Special Report: Nobel Thinking for Dentistry

EDITOR’S NOTE: Bound to have significant ramifications on all facets of health care, this breakthrough research and the emerging field of precision medicine will facilitate individually tailored treatment regimens. Due to the nature of this firsthand report, this article has not undergone peer review.

Spend a week at the Grand Hotel in Stockholm hanging around Nobel Prize winners and their brilliant colleagues and you start to think big. I know, because I had the amazing honor of watching my father, Tomas Lindahl, PhD, accept a Nobel Prize in Chemistry in December.

The 2015 Nobel Prize in Chemistry recognized the emerging field of DNA repair. Along with my father, from the Francis Crick Institute and Clare Hall Laboratory in Hertfordshire, United Kingdom, the award honored Paul Modrich, PhD, of the Howard Hughes Medical Institute and Duke University School of Medicine in Durham, North Carolina, and Aziz Sancar, MD, PhD, of the University of North Carolina, Chapel Hill. Specifically, my father’s experiments revealed that DNA — the building block of life — was not a stable molecule as everyone had assumed. Instead, this vital molecule at the heart of our very existence is constantly breaking — but what makes life possible is there are chemical ways in which it repairs itself.

While this finding may seem far removed from the day-to-day practice of dentistry, in the big picture, this research will lead to fundamental changes in patient treatment across all facets of health care. If we can understand the mechanics of DNA and how it repairs itself, we could develop innovative ways to approach treatment of diseases that start at the molecular level.

“I don’t believe in eternal life, but if we could have a better understanding of our cells and the causes of aging, we may not need to fear disability and suffering toward the end of life,” Lindahl says. “That would be progress.”

Inspired by my father’s vision of a future when diseases we currently dread, such as cancer, may become manageable conditions treated by primary care providers, I reached out to experts in molecular biology, genomics, bioinformatics, oncology, salivary diagnostics and precision medicine for their insights into what I had learned in Stockholm. One person I spoke with was George D. Demetri, MD, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston and a professor of medicine at Harvard Medical School. Demetri’s research into molecular therapies for sarcomas, a subgroup of cancers, helped lead to the U.S. Food and Drug Administration’s approval of imatinib mesylate, one of the first drugs that can target a specific type of cancer cell and stop it from growing. He will present the keynote at the American Academy of Oral Medicine’s Oral Medicine and the Future of Health Care conference, scheduled this April in Atlanta.

“I would view this century as the one in which we finally get a handle on cancer in the same way that in the 20th century we got a handle on infectious diseases,” Demetri notes. When one thinks about how the development of antibiotics and vaccinations changed medicine from treating the consequences of infectious diseases to effectively stopping their spread in the first place, one can begin to imagine how the development of targeted therapies for diseases linked to DNA damage could change our entire approach to prevention and treatment.

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key takeaways

• Research demonstrates that DNA is not a stable molecule, as everyone had assumed. Instead, it is constantly breaking — but what makes life possible is there are chemical means by which the molecule repairs itself.
• If we can understand the mechanics of DNA, we could develop innovative ways to approach treatment of diseases that start at the molecular level.
• Pioneered at Stanford University, precision health is similar to the concept of precision medicine, but goes beyond the idea of personalized treatments to encompass personalized ways to predict and prevent disease development.
• The vision is for every health care provider to have access and contribute to a shared database of patient information that can yield insights into the best course of treatment for a given individual.
• A major evolutionary development in medicine is our ability to collect and analyze data on a sizable scale in order to predict disease. For the concept of “big data” to work optimally, however, dentists should be part of both gathering and using data for patient treatment.
• Many health care providers do not yet think of themselves as part of an interdisciplinary care continuum that encompasses every patient interaction with a provider. This mindset needs to change.

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DNA RESEARCH AND PRECISION HEALTH

One place this is already happening is at Stanford University School of Medicine, which last year launched an initiative it calls precision health. Precision health is similar to the concept of precision medicine, but goes beyond the idea of personalized treatments to encompass personalized ways to predict and prevent disease development.

By enabling the various schools and departments across Stanford University to work more collaboratively with each other and with clinicians in its hospitals and ambulatory care centers, Stanford officials hope to change the focus of medicine from advanced care for acute illness to disease prevention and management tailored to an individual’s specific genetic, environmental and lifestyle risk factors. Key to the effort is a new field called biomedical data science.

A founding member of the International Society for Computational Biology, Russ Altman, MD, PhD, is a professor of bioengineering, genetics and medicine at Stanford, and a leading precision health visionary. As he explains, the vision at Stanford is for every health care provider to have access and contribute to a shared database of patient information that can yield insights into the best course of treatment for a given individual.

Among health care providers, dental professionals would have a very important role to play because they not only tend to see patients more frequently than other primary care providers, they also have access to a wealth of potential patient information through examining the oral cavity. “I think the dental field is incredibly important,” Altman says, “because one of the windows to a patient’s molecular information is the oral cavity, with its epithelial cells and saliva.”

IMPORTANCE OF SALIVARY DIAGNOSTICS

Researchers are in the process of perfecting tools for analyzing bodily fluids for evidence of disease, such as DNA signatures of cancer and specific enzymes linked to inflammation. Saliva is a leading candidate among these bodily fluids because it can be collected easily, painlessly and without embarrassment, explains David Wong, DMD, DMSc, a professor and associate dean for research at the University of California, Los Angeles, as well as director for the UCLA Center for Oral/Head and Neck Oncology Research.

Wong’s research contributed to the National Institutes of Health’s classification of saliva as a diagnostic fluid similar to blood or urine. He and other researchers have identified genes and proteins in saliva that could serve as highly accurate markers for certain diseases and conditions, including various cancers. By conducting a panel of tests on saliva, it’s possible to detect diseases, such as lung or pancreatic cancers, that currently are very hard to spot at early and more treatable stages.

One of the windows to a patient’s molecular information is the oral cavity, with its epithelial cells and saliva

“In the next 20 years, precision medicine presents the opportunity to harness bodily omics information and utilize it to tailor treatment, detection and therapeutic monitoring,” Wong says. “And what better unit than saliva, assuming the foundation is there?”

In the future, dentists and dental hygienists may not be the ones who collect and analyze salivary samples because, in the vision of Wong, Demetri and others, this type of testing should be broadly accessible and possibly even fully automated via miniature sensors that can be placed on teeth to continuously send data to devices that can monitor for diseases. At the same time, the way dentistry is practiced could change based on salivary diagnostics and a new understanding of the biochemical mechanics of disease. For example, new insights into disease at the cellular and even molecular level could lead to innovative dental therapies.

“What I would like to see is dentists bringing forward the real challenges,” Demetri says. “In other words, what can the kind of insights that we are generating in cardiology and oncology do to fix problems dentists know about that we haven’t even thought of.” Noting that he personally has issues with plaque buildup, Demetri is hopeful that what he and his fellow cancer researchers are learning about the immune system and inflammation could lead to better treatments for conditions that dentists are expert in, such as periodontal disease. “While gingivitis may seem mundane compared to cancer, it is an enormous problem in terms of morbidity and the number of people affected,” he says.

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SIDEBAR: Could Dentistry Solve Precision Medicine’s Privacy Hurdle?

One of the main obstacles to a precise, data-driven approach to researching, managing and preventing disease is concern about data privacy. “Most of our challenges are not technical, but social,” notes Russ Altman, MD, PhD, a professor of bioengineering, genetics and medicine at Stanford University, and a founding member of the International Society for Computational Biology. “People are worried about the privacy of their data and who has access to it — and with good reason.”

The future of precision medicine that Altman envisions must rely on patients voluntarily sharing their personal information. It will not work if patients have no choice about whether their data is submitted to a central database and shared with other health care providers and researchers. “Everybody I know who thinks about this believes that the patient needs to be in control of the data,” he says.

To convince patients that it’s OK to share health data such as their own DNA sequence, it may help to study the example of dental records, explains George D. Demetri, MD, director of the Boston-based Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School. “We’ve seen a big public debate about genetic privacy, but we’ve all been identifiable by dental records for decades,” he says. “When there is a plane crash, the first thing authorities do is find the dental records to identify the victims. Why are people not scared about sharing dental records, or picking up on the fact that dental records are a wonderful complement to DNA sequencing and other personal health data?”

While there is a great deal of work to be done on the social and ethical fronts to arrive at a common under – standing about how and when personal health information should be shared, dental records are a great early example of what’s possible.

As Demetri notes, “While I respect the fact that information sharing has to be carefully watched, I’m optimistic that appropriate controls and consent can be implemented so that good things can come from this.”

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DENTISTRY’S ROLE IN PRECISION HEALTH’S FUTURE

Understanding the chemical mechanics of disease and corresponding development of precision medicine and precision health is truly an opportunity to bring dentistry to the forefront in medicine and primary care, according to Wong. An opportunity is not the same as a certainty, however. “If dentistry would like to be part of mainstream medicine, the burden is on us to demonstrate our value,” he says.

In precision health, one of the most valuable things a clinician can contribute is electronic data on individual patients. Alongside developments in biochemistry and molecular biology, including salivary diagnostics, a major change in medicine, Altman explains, is our ability to collect and analyze data on a scale that allows us to predict disease and keep people healthy. For the concept of “big data” to work optimally, dentists should be part of both gathering and using data on individual patients in a way that also addresses patient privacy issues. (See sidebar)

Many health care providers do not yet think of themselves as part of an interdisciplinary care continuum

“We can now imagine information systems that help practitioners — nurses, doctors and dentists — obtain access to relevant information and data in order to optimize care,” he says. “You can imagine that a dentist will not just look at a patient, but will look at a patient and then at a database where there are 100,000 others who have the same profile. The dentist will be able to see the outcome of different approaches to care so that personal clinical experience is not the only basis for a treatment plan, but, rather, the basis will include the global experience of tens of thousands of patients.”

Tailored approaches to medicine will not only pertain to complex diseases such as cancer, Altman explains. For example, we now understand that genetics and enzymes help determine how the body metabolizes pain medications. Yet there is also a strong mental component to pain perception, with people feeling more pain during times of stress or fear. A database of information might let a dentist accurately predict which patients may not respond as well to standard pain management. In turn, the experience of the dentist may help inform other clinicians about how to best manage pain in a particular patient, Altman explains.

“Dentists have a window into select medications and changes in medications that can affect oral hygiene,” he says. “They see the determinants of mood and markers of stress. They can get an estimate of the patient’s pain tolerance. An oral prophylaxis may reveal things with respect to the patient’s microbiome and general health. I think that if we have an integrated system for sharing information, what physicians learn could help dentists do a better job, and what the dentists learn could help physicians do a better job.”

Furthermore, dentists will play a vital role in checking the information other medical professionals may enter into a shared database about a patient. Numerous studies have shown that patients will lie to their doctors, Altman says — but they may tell their dentists the truth.

WHAT COMES NEXT?

Of course, there are significant barriers to allied health care providers sharing a single medical record. For one, dentists and physicians use different diagnostic coding systems; in addition, there is no electronic health record product built to serve both dentists and physicians. Even so, Altman, an expert in computational sciences with a doctorate from the Stanford Program in Medicine Information Sciences, believes the technology and programming challenges are quite solvable. The real challenges are cultural. Patients have an understandable concern about the privacy of their medical data. In addition, many health care providers do not yet think of themselves as part of an interdisciplinary care continuum that encompasses every patient interaction with a provider, including dental assistants, dental hygienists and physician assistants.

“I hope the precision health initiative will start to break down the barriers [between professions] and people will start to see the value of including all patient interactions and not just the limited and episodic interactions with physicians,” he says.

One place where this is happening is in cancer care, adds Demetri. Dentists have become more involved in cancer screening, and this helps illustrate how interdisciplinary teams are necessary for both the best research and clinical care. He receives many patient referrals from dentists, who also work closely with his team to monitor side effects from cancer treatment, such as tyrosine kinase inhibitors that bring a risk of oral complications.

“Cancer medicine is just the thin edge of the wedge of precision medicine,” Demetri says. “If you understand disease, just as when we understood the role of bacteria and viruses in infectious disease, we can target the fundamental pathogenic mechanisms. Are we going to get rid of cancer in 100 years? Probably not entirely, but my hope is that our kids’ kids will not fear cancer the way we do today. We have never seen a time with more promise than now. Every day, we love going to work because we never know what we are going to discover, and we never know what rock we are going to turn over and see something nobody has seen before.”

It is a future my father, who is 78, realizes with some regret that he will miss. He often says he wishes he were 30 years younger because “now is when things are really getting interesting.” As discoveries begin to transform clinical practice, there will certainly be exciting changes in our approach to dental treatment. Despite our propensity to fear change, my father reminds us to be open minded, because we are lucky to witness the next historic transformation in health care play out — a future in which precision health allows clinicians to predict and prevent or treat disease before it impacts quality of life.