Approximately 43 million Americans suffer from arthritis and related diseases. That's almost one out of every six people.

The disease comes in 100 different forms, all of which involve the inflammation of one or more joints. It can be painful and debilitating. But thanks to a rich tradition of outstanding researchers at Duke University Medical Center (DUMC), many new treatments are available to help manage the disease.

May is National Arthritis Month, a designation started by the Arthritis Foundation in the last decade to bring attention to this crippling disease. But long before there was a National Arthritis Month, Duke doctors were hard at work looking for ways to control the ailment.

These pioneers developed groundbreaking treatments for arthritis and increased understanding of the disease. They also laid the foundation for subsequent and current research at Duke, which has cultivated a research environment that has attracted the best and brightest researchers in the field.

"It is that reputation for excellence that has allowed Duke to attract the top-quality researchers who are leading the way nationally in arthritis treatments," says Barton Haynes, MD, chair of the Department of Medicine and an internationally renown arthritis researcher.

A Rich Tradition
Duke's storied involvement with arthritis research began more than 40 years ago when Nobel Prize winners George Hitchings and Gertrude Elion, scientists with the pharmaceutical company Bourroughs Wellcome, searched for drugs to reduce the toxicity of immunosuppressants used in kidney transplantation.

During their search, the team discovered that Allopurinol, a drug developed for cancer treatments, lowered blood uric acid levels. It was a significant finding for sufferers of gout, which is caused by crystals formed in the joints when blood uric acid levels rise too high.

R. Wayne Rundles, MD, a young member of DUMC's faculty, took that discovery and with equally young colleagues James Wyngaarden, MD, and Hal Silberman, MD, pioneered the development of Allopurinol for the treatment of gout.

Rundles went on to become chief of hematology/oncology at Duke University Hospital. Wyngaarden became chief of rheumatology and established a laboratory to study purine metabolism, the process that makes uric acid. Wyngaarden, together with William Kelley, MD, (who became chief of the rheumatology division after Wyngaarden) and Edward Holmes, MD, (who became chief of endocrinology) formed a trio that led the way nationally in the field for almost 20 years.

Wyngaarden eventually left Duke to serve as the director of the National Institutes of Health from 1982 - 1989. He also worked in the White House Office of Science and Technology before returning to Duke as director of the Human Genome Organization and vice chancellor for Health Affairs.

Then came Ralph Snyderman, MD, previously a researcher with the National Institutes of Health, who succeeded Kelley as Duke's chief of rheumatology; under Snyderman's leadership it was renamed the division of rheumatology and immunology. Snyderman is now chancellor for Health Affairs at Duke University and president and CEO of Duke University Health System.

As a researcher, Snyderman's main focus was on the mechanisms of inflammation. Early in his career, he discovered a specific complement component (C5a) that mediates acute inflammation. He has been a major figure in defining how white blood cells respond to inflammatory signals. Snyderman's contributions to the understanding of inflammation led to worldwide recognition, including the lifetime Achievement Award from the Arthritis Foundation, Eastern Region.

Haynes, who became the next chief of rheumatology, also has received international acclaim as an arthritis researcher. A recipient of the Arthritis Foundation's prestigious Howley Award in 1995, and the American College of Rheumatology Distinguished Scientist Award in 2002, Haynes was the first to describe the role of certain molecules found in the blood in the inflammation process. He also developed a model in which human tissue from a joint is implanted on the kidney of an immunosuppressed mouse to study the effects of different drugs on joint tissue.

Haynes' work has led to several new treatments for arthritis in the past five years.

The current division chief, David Pisetsky, MD, PhD, who also serves as director of Duke University's Arthritis Center, is a world expert on the role of the immune properties of DNA and how this molecule can induce antibodies in the autoimmune disease of systemic lupus erythematosus (commonly called lupus). When Pisetsky also received the Arthritis Foundation's Howley Award this year, Duke became the first institution to have won this competitive and coveted award twice.

A New Generation
The work of all these scientists not only has changed the way the medical profession views and treats arthritis, but is lighting the way for a new generation of Duke researchers.

For example: Virginia Kraus, MD, PhD, a Duke researcher involved in an extensive study to map disease predisposition for arthritis, explains that until five years ago, many people considered osteoarthritis (the most common form of the disease) to be an inevitable consequence of aging. But it is now known that in a majority of cases, the ailment is hereditary.

"People think that if something is hereditary, you can't do anything about it. But that's not true," she says. "There are many hereditary conditions such as cystic fibrosis that can be treated. Once you understand the causes, you can target the therapy."

Other Duke arthritis researchers, Farshid Guilak, PhD, and his wife, Lori Setton, PhD, are working to learn how to grow new cartilage for joint repair using stem cells from body fat and novel biodegrad-able scaffolds.

"Now someone who has severe arthritis ends up with a total joint replacement," Guilak explains. "We are working toward living tissue replacement of cartilage and bone."

Guilak joined the Medical Center faculty and Setton joined the Biomedical Engineering Department eight years ago because Duke was one of the few places equipped to handle their research in bioengineering.

"Most places either had a great medical school or a great engineering school," Guilak says. "Duke was one of the few places that had both."

Pisetsky says that Duke's reputation for excellence is what appealed to him. The chance to work with scientists of the caliber of Wyngaarden, Holmes, and Snyderman made the choice of where to do his research an easy one.

"These are top-flight physician investigators, top-flight scientists who at the same time are committed to excellent clinical care for patients and teaching," he says. Working with these people, "You learn how to do things. You learn how to ask questions in a different way that ultimately leads to success."

Trained at Duke
Many of Duke's finest doctors came to the university as trainees. Seventy percent of the faculty in the Department of Medicine trained at the university, Haynes says.

Kraus was one of those homegrown stars. A Duke medical student, she stayed for her residency, a fellowship in rheumatology, and a doctorate degree. She left briefly to see what else was out there, but returned to Duke satisfied that she had found the best spot for her research.

"One of the great strengths has been the caliber of colleagues," Kraus says. That's a sentiment echoed by Guilak, who says that his colleagues not only are exceptionally knowledgeable but also are unusually accessible. "Everyone here is so easy to approach," he adds. "It is easy to draw on the expertise of others."

That interaction has led to numerous collaborations across departments, Guilak says. One of those partnerships has been between his team and Pisetsky's. Guilak's research originally focused solely on osteoarthritis, while Pisetsky dealt with rheumatoid arthritis. Together they have found numerous links between the two.

Haynes, who is stepping down from his current position as the chair of the Department of Medicine to head Duke's Human Vaccine Institute and become a program director at the Institute of Genome Science and Policy, says the "future is very bright" for the work being done at Duke.

Pisetsky agrees: "This is one case where the research has already paid off. There has been a lot of improvement. People are hopeful that this pace will continue because as much as we know, there is still a lot more to learn."