in the United States involving restorative materials and

technologies for managing single-tooth problems caused by caries.*


Early Restorative Materials


Introduction of various restorative materials: gutta-percha, cohesive gold foil, zinc phosphate restorative material and
cement, silicate cement


First experiments with copper-containing amalgam and formulation of low-copper amalgam alloys


Development of high-copper and zinc-free, high-copper dental amalgam; fluoride-releasing dental amalgam; mercury-free
silver filling material

Dental Amalgam

Resin-Based Sealing and Restorative Materials


Introduction of polymethyl-methacrylatebased direct restorative materials


Patenting of bisphenol-A glycidyl methacrylate (bis-GMA)based dental composites


Introduction of commercial dental composites, commercialization of bis-GMAbased sealants; patenting of radiopacifiers

for composites


Development and commercialization of flowable, packable nano and trimodal composites for dental use


Development and commercialization of acid-etching, enamel and dentin bonding systems


Introduction of glass ionomer restorative materials and glass ionomer admixture with amalgam alloy


Introduction of glass ionomer materials for use with atraumatic restorative technique


Introduction of resin-modified glass ionomers


Introduction of use of zinc oxide eugenol as a cement


Development of first strict formulation of zinc phosphate cement, commercial cavity varnish and calcium hydroxide pulpcapping material


Development of first hard-set calcium hydroxide composition


Introduction of porcelain jacket crown, lost-wax casting process


Placement of the first Vitallium (Austenal Laboratories, now Dentsply Austenal, York, Pa.) screw implant


Development of titanium casting for single-unit and multiple-unit restorations; patenting of commercial porcelainbonded-to-metal system


Introduction of the first blade-vent implants

~1974- ~1985

Development of plastic extracoronal laminate veneers and subsequent intracoronal porcelain veneers

Adhesive Systems

Glass Ionomers

Varnishes, Liners and Bases

Indirect Restorative Materials for Single Units

using conventional film.125

Other technology-based detection methods.
Technology-based dental caries detection methods
first arose in the United States more than 40 years
ago. In 1968, Lees and Barber126 first suggested the
application of ultrasound in dentistry, and in 1970,
they and Lobene127 published early research
regarding its use for caries detection. The early
applications of electrical conductance128,129 and
fiber-optic transillumination (FOTI)130 in caries
detection had their roots in the United States. A
digital version of the latter system (digital imaging
[DIFOTI], Electro-Optical Sciences, Irvington,
N.Y.),131 was tested in the laboratory132,133 and later

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September 2009

evaluated in clinical studies.134,135 Optical coherence

tomography (OCT)which is similar in operation
to ultrasound imaging, but uses light waves rather
than sound waveshas been used in dentistry for
nearly a decade.136,137 Polarization-sensitive OCT is
a variation of conventional OCT that uses polarized
incident light to create images and quantify
caries.138 Fluorescence has received considerable
attention because teeth fluoresce under the excitation of ultraviolet rays.139,140 This idea later led to
the development of the quantitative light-induced
fluorescence (QLF, Inspektor Research Systems
BV, Amsterdam) method in Europe, which has
been studied extensively by investigators at


Cavity Preparation and Restoration Equipment


Development of rubber dam, foot-treadle dental engine (700 revolutions per minute [rpm]), electric dental engine (1,000
rpm), steel dental burs


Introduction of automated amalgamation equipment


Introduction of diamond cutting instruments, high-speed dental engine (>10,000 rpm) and tungsten carbide burs


Development of ball-bearing high-speed handpiece (25,000 rpm)


Development of water-turbine (50,000 rpm), belt-driven (150,000 rpm) and air-turbine (300,000 rpm) high-speed


Commercial development of ultraviolet-light and visible-lightcuring units


Development of carbon dioxide (CO2), neodymium-doped yttrium aluminum garnet (Nd:YAG), erbium-doped yttrium
aluminum garnet (Er:YAG) and erbium-chromiumdoped yttrium scandium aluminum garnet (Er,Cr:YSGG) hydrokinetic
lasers for dentistry


Introduction of air-abrasion cutting equipment for dental use


Development and introduction of high-torque electric dental handpiece


Introduction of second generation of computer-aided design/computer-aided manufacturing (CAD/CAM) equipment


Introduction of commercial light-emitting diode (LED) light-curing units

* Sources: Buonocore,83 American Dental Association,149 Bayne and Thompson,150 Bower and Marjenhoff,151 Gelbier,152 Mahler,153 Rueggeberg,154
Schulein,155 Thompson and colleagues156 and Wilwerding.157

Indiana University.141-144 QLF is a promising and

nondestructive method of detecting and quantifying carious lesions. It allows for longitudinal clinical monitoring of carious lesions and potentially
can determine carious lesion activity.145 In the late
1990s, European researchers introduced an
infrared laser fluorescence device (DIAGNOdent,
KaVo Dental, Biberach, Germany) for caries detection. It is based primarily on fluorescence absorption by bacterial by-products in porous carious
lesions. Researchers have evaluated this device in
research settings146,147 and as an oral health
screening tool in public schools.148

Restorative materials. The effects of prevention

on caries prevalence and the advantages of
improved dental materials have shifted the focus in
caries management from surgical methods and
restoring tooth structure to development and use of
dental materials to prevent disease, remineralization procedures, minimally invasive treatments for
difficult-to-access regions and materials with which
early lesions can be impregnated to prevent further
The table summarizes key historical events in
the United States involving restorative dental
materials, equipment and techniques related to the
treatment of dental caries in single teeth.83,149-157
Whereas this table focuses on accomplishments in

this country, we should note that scientists in

Japan (who developed dentin bonding systems and
glass ionomers, for example) and Europe (who
developed dental amalgam, silicate cements, microfill composites, hybrid composites and glass
ionomers, among others) also have made many significant contributions.
Continuing dental caries disease usually results
in tooth loss. Contributions related to restoration
for tooth replacement are not included here.
Throughout the long history of restorative dentistry, U.S. dental companies have developed many
specialized hand instruments, dental burs, diamond cutting instruments and special finishing
instruments. All of these technical developments in
materials and treatment to restore carious lesions
have involved a strong partnership of academic,
corporate, association-based and governmental
dental research entities and scientists. We
acknowledge the progress they have enabled dentistry to achieve in fighting oral disease.

Dental caries is a dynamic dietomicrobial disease

involving cycles of demineralization and remineralization. The early stages of this process are
reversible by modifying or eliminating etiologic factors (such as plaque biofilm and diet) and increasing protective factors (such as fluoride exposure and salivary flow). This approach manages
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September 2009


dental caries by means of prevention and cure,

reserving surgical approaches for those whose disease severity and tissue loss leave no other option.
Our understanding of caries has changed
markedly in the last century. A National Institutes
of Health consensus statement112 acknowledged
that tooth restoration does not stop the caries
process and emphasized the need for improved
diagnosis, prevention and management of caries in
its early (that is, noncavitated) stages. Still, dental
practitioners and researchers alike have an incomplete understanding of the natural history of
caries. Cognizant of the limitations of current clinical diagnostic methods and concerns about potential disease progression, dentists tend to err on the
side of more aggressive operative treatment than
often might be warranted.
Dentistry needs new diagnostic tools and treatment methods to support improved patient care.
Future caries management must include risk
assessment to enable clinicians to provide timely
and cost-effective care to those most in need. We
have made much progress in our knowledge of the
biology, prevention, diagnosis and treatment of
dental caries since the founding of the ADA 150
years ago. However, dental caries remains a significant problem for many Americans, and we look
forward to the day when people of all ages and
backgrounds view dental caries as a disease of
the past.
Disclosure. None of the authors reported any disclosures.
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The biology, prevention, diagnosis

and treatment of periodontal diseases
Scientific advances in the United States
Gary C. Armitage, DDS, MS; Paul B. Robertson, DDS, MS

he contributions of
researchers in the United
States to scientific
advances in the biological
understanding, prevention,
diagnosis and treatment of periodontal diseases during the past 150
years have been characterized by scientific partnerships among a dedicated practicing profession, substantial public and private-sector research
activity, extensive international collaboration, and strong support from
the National Institutes of Health,
Bethesda, Md. This overview focuses
on the discovery of relationships
between dental plaque and the host
periodontal tissues, and it highlights
only a fraction of the pioneers who
shaped new approaches to periodontal
disease prevention and treatment.
Taken collectively, these efforts have
fundamentally changed our understanding of periodontal infections and
constitute a revolution in how clinicians treat patients with periodontal



Throughout the 19th century and first

half of the 20th century, many theories existed regarding the underlying
causes of gingivitis and periodontitis.
Among the proposed causes were
physiological degeneration of periodontal tissues secondary to aging, circulatory problems, gout, nutritional
deficiencies, endocrine disturbances,
occlusal trauma, dystrophic anomalies
in tooth development, and mechanical
irritation arising from local factors

JADA, Vol. 140

Background. Major scientific advances in periodontology in the
past 150 years have fundamentally changed how clinicians detect and
treat periodontal diseases. These advances include the demonstration
that gingivitis and periodontitis are biofilm-induced infections caused
by components of the indigenous oral microbiota, and that host
inflammatory-immunologic responses to these microbial challenges
are responsible for most of the observed tissue damage.
Types of Studies Reviewed. In this brief overview, the authors
focus on the discovery of the relationships between dental plaque and
the host periodontal tissues. They highlight some of the pioneers in the
United States who shaped new approaches to prevention and treatment
of periodontal disease.
Results. Biofilms that cause gingivitis and periodontitis are complex
polymicrobial communities that are resistant to antimicrobial agents
and host defense mechanisms. An increased understanding of natural
inflammation-resolving mechanisms suggests that control of inflammation is at least as important as is antimicrobial therapy in the treatment of periodontal infections. Data from randomized controlled clinical
trials have shown that most conventional forms of periodontal therapy
are effective as long as patients comply with posttreatment maintenance programs.
Conclusions. Many mechanisms involved in the repair and regeneration of periodontal tissues have been identified. Results of laboratory
studies of factors that enhance prevention and treatment of periodontal
disease have made the transition to clinical practice. Advances in the
fields of molecular biology, human genetics and stem cell biology have
set the stage for significant discoveries that will pave the way for the
development of procedures needed for the predictable regeneration of
periodontal tissues. As a result, new generations of people in the United
States can expect to retain a healthy and functional dentition for
a lifetime.
Key Words. Scientific advances; periodontology; dental history.
JADA 2009;140(9 suppl):36S-43S.
Dr. Armitage is the R. Earl Robinson Distinguished Professor, Division of Periodontology, Department
of Orofacial Sciences, School of Dentistry, University of California, San Francisco, 521 Parnassus
Ave., C-628, Box 0650, San Francisco, Calif. 94143-0650, e-mail
Address reprint requests to Dr. Armitage.
Dr. Robertson is a professor and dean emeritus, School of Dentistry, University of Washington,

September 2009

such as calcified deposits.1,2 Most of these theories

were supported by little or no scientific evidence.
After experimental proof of the germ theory of disease was provided in 1876, some investigators,
including Willoughby D. Miller, believed that bacteria played an important etiologic role in periodontal diseases.3 However, the concept that bacteria were the principal cause of gingivitis and
periodontitis in susceptible people did not become
mainstream thought until 75 years later.
Advances in microbiology of periodontal
diseases. The classical experimental gingivitis
studies conducted by Harald Le and colleagues in
the mid-1960s resulted in a major shift in how scientists and clinicians viewed the etiology of periodontal diseases.4,5 These studies showed that gingivitis developed in all volunteers who refrained
from oral hygiene procedures for a three-week
period and that reinstitution of daily dental plaque
removal resulted in a return to gingival health.
During the development of gingivitis and subsequent return to health, qualitative changes
occurred in the composition of the dental plaque
In addition, in 1967 Stanley R. Saxe and colleagues6 at the University of Kentucky, Lexington,
reported a strong association between dental
plaque accumulation and the development of periodontal disease in beagle dogs. These investigators
demonstrated that tooth cleaning every other day
for 18 months was associated with clinically
healthy periodontal tissues; however, quadrants of
teeth in the same dogs that were not cleaned developed gingival inflammation and attachment loss.6
In Sweden, Jan Lindhe and colleagues7 confirmed
these findings by showing that experimental gingivitis in most beagle dogs progressed to periodontitis across a four-year period if dental plaque was
not removed on a daily basis; control animals that
underwent daily plaque removal via investigatorapplied oral hygiene procedures during the same
period did not develop gingivitis or periodontitis.7
Among many critically important studies of the
microbiology of periodontal diseases, several are
historically significant. In 1964, Paul H. Keyes and
Harold V. Jordan8 of the National Institute of
Dental Research showed that periodontitis could be
transmitted from periodontitis-affected Syrian
hamsters to healthy animals by inoculating the
healthy animals with Actinomyces viscosus from
the diseased animals. One decade later, Michael G.
Newman and colleagues9 reported that patients
with periodontosis (that is, localized aggressive

periodontitis) harbored a disease-specific subgingival microbiota; this finding challenged the prevailing assumption that periodontosis was a degenerative disease and suggested strongly that the
disease was an infection.
According to Fine,10 the results of studies conducted by Theodor Rosebury and his students
Solon A. Ellison and John B. MacDonald of the
pathogenic potential and virulence of the aerobic
and anaerobic components of the indigenous oral
microbiota supported the concept that gingivitis
and periodontitis are infections. The advent of
improved laboratory methods for culturing anaerobic bacteria revealed that some bacteria in plaque
are more important than others as causative
agents of periodontal infections. Moreover, these
studies concluded that periodontal infections are
not caused simply by an increased quantity of
dental plaque on the teeth; rather, the composition
of the microbial community is of considerable etiologic importance.10 A historical review11 of evidence
supporting the bacterial etiology of periodontal diseases includes many scientists who contributed to
these major advances in periodontal microbiology,
notably Ronald J. Gibbons, Sigmund S. Socransky, Anne D. Haffajee and Anne C.R. Tanner
at the Forsyth Institute, Boston, and Lillian V.
(Holdeman) Moore and William E.C. Moore12 at the
Virginia Polytechnic Institute, Blacksburg, Va.
Walter J. Loesche13 summarized this concept in
a discussion of nonspecific versus specific
hypotheses regarding the microbial etiology of
periodontal infections. Some authorities, including
Rosebury, favored the nonspecific plaque hypothesis in which increased numbers of indigenous bacteria (that is, an increased plaque biomass) overwhelm host defenses and result in periodontal
disease. Other investigators, such as MacDonald,
favored the specific plaque hypothesis in which a
small number of specific bacteria are responsible
for triggering the tissue damage observed in
inflammatory periodontal diseases.10
In the 1990s, Socransky and colleagues14 used
cultivation methods and DNA probe technology to
show statistically significant associations between
clusters of indigenous bacteria in the subgingival
microbiota and the presence and progression of

ABBREVIATION KEY. GTR: Guided tissue regeneration.

OPG: Osteoprotegerin. RANK: Receptor activator of
nuclear factor kappa B. RANKL: RANK ligand.
RCTs: Randomized clinical trials.
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highly likely that the other, yet-to-becultivated 50 percent contains microorganisms that are of etiologic importance or play important roles in
biofilm ecology. Many investigators
are applying gene-detection methods
to determine the presence of uncultivable components of dental
biofilms.19-22 What has emerged from
this work is the extraordinary diversity of oral microbiota in health and
disease. It is likely that this work will
lead to a better understanding of how
oral biofilms form, mature and
interact with the host to cause disease. Novel treatment approaches and
intervention strategies will result
Researchers at a National Institute of Dental Research conference on dental plaque
discoveries dealing with the
(Airlie Center, Warrenton, Va.; circa 1975). Kneeling (left to right): Ernest Newbrun,
of biofilm-host
Walter Loesche, Harald Le, Robert Genco, Thomas Valega. Standing (left to right): Paul
Keyes, unknown, Ronald Gibbons, Sigmund Socransky, Roy Page, William Bowen,
Anthony Rizzo, Thomas Temple, Jan Carlsson, James English, John Goggins, Bernard
Advances in pathogenesis of
Guggenheim, Max Listgarten, William McHugh, Robert Fitzgerald. Photograph courtesy
of Richard Ellen. Reproduced with permission of Marcia Gibbons.
periodontal diseases. The early history of periodontal pathogenesis was
periodontitis. It became clear that bacteria such as
dominated by the premise that all people are
equally susceptible to developing periodontitis and
Porphyromonas gingivalis, Tannerella forsythia,
that untreated gingivitis progresses to periodonTreponema denticola, Campylobacter rectus,
titis linearly over time. On the basis of general
Micromonas micros, Streptococcus intermedius,
medical pathology models, researchers believed
Eubacterium nodatum, Aggregatibacter (formerly
that most of the destruction of periodontal tissues
Actinobacillus) actinomycetemcomitans and Preduring the course of the disease was due to inflamvotella intermedia are important members of the
matory or degenerative/atrophic processes.23 Until
consortium of microorganisms that cause
the late 1960s, researchers based their studies priThe major microbiological conclusions estabmarily on observations and individual interpretalished during this period include the following:
tions of the histologic changes in the diseased tisdperiodontal infections are polymicrobial;
sues. A consistent observation was that the
dthe causative agents are part of the indigenous
affected tissues were chronically inflamed at both
(normal) microbiota;
the clinical and histologic levels. Unfortunately,
dthe amount of dental plaque is of etiologic
the results of morphological studies alone were
unable to explain the mechanisms responsible for
dsome bacteria in dental plaque are more pathothe tissue destruction at inflamed sites.
genic than others.
When the results of microbiological studies
Of equal scientific importance was the demonshowed clearly that gingivitis and periodontitis are
stration by several groups, including those led by
infections, investigators began to unravel the comJohn W. Costerton and colleagues15 and Paul E.
plex mechanisms of how bacteria could trigger
Kolenbrander and colleagues,16 that dental plaques
destructive inflammatory responses by the host. In
are highly organized bacterial biofilms. From a
addition, innovative ultrastructural studies contherapeutic perspective, these biofilms are complex
ducted by Max A. Listgarten24 clarified the relapolymicrobial communities that are resistant to
tionship of junctional epithelium to the tooth. He
externally applied antimicrobial agents and
also made major contributions to understanding
antibacterial host mechanisms.17
interactions between microbiota and periodontal
It is now known that only about 50 percent of
tissues in health and disease.25
the oral microbiota can be grown in the laboratory
In 1976, Roy C. Page and Hubert E. Schroeder26
by using modern cultivation techniques. It is
documented a dynamic series of inflammatory

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September 2009

events in the development of periodontal lesions.

After decades of work by many researchers, it
became clear that the progression of periodontitis
was neither linear nor an automatic consequence of
gingivitis; rather, it could assume a number of clinical presentations depending on the nature and
radius of effect of the infecting bacteria, periodontal anatomy, genetic predisposition and expression of the host inflammatory response. Critical
variables also included the size, location and composition of the biofilm; the frequency and duration
of epithelial ulceration; the everyday habits of the
host; and the regularity of oral care.
Indeed, most of the tissue damage found in
patients with periodontitis appeared to result from
host responses to bacterial challenges rather than
from direct lytic effects of the pathogenic microbiota. Moreover, results of practice-based studies
challenged the prevailing concept that all patients
are equally susceptible to periodontal infections,
because some did not respond well to conventional
treatment.27,28 The results of longitudinal epidemiologic studies confirmed these observations, demonstrating that only a subset of the population developed severe periodontitis.29,30
In the late 1990s, emerging evidence suggested
that the intensity of inflammation and susceptibility to periodontal damage after a microbial challenge were mediated by the host response, including genetic polymorphisms.31 Observational studies
of twins have shown that a significant portion of
the population variance in periodontal disease
prevalence can be attributed to genetic factors.32,33
Also, it appears likely that genetic changes caused
by environmental insults affect the clinical phenotype observed in patients with periodontal
A number of risk factors associated with periodontitis, such as persistent exposure to microbial
challenges, chronic inflammation, smoking and diabetes, are known to produce strong epigenetic
changes in affected tissues.34 The results of epidemiologic studies indicate that smoking is an
especially important risk factor.35,36 Furthermore,
osteoclast-mediated bone loss, a hallmark of periodontitis, appears to be triggered by a cascade of
host-response events involving the receptor activator of nuclear factor kappa B [RANK]), the
RANK ligand (RANKL) and osteoprotegerin (OPG).
Chronic periodontal inflammation may induce
increases in the RANKL-OPG ratio, which stimulates osteoclast maturation from precursor cells.37
An increased understanding of the inflammatory

response and the natural mechanisms of its resolution suggests that control of inflammation is at
least as important as is antimicrobial therapy in
the treatment of periodontal infections.38 Future
models of the pathogenesis of inflammatory periodontal disease will incorporate genomic, proteomic
and metabolomic data into dynamic biological networks that include mechanisms of disease initiation and resolution.39
Potential effect of periodontitis on general
health. During the past two decades, investigators
have reexamined the possibility that untreated
periodontal infections can have an adverse effect on
general health and that other diseases can contribute to periodontal pathogenesis. The results of
these studies40-42 suggest that untreated periodontitis may be a risk factor for myocardial infarction,
nonhemorrhagic strokes and adverse birth outcomes. In addition, evidence indicates that periodontal infections may interfere with the metabolic
control of diabetes mellitus.40 The presence of such
associations may reflect risk factors common to
periodontitis and other chronic inflammatory diseases. Although this is a highly important area of
ongoing investigation, the results of observational
and interventional studies vary and the relationship between periodontal disease and general
health remains unclear.

Dental calculus. Long before investigators recognized that gingivitis and periodontitis are infections caused by indigenous oral microbiota, many
clinicians observed that the frequent removal of
acquired deposits from teeth resulted in a noticeable improvement in overall periodontal health.
This observation led influential clinicians such as
John W. Riggs43 and G.V. Black44 to conclude in the
1880s that dental calculus was a major local irritant that caused periodontal inflammation. However, no universal consensus existed with regard to
this issue.1,2 As a result of the confusion regarding
the etiology of periodontitis, treatment included a
range of therapies including dietary changes, gingival massage, local application of caustic chemicals, occlusal adjustment, ingestion of patent remedies, removal of local irritants and surgical
resection of affected tissues. In some situations,
dentists and patients considered periodontal disease to be untreatable, with tooth extraction being
the ultimate management strategy.
At the beginning of the 20th century, there were
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September 2009


two major approaches to treatment of periodontitis.

hypothesis that healing patterns of the periodontal
One approach, advocated by many influential pracsoft tissues are determined by the hard tissues
titioners in the United States and Europe, involved
with which they are in contact.49
the use of surgical resection of periodontal pockets
Nonsurgical intervention. Advocates of the
followed by curettage of the underlying bone.44,45
nonsurgical approach to treatment of periodontitis
These practitioners thought that the bone was
included Russell W. Bunting,50 Isador Hirschfeld,51
necrotic or affected by a carious process that
Arthur H. Merritt52 and Dickson G. Bell.53 These
caused chronic osteitis.
Advocates of this
clinicians promoted the concept that most patients
approach considered the soft tissues of the pocket
with periodontitis could be treated satisfactorily
wall to be irreversibly damaged by pus at the site,
without surgical intervention. They believed that
as well as by mechanical irritasurgical intervention was a
tion from dental calculus.
treatment of last resort and
Proponents of the second
should be used only in the most
approach held that the disease
advanced cases in which subginwas caused by local irritation
gival access for scaling and root
from dental calculus, and the
planing was impossible without
underlying bone was not
surgical entry.
affected. Practitioners in this
Scientific data supporting
group included Riggs43 and
either approach to periodontal
William J. Younger46; they
therapy did not exist until publiopposed the gingival resection
cation of a series of studies by a
approach in favor of the nonsurteam of investigators from the
School of Dentistry, University
gical removal of acquired
of Michigan, Ann Arbor. These
deposits followed by a rigorous
critical investigations of the effiprogram of oral hygiene.
cacy of periodontal treatment
By the middle of the 20th
are now known as The Michigan
century, the results of many
Longitudinal Studies.54-58 The
multidisciplinary studies confirmed that the alveolar bone of
team was led by Sigurd P. Rampatients with periodontitis was
fjord, a Norwegian dentist who
neither necrotic nor carious.23 In
came to the University of
addition, the concept that perioMichigan in 1946 to study under
dontal diseases are plaqueBunting, who was then dean of
induced infections was bethe School of Dentistry. RamDr. Sigurd P. Ramfjord. Reprinted with permission
coming widely accepted by the
(see photograph59) earned a
from the American Academy of Periodontology
from Ramfjord.
profession. Many clinicians
masters degree in periodontics
still advocated surgical pocket
and a Doctor of Philosophy
reduction to create a gingival architecture that
degree in pathology and then joined the faculty.60
would facilitate oral hygiene and periodontal mainTaken collectively, these clinical investigations protenance procedures.
vided the first data showing that nonsurgical and
Surgical intervention. Advocates of surgical
surgical forms of periodontal therapy were effective
intervention included Henry M. Goldman,47 Irving
in resolving periodontal infection and inflammaGlickman48 and Saul Schluger.49 Goldman claimed
tion, and they resulted in sustained repair of periothat gingivoplasty would create physiologic gindontal tissues when combined with an appropriate
gival contours that were self-cleansing.47
posttreatment maintenance program.
Glickman stated that scaling and root planing was
Investigators throughout the world have replinot required before surgery and described a
cated these results in many studies.61,62 It now
method for eliminating periodontal pockets that
seems clear that the choice of nonsurgical or surconsisted of the initial resection of the diseased
gical treatment depends on anticipated patientperiodontal pocket wall and subsequent removal of
centered outcomes (such as discomfort, root sensicalculus and smoothing of the tooth surface.48
tivity, esthetics), as well as on traditional clinical
Schluger promoted the use of osseous resection
outcomes, such as a reduction in probing depths
during periodontal surgery on the basis of the
and gains in clinical attachment.62 The Michigan

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September 2009

Longitudinal Studies were randomized clinical

trials (RCTs) that were the first of their kind in
periodontology. Two of Ramfjords legacies were the
introduction of RCTs to periodontology and the promotion of an evidence-based approach to clinical
Adjunctive use of antimicrobials. An important advance in the past 100 years has been clarification of the benefits and limitations of antimicrobial agents as an adjunct to mechanical periodontal
therapy. W.D. Miller3 was among the first to suggest that antiseptics applied topically or via
mouthrinsing might be useful in the treatment of
periodontal diseases. The results of well-conducted
clinical trials demonstrated that topically applied
antiseptics, particularly chlorhexidine, were highly
effective in the treatment and prevention of gingivitis.63 However, use of topical antimicrobials in
the treatment of periodontitis, in which infecting
bacteria are sequestered in biofilms within deep
periodontal pockets, has been less effective. The
results of many clinical trials indicated that irrigating or rinsing with antimicrobial agents as
stand-alone treatments for periodontitis was insufficient to eliminate or control periodontal infections
because of the inherent antimicrobial resistance of
biofilms, as well as difficulties in delivering the
drugs to subgingival sites.64
Pitcher and colleagues65 reported that vigorous
swishing with mouthrinses did not impel the antiseptics into subgingival infected sites. They concluded that the role of topically applied antiseptics
is strictly adjunctive to mechanical disruption and
removal of biofilms. Under such conditions, the
limited adjunctive effects of antimicrobial agents in
treating these infections are enhanced somewhat
by placing slow-releasing vehicle preparations
directly into the periodontal pocket.66
Systemically administered antibiotics gain
access to infected periodontal sites via the circulatory system. In a meta-analysis of data from a
large number of clinical trials, Haffajee and colleagues67 found that systemic antibiotic therapy,
combined with mechanical removal of plaque via
scaling and root planing, had beneficial adjunctive
effects, including gains in clinical attachment
levels and reductions in probing depths. The clinicians decision to administer antibiotics is complicated by the possible development of microbial
resistance to the drug, allergic reactions, gastrointestinal disturbances and other side effects.
Future basic research regarding the mechanisms
of the initiation and maturation of dental plaque

likely will lead to novel therapeutic ways to interfere with and disrupt these disease-producing
Repair and regeneration. Throughout the
first half of the 20th century, many authorities,
including Black, believed that once periodontal tissues were detached from the teeth as a result of
periodontitis, there is no chance whatever for a
reattachment.68 Although this view was not held
universally, it was the prevailing opinion until clinicians began publishing practice-based series of
cases in which therapy resulted in the clinical closure of periodontal pockets with radiographic evidence of osseous repair. Among these publications
was a report by John F. Prichard69 in which treatment resulted in dramatic osseous repair, especially of narrow three-walled defects.
As the field of periodontics matured from 1970 to
2000, investigators in many controlled studies evaluated the effects of periodontal flap procedures
alone compared with flap procedures combined
with the insertion of various bone-replacement
graft materials. In a systematic review and metaanalysis of these studies, Reynolds and colleagues70
concluded that bone-replacement grafts resulted in
statistically significantly increased bone and clinical attachment levels and reduced probing depths
compared with flap procedures alone.
Guided tissue regeneration. The next major
advance in periodontal regeneration was the proofof-principle introduction of guided tissue regeneration (GTR) procedures in 1982. Sture Nyman and
colleagues71 placed a barrier membrane between
the periodontal flap and a tooth scheduled for
extraction in a patient with severe periodontitis.
This procedure temporarily excluded the gingival
epithelium and connective tissue from the osseous
defect and allowed pluripotent cells from the periodontal ligament to colonize the wound. The results
of histologic studies showed partial regeneration of
lost periodontal tissues, including the formation of
new cementum, bone and a functional periodontal
ligament.71 Subsequent investigations reviewed in
a meta-analysis72 of the clinical effectiveness of
GTR procedures suggest that these procedures can
promote gains in clinical attachment levels and
reductions in probing depths.
Also during the past two decades, researchers
have shown an increasing interest in studying the
role of growth factors in tissue repair and regeneration.73,74 Growth factors are naturally occurring
mediators produced by a variety of cells that affect
the complex cascade of events during wound
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September 2009


healing. Growth factors act in a coordinated

fashion that regulates the timing of cell division
and recruitment of progenitor cells, cell differentiation and synthesis of the extracellular matrix.
Scientific progress in this area has led to the isolation of natural growth factors and the development of recombinant forms that have been evaluated preliminarily for their effect on periodontal
regeneration in humans.73 Advances in developmental and molecular biology, human genetics,
proteomics, nanotechnology and stem cell biology
have set the stage for discoveries that likely will
soon allow clinicians to manipulate sophisticated
tissue-engineering procedures required for the predictable regeneration of periodontal structures.74

Major influences on periodontology in the United

States in the past 150 years include strong interrelationships among the American Dental Association, schools of dentistry, clinician-scientist
research centers, private sector industry and insurance carriers, and the practicing dental profession.
The American Academy of Periodontology,
Chicago, also has played a major role in supporting
patient care, encouraging research in periodontal
disease biology and treatment, and promoting
international scientific collaboration. The academy
was founded in 1914 by Drs. Gillette Hayden and
Grace Rogers Spalding. Spalding served as the
editor of the Journal of Periodontology, first published in 1930. Subsequent editors were Maynard
K. Hine, Henry M. Goldman, Timothy J. OLeary,
William C. Hurt, Robert J. Genco and Kenneth S.
Kornman, all of whom made major contributions to
dental research and established the journals reputation for scientific excellence (Alice DeForest,
executive director, American Academy of Periodontology, written communication, June 2009).
The American Association for Dental Research
and the International Association for Dental
Research, Alexandria, Va., have been critically
important in the discussion and dissemination of
research findings applicable to treating periodontal
diseases (Christopher H. Fox, executive director,
American and International Associations for
Dental Research, written communication, June
2009). The National Institute of Dental and Craniofacial Research, Bethesda, Md., has been essential in its support of research that has advanced
the understanding of periodontal disease biology
and treatment.

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September 2009


In the future, periodontal therapy in the United

States will build on the remarkable scientific
advances made during the past 150 years. Although the mechanical removal of biofilms and its
products, combined with professional periodontal
maintenance, will remain a cornerstone of care,
new approaches to the prevention, diagnosis and
treatment of periodontitis are well within sight.
On the horizon are major breakthroughs in
understanding essential mechanisms that mediate
and resolve tissue destruction in periodontal
inflammation. Such discoveries will provide new
tools for regeneration of periodontal structures and
clarify associations between periodontitis and other
chronic inflammatory diseases. The results of fundamental microbiological research will lead to
innovative methods of identifying and altering
pathogenic biofilms. The rapid evolution of implant
therapy as an integral part of periodontal treatment will continue, with major advances occurring
in establishing a ligamentous attachment to alveolar bone. As a result of these scientific advances,
new generations in the United States can expect
to retain a healthy and functional dentition for a
Disclosure. Drs. Armitage and Robertson did not report any
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66. Hanes PJ, Purvis JP. Local anti-infective therapy: pharmacological
agentsa systematic review. Ann Periodontol 2003;8(1):79-98.
67. Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective
periodontal therapy: a systematic review. Ann Periodontol 2003;8:
68. Black GV. A Work on Special Dental Pathology. 2nd ed. Chicago:
Medico-Dental Publishing; 1924:166.
69. Prichard J. The infrabony technique as a predictable procedure. J
Periodontol 1957;28(3):202-216.
70. Reynolds MA, Aichelmann-Reidy ME, Branch-Mays GL, Gunsolley
JC. The efficacy of bone replacement grafts in the treatment of periodontal
osseous defects: a systematic review. Ann Periodontol 2003;8(1):
71. Nyman S, Lindhe J, Karring T, Rylander H. New attachment following surgical treatment of human periodontal disease. J Clin Periodontol 1982;9(4):290-296.
72. Murphy KG, Gunsolley JC. Guided tissue regeneration for the treatment of periodontal intrabony and furcation defects: a systematic review.
Ann Periodontol 2003;8(1):266-302.
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in periodontal wound healing: a systematic review. Ann Periodontol 2003;
74. Slavkin HC, Bartold PM. Challenges and potential in tissue engineering. Periodontol 2000 2006;41:9-15.

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September 2009


A view of the future

Dentistry and oral health in America
Isabel Garcia, DDS, MPH; Lawrence A. Tabak, DDS, PhD

merican social writer

and philosopher Eric
Hoffer wrote, In times
of drastic change, the
learners inherit the
future. The learned usually find
themselves beautifully equipped to
live in a world that no longer
More than 60 years ago, the
National Institute of Dental and
Craniofacial Research (NIDCR) was
created to ensure the dental health
of people in the United States. Since
then, the world of research has
undergone such drastic changes
that, scientifically, the 1940s seem
as distant as medieval times. Our
investments in research have
improved the lives of millions of
people and demonstrated that oral
health is integral to overall health.
Revolutionary tools unimaginable
even a decade ago now are enabling
researchers to unravel the mysteries of oral biology, oral health
and disease. Genomic and proteomic
advances combined with the power
of super-fast computers are profoundly changing our understanding of oral, dental and craniofacial diseases and disorders. More
precise and faster diagnostic tests,


JADA, Vol. 140

Background. New tools are enabling researchers to understand the
mysteries of oral biology and disease and to change profoundly the treatment of oral, dental and craniofacial diseases and disorders. The authors
explore advances in modern science and technology and how they will
change oral health care in the future.
Results. Emerging technologies such as salivary diagnostics, highresolution imaging and nanotechnologies, as well as other new tools will
lead to efficient and highly effective personalized dental treatments. A
new generation of cell-based therapies will be available for regenerating
tissues, and anti-inflammatory drugs and pain medications will be tailored to maximize efficacy and safety. Large teams of clinicians and scientists will tackle increasingly complex problems, and advances in computational sciences will make it possible to create virtual teams across the
world. Information technology systems will enable clinicians to examine
and integrate information obtained from all databases in cyberspace.
Clinical Implications. As scientists discover newer and better
methods to preempt and prevent disease, they must translate these
methods into tools for people at greatest risk of developing disease. Conquering the array of complex diseases that affect the oral and craniofacial
complex will require multifaceted strategies and multidisciplinary
Key Words. Dental research; emerging technology.
JADA 2009;140(9 suppl):44S-48S.

Dr. Garcia is the deputy director, National Institute of Dental and Craniofacial Research, National
Institutes of Health, 31 Center Drive, Building 31, Room 2C39, Bethesda, Md. 20892, e-mail Address reprint requests to Dr. Garcia.
Dr. Tabak is the director, National Institute of Dental and Craniofacial Research, National Institutes
of Health, Bethesda, Md.

September 2009

new drugs and biologics, practice-based research

and culturally sensitive interventions are providing
novel avenues to improve oral health. As more
remarkable discoveries and greater achievements
in science and technology emerge, Hoffers words
give us an irresistible mandate to embrace lifelong

Predicting the future is risky business. In 1977,

Ken Olsen, the president and founder of Digital
Equipment Corporation (headquartered from 1957
to 1992 in Maynard, Mass.), maker of large business mainframe computers, is said to have argued
against personal computers, stating there is no
reason for any individual to have a computer in
[his] home.2 Although the statement was not in
reference to the modern personal computer, the
perceived error in judgment reportedly played a
large role in the companys demise.3
French surgeon Dr. Alfred Velpeau offered a
downbeat view of the future. In 1839, he declared,
The abolishment of pain in surgery is a chimera.
It is absurd to go on seeking it today. Knife and
pain are two words in surgery that must forever
be associated in the consciousness of the patient.4
Fortunately, for both patients and surgeons, this
pronouncement was wrong. Another example of the
perils of forecasting the future came from surgeon
Pierre Pachet, who, in 1872, said that Louis Pasteurs theory of germs is ridiculous fiction.5
Finally, in the oral health arena, the forecasting of
a severe shortage of dentists in the United States
in the mid-1960s was never realized as a result of
unforeseen sharp declines in population growth
and the increased federal support for dental
According to American theoretical physicist
Michio Kaku, We are making the historic transition from the age of scientific discovery to the age
of scientific mastery in which we will be able to
manipulate and mould nature almost to our
wishes.7 Regardless of whether we achieve the
kind of scientific and technological utopia described
by Kaku, it is reasonable to predict that within the
next two decades, science will give us the tools to
short-circuit diseases at the molecular level, to
alter the course of disorders by manipulating defective genes, and to treat conditions by using drugs
or other therapies customized with stealth precision for individual patients.

The visual and tactile methods of dental diagnostics will be augmented by powerful technologies
such as smart imaging systems, genome scans to
evaluate patients responses to pharmaceuticals,
molecularly based diagnostics and integrated electronic risk management systems. Dentists of the
future will rely on a range of diagnostic and treatment tools that rapidly and efficiently process a
patients biological information, from their genes to
their proteins to their metabolites.

Looking beyond the horizon, what changes can we

predict? Can we achieve a future in which prevention and delivery of care empower all Americans to
maintain good oral health for a lifetime? Can we
develop smart, early interventions to avert suffering from chronic orofacial pain or craniofacial
disorders? Will we have the tools to allow clinicians
to recognize oral malignancies at their earliest
stage and short-circuit their progress? Will we successfully bioengineer replacement teeth or discover
small molecules to alter the composition of oral
biofilms? Can the salivary glands be a gateway to
the body for the delivery of precise molecular therapies with few side effects?
Dental research is well-positioned to attain all of
these goals. However, our success will depend not
only on the remarkable advances of modern science
and technology, but also on our ability to achieve
closer integration between dental research, dental
practice and education. Conquering the array of
complex diseases that affect the oral and craniofacial complex will require multifaceted strategies
and multidisciplinary cooperation, not professional
Predictive tools. One area of science that holds
exceptional potential to alter the practice of dentistry is salivary diagnostics. This emerging technology will allow dentists to make a quantum leap
forward in their ability to predict, detect and prevent disease. Consider the following scenario:
On entering a dental office, a new patient will
expectorate into a small vial. A staff member will
load the contents onto a disposable diagnostic chip
about the size of a dime. This all-in-one chip first
will isolate the patients DNA and rapidly decode

ABBREVIATION KEY. NIDCR: National Institute of

Dental and Craniofacial Research.

JADA, Vol. 140

September 2009


Envisioned signatures for oral cancer, breast cancer, type 2 diabetes,

periodontal disease and caries. Adapted with permission of Wong
from The Wong Lab.8

the genetic blueprint of life. This information will

be analyzed for drug response genes, and a staff
member will add automated alerts to the patients
electronic record to ensure that the proper medication dosage will be provided if needed in the future.
This lab on a chip then will scan the saliva to
determine the levels of numerous molecules present in the fluid; within minutes, a detailed report
will be produced. Using specialized software and a
computer, the clinician then will compare unusual
changes in various proteins, antibodies or other
analytes. He or she will use these results as the
baseline measures against which findings from
future visits will be compared. These tests will
enable the early detection of various oral diseases,
as well as reveal signs of developing medical conditions, ranging from cancer to diabetes to various
infectious diseases (see illustration8).
Personalized treatment. In the dental operatory, patients likely will never see or hear a handpiece. Dentists will perform routine examinations
that include use of a high-resolution imaging
device to better visualize the subsurface tomography of each tooth. In places where the enamel


JADA, Vol. 140

September 2009

shows early signs of demineralization, the process

will be reversed with advanced nanomaterials that
deliver biologically based therapies to promote
remineralization naturally. In cases of chronic
periodontal disease, dentists will possess additional
predictive tools to characterize the bacteria underlying the infection and the specific nature of the
immune response, and they will be able to personalize treatments that most effectively target and
eliminate both the bacteria and the infection. In
the rare instances in which the disease persists
and destroys tooth-supporting bone, dentists will
know how to regenerate bone and prevent tooth
Targeted approaches. Dentists also will possess high-resolution imaging devices to visualize
any unusual lesions in the oral cavity. Pervasive
computing, in the form of nanochips that can be
implanted in the mouth or introduced into the circulation or soft tissues, will act as stealth sentinels
yielding real-time information about the patients
health status. They will have an array of tools
available to perform rapid molecular pathological
analysis to help identify premalignant lesions and
take the preemptive steps of characterizing the
internal molecular patterns of these cells (much
like whorls in a fingerprint) and matching them
with a drug that kills the tumor cells selectively,
preserving both healthy tissue and function. To
reduce the likelihood of a recurrence, surgeons will
have sophisticated imaging tools and stains at
their disposal that indicate whether other tumor
cells have spread inconspicuously nearby. Following this fluorescent trail, they will surgically
remove all of the potentially affected tissues.
To treat people with oral autoimmune diseases,
either localized or part of a complex syndrome,
health care professionals will possess much more
sensitive and precise blood- or saliva-based diagnostic tests. These tests will measure levels of
disease-linked antibodies or defense cells as they
begin to amass, but before overt symptoms occur.
They will complement gene-scanning tests that
alert a dentist or physician that his or her patient
has an inherited susceptibility to diseases such as
Sjgren syndrome or diabetes.
Novel biologics and drugs. People who have
disfiguring wounds to the head and face or those
who are born with birth defects will benefit from a
new generation of cell-based therapies to regenerate tissues and heal wounds without common

complications such as scarring, contracture or dysfunction. People with inflammatory diseases will
benefit from a new generation of anti-inflammatory
drugs that will enhance resolution of the immune
response via natural signals to heal and cease the
inflammation, rather than via an attempt to interrupt the immune response. In addition, the large
number of people with chronic orofacial pain conditions will be treated with a new generation of nonaddictive pain medications that will be tailored for
them through the use of pharmacogenomic principles to maximize efficacy and safety while avoiding
dangerous side effects.

clinician with the seminal information needed to

deduce a diagnosis and establish a course of action.

Science changes our lives. Today, we are on the

verge of many opportunities to develop tailored,
preemptive oral health care that will improve the
health of and quality of life for millions of people.
We are embracing new tools and technologies and
applying new biologically based approaches to
solving old problems. But we must be mindful that
science has not reached everyone adequately. Stubborn inequalities in oral health continue to exist
among many groups, communities, cities and
towns. With respect to health disparities in the
United States, it has been said, Thus, it is not
Early science largely was a cottage
given in our genome that there must
industry. By the 1950s, investigators
be inequalities in health. It is a social
began forming small teams (for
fact that most risk factors for
The availability of
example, Watson, Crick and
common diseases, and many
massively scalable
uncommon diseases, are more prevaFranklin) to tackle complex problems
lent among the poor than among the
requiring different sets of expertise.
technology systems
The 21st century already has seen
the self-assembly of large teams of
Dentistry can proudly claim a
will enable clinicians
clinicians and scientists to tackle
record of championing health
of the future to
increasingly complex problems, such
and disease prevention
investigate and then
as decoding the human genome.
strategies, but many of our most
integrate information
Extraordinary advances in computaeffective preventive measures and
obtained from all
tional sciences, such as cloud commessages have never reached those
databases in
puting, have made it possible to
who need them most. As we discover
create virtual teams that span the
and adopt newer and better methods
planet.9 The availability of massively
to preempt and prevent disease, we
scalable information technology sysmust improve our ability to translate
tems will enable clinicians of the future to investiand disseminate these methods effectively into
gate and then integrate information obtained from
tools for communities and people at greatest risk of
all databases in cyberspace. Ironically, these new
developing disease, or we will risk replicating the
approaches will make it easier for the solo practishortcomings of the past.
tioner, who may be physically alone but who will be
How do we turn the corner on health inequalilinked electronically with thousands of people comties? Improving our understanding of what causes
prising the scientific community worldwide.
inequalities at individual, community and societal
Consider the situation in which ones patient has
levels is necessary but not sufficient. Teasing out
an unknown disease in the mouth. The clinician
the underlying biological, behavioral and/or culwill analyze the clinical and laboratory findings
tural factors is necessary but not sufficient. Tarand compare them with anonymized electronic
geted programs and interventions addressing
unique populations are necessary but not
records throughout the globe. He or she then will
link the findings with those of extensive genetic
Systematic action is needed to address oral
studies of every type, as well as with the latest
health inequalities in a rational, purposeful and
findings from clinical trials around the world. The
science-driven way that recognizes both societal
clinician will use software to integrate and help
and personal responsibility for health. Science and
interpret the blizzard of data at his or her disposal.
technology can be a vehicle for eliminating dispariIn the end, predictive algorithms will provide the

JADA, Vol. 140

September 2009


ties if used to root out causes of disease, to reprogram the biology of disease and to target the most
vulnerable people for early intervention. However,
investing in healthy communities and developing
social and economic policies that increase opportunities, education and access to quality health care
will go a long way toward breaking the cycle of
health inequalities. Now is the time for policymakers to consider undertaking a vigorous debate
about how scientific advances could improve the
publics health, given the complexities of our health
care delivery system and the economic and cultural
differences that constitute our nation.

The tools of modern science have surprised,

intrigued and dazzled our imagination. They have
improved the oral health of and quality of life for
countless people and communities. Yet, we have
learned that oral diseases have no anatomical or
disciplinary borders. As we look toward the future
of oral health care and research, our best prospects
for making the next leap toward solving complex
oral diseasesfrom caries to clefting or from rare
craniofacial disorders to oral cancerare by supporting the best science, embracing new avenues of
inquiry and welcoming the expertise of people in
other disciplines.
When Congress established NIDCR more than
60 years ago, our nations oral health was so poor
that one could not have anticipated todays remarkable gains. Scientific research will continue to yield


JADA, Vol. 140

September 2009

exciting technologies and effective treatments.

Dental educators and clinicians will need to rise to
the challenge of adapting to novel ways of providing care and applying new approaches to solving
old problems. Doing so will ensure that our profession is poised to inherit the future.
Disclosure. Neither Dr. Garcia nor Dr. Tabak reported any
The authors acknowledge the contributions of Mr. Bob Kuska and
Ms. Alison Davis to the manuscript of this article.
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