The Division's 50th Anniversary Celebrration
The University of Washington Division of Rheumatology celebrated its 50th Anniversary during the National ACR Meeting in San Francisco on October, 26th, 2009. The event was attended by more than 60 current and former trainees as well as clinical faculty and colleagues associated with the Division.
Keith Elkon, Division Head since 2001, welcomed the participants and gave a brief history of the Division. Excerpts of his talk as well as Ken Wilske, one of the first fellows in the Division, and Mart Mannik’s, Division Head for 34 years, are included in this newsletter. Future newsletters will include reflections by Gordon Starkebaum and Robert Willkens and thoughts about the future of UW Rheumatology by Jeff Ledbetter and fellows in the program.
Keith Elkon , MD, Head, Division of Rheumatology, UW
The first Division Head appointment was John Decker. John was literally a giant in Rheumatology ~6 ft 4. Coming from Walter Bauer prestigious group at Mass Gen, John started up the Division in 1958 and left in 1965 to become the Chief of the Arthritis and Rheumatism Branch of the National Institute of Arthritis, Metabolism and Digestive Diseases. In 1983 Dr. Decker was appointed the Director of the Clinical Center of the NIH.
Bob Petersdorff went in search of a new Division Head. His search ended at the Rockefeller University where he sought out Mart Mannik who was then one of Henry Kunkel’s rising stars. Petersdorff chose wisely as Mart went on to lead the Division for the next 34 years and build it into one of the premier programs in the country that trained many or most of you in this room this evening. Now, of course Mart could not have done that alone. There are 4 more rheumatology giants who served for a remarkable 30-50 years and I would like to pay tribute to the former Section Heads Bob Willkens at HMC and Gordon Starkebaum at VA and to Bruce Gilliland and Peter Simkin who served as exemplary teachers and role models. Sadly, Bruce passed away in February, 2007.
Talking about the present and future of the Division, Keith Elkon mentioned that “a very generous estate gift by Lucile Henderson allowed us to create 3 professorships that honor Mart Mannik (I am fortunate to have the Mannik-Henderson Professorship), a Gilliland Professorship that was awarded to Greg Gardner, the Clinical Director of the Division. Greg has been a remarkable clinician teacher and the Division is most fortunate to have him. The 3rd Professorship Willkens-Henderson is yet to be awarded to a new Section Head at HMC.
Best of all, the estate gift has allowed us to build the division. We are thrilled that Grant Hughes has just been recruited as Assistant Professor of Medicine in Physician Scientist pathway and Jeff Ledbetter has been recruited as a Professor in the Division. Jeff, together with Peter Lindsley discovered CTLA-4-Ig /Orencia. They then collaborated with Dave Wofsy right here in San Francisco using the first biologic to successfully treat murine lupus. Since that time, Jeff has devoted most of his career to translational research and has been instrumental in generating many other biologics. Jeff continues his efforts to develop new therapeutics for autoimmune diseases in the Division of Rheumatology”.
Ken Wilske, MD, clinical Professor, UW
My fellowship in rheumatology at the University of Washington, 1962-1964, centered on not only learning the background of rheumatology but recognizing and describing rheumatologic diseases in patients and their complications (leg ulcers, destroyed joints, disability) and complications of therapy–primarily high doses of aspirin—many side effects, little therapeutic effect. Subsequent therapies included the introduction of NSAH) and early DMARD drugs. Again, much effort was spent in recognizing complications of therapy with targets hopefully of 20% therapeutic improvement.
Modern treatment entered the picture in the late 80’s with combination therapy with DMARD drugs–particularly methotrexate with subsequent introduction of the biologic response modifying drugs. A limitation of therapy to this point was the “therapeutic pyramid”, starting at the low levels with aspirin or NSAID drugs and working up the pyramid to the most effective drugs, a time period usually taking 3-5 years.
With the increasing awareness of a 2-year therapeutic window, subsequently revised to a 6-month window, it was my feeling then that treatment of patients with rheumatoid arthritis should be with a new paradigm: “inverting the therapeutic pyramid with early induction and step-down therapy”. This early induction therapy directed toward control of inflammation and resetting the inflammatory rheostat with biologic response drugs in combination with methotrexate with subsequent step down to less toxic and less expensive drugs to control disease activity has now allowed us to aim at and achieve a 70-80 % therapeutic improvement, particularly if treatment is started early.
The future of this journey appears bright with rheumatologists becoming specialists in therapy of “IMID” (immune mediated inflammatory diseases). The musculoskeletal portion of the practice will probably shrink to less then 50% with the remainder of the patients being seen for “EV1ID” diseases of the eye, ear, lung, cardio-vascular system, kidney, bowel, etc.
My journey in rheumatology has been stimulating and marked by great improvement in our therapeutic success. The future appears even brighter and more stimulating with application to many “TMID” diseases, including cardiovascular disease.
Mart Mannik, MD Professor Emeritus, UW
After my arrival, the Division expanded by establishing sections of the Division at the other major teaching hospitals of the School of Medicine. The Section of Rheumatology at the Harborview Medical Center was formed in 1967 with Dr. Robert Willkens as Head of the Section. The Section of Rheumatology at the Veterans Administration Medical Center was established in 1968 with the recruitment of Dr. Bruce Gilliland as the Head of the Section. He was followed by Dr. William Arend and then Dr. Gordon Starkebaum in this position. The Section of Rheumatology at the Pacific Medical Center was established in 1978 with Dr. Woodruff Emlen as the Head of the Section. The Division gained additional laboratory space at the School of Medicine.
The Division was successful in recruiting talented physicians to the fellowship program. A number of these fellows became independent investigators and faculty members with their own support for research. These individuals included Drs. William Arend, Richard Pope, Roger Hollister, Alan Haakenstad, Woody Emlen, Gordon Starkebaum, Francis Nardella, Joyce Gauthier, Lee Nelson, and Eric Sasso. The number of full-time faculty members varied from year to year, eight being the highest number. The Division gained local, national and international recognition. A large and dedicated clinical faculty of the Division assisted the teaching of students, interns, residents and fellows.
Leading the Division for 34 years was a gratifying professional experience. It was highly exciting to see research results that matched the predictions in a grant application. Enjoyment and pride was provided in seeing young physicians succeed in their research or achieving their career goals. Seeing patients respond to recommended treatments provided professional satisfaction. I enjoyed my career and had no regrets in choosing a career in academic rheumatology.
Robert Willkens, M.D., Professor Emeritus, HMC
When I joined the Department of Medicine in 1958, there was no Division of Arthritis. As a matter of fact, as late as 1974 I gave a talk entitled “Who and what is a Rheumatologist?” Many of you answered that question by your clinical and investigative activities that incorporated immunology, pharmacology, biochemistry, and genetics into the merging discipline of rheumatology. Many of you are in fact role models and have attracted young physician scientists into this discipline. As outstanding members of this division, by your activities you have expanded the breadth of Rheumatology. You have helped to define those processes that lead to disease and disability.
I would like to mention you all by name and recite your accomplishments that have led to better understanding and management of rheumatic disease. Your achievements have been incorporated in the literature and will be remembered in perpetuity.
I am immensely proud to have been associated with this division throughout my career and to have served the institution of Harborview Medical Center during this time. I admire and envy your continued involvement in this pursuit, for I anticipate further progress that will allow the cure of those disorders that we pioneers found so mysterious.
Catherine Bakewell, M.D., 1st year Rheumatology Fellow, UW
Regarding the future of rheumatology, I can honestly say I don't know. But I do know this is an exciting time – the entrance of the biologics onto the world stage within the last 10 years revolutionized the field and drastically changed expectations of outcomes, giving us as physicians the satisfaction of offering many of our patients normal, fully functional lives. Plus many of the arthritic diseases are still not adequately understood, offering those who do research the opportunity of discovering something that will make a real difference. Just on Saturday Dr. Antony Rosen from Hopkins talked to us in the review course about several new antibody/antigen combinations implicated in myositis which had previously been unknown. Where I had previously known only about anti Jo-1 (antibodies against histidyl tRNA synthetase), now we have PL-7, PL-12, OJ, KS, and EJ (antibodies against 5 other tRNA synthetases), rounding out the picture for those who clearly were suffering from ‘antisynthetase syndrome' but were anti-Jo1 negative. It is possible to envision a time in the not-so-distant future where many now unexplained autoimmune syndromes have precisely defined mechanisms and very specific treatments. Around the globe scientists are investigating gene therapy, including targeted gene therapy in arthritis, and this may be the next series of revolutionary treatments to enter our armamentarium.
As for why I went into rheumatology, I do not consider myself any different from the rheumatology fellows around the nation. Dr. Kolasinski gave us a talk on Friday night, and she published with the ACR in 2007 the results of a nationwide survey of rheum fellows as to why they chose their subspecialty. It showed that the majority of rheumatology fellows had their initial exposure to rheumatology as second-year and third-year medical students, and >75% solidified their decision during internship and residency. The most influential factors in this decision were clinical rotations in rheumatology and exposure to role models and mentors. This was followed by a particular patient exposure, family member, research, and at the bottom of this list, was a lecture. So for me, it was working closely with Dr. Greg Gardner on the musculoskeletal rotation (which ironically was a rotation reserved for residents destined for primary care) that really both piqued and solidified my interest in rheumatology. The disease processes were interesting, I liked the idea of the continuity of care with a specialized focus, and I thought that if all rheumatologists were like Dr. Gardner it would be a great field to work in. In fact, I do believe this program is blessed with outstanding and kind physicians, and I have enjoyed working with all the faculty at UW. But I do think that Dr. Gardner deserves special mention here, he has never wavered in his dedication to his patients, students, residents or to us his fellows, and I think I speak for all who know him when I say -- you are awesome, you are shaping the future of rheumatology everyday.
Gordon Starkebaum, MD, Rheumatology Section Head, VA SPA
Bruce Gilliland was the first section head of Rheumatology at the Seattle VA Medical Center in approximately the years 1968 through 1971. In 1971 he moved over to the university to become Acting Head of the Medical Resident Program. This was the first of multiple moves that Bruce made over the ensuing years, including becoming Chief of Medicine at Providence Medical Center for a number of years and, briefly, Acting Dean of the School of Medicine following Dr. David Dale’s resignation. It is interesting that Dr. Gilliland worked with Dr. Robert Evans, for whom the Evans Syndrome is named, namely autoimmune hemolytic anemia and autoimmune thrombocytopenia. Bruce described a syndrome of Coombs-negative immune hemolytic anemia and developed a sensitive assay to measure red cell IgG for levels that were below those detected by the standard Coombs Reagent.
Bruce was succeeded by Dr. Bill Arend, who became the head of Rheumatology in 1971, or thereabouts. Bill had been one of Mart’s Fellows and worked on immune complex models of disease. In those days, the usual model was human serum albumin and anti-HSA antibodies which were raised in rabbits. These immune complexes were studied both in vivo, injecting in mice and other animals, as well as in vitro. Bill was interested in their interaction with human immune cells, in particular with monocyte-macrophage cells. He developed a technique to purify human peripheral blood monocytes using adherence in vitro. He was studying uptake and reactivity of human peripheral blood monocytes to these immune complexes when he noticed that the response appeared to be dampened and less than expected in certain conditions. From this he eventually deduced that an inhibitor of a newly emerging cytokine, named IL-1, was likely to be involved. After he moved to Denver in 1980, he then pursued this hypothesis which eventually led to the cloning of the IL-1 receptor antagonist and subsequent development of the drug, Anakinra.
I was Bill’s first Fellow at the VA, starting in 1975. After trying to work with monocytes for some time, I chose to work with cells that were far easier to purify, namely peripheral blood neutrophils. And in the tradition of Bruce Gilliland and Bill Arend, I studied the interaction of these cells with immune complexes in vitro and in some cases in vivo. My first Fellow at the VA was Dr. George Saari, who had been a classmate of mine at Columbia and had spent 3 years in the Indian Health Service prior to becoming a rheumatology fellow. George spent one year studying in Norway with Dr. Jacob Natvig, and he spent his second year at Seattle VA.
During those early years, as Fellow and career development investigator, I had the privilege of working with a number of my contemporaries at the University, including Alan Haakenstad, Joyce Gauthier, Fran Nardella, and Lee Nelson. Carol Ragsdale was actually a pediatric rheumatology Fellow who worked in Dr. Arend’s laboratory. Carol was a delightful person who introduced me to the books of John LeCarre and Vladimir Nabokov. My mentors included Dr. Mannik as well as Bruce Gilliland, Peter Simkin, Andy Healey, Bob Willkens, and Ken Wilske. During my years at VA Puget Sound, I trained 9 Fellows, many whom have gone into practice in the Seattle area, including George Saari, Susan MacKinnon, Neal Nygard, Christi Kenyon, Nancy Shasteen, Pam Sheets, Therese Dawson, Nimali Mendis, and Mary Wemple.
After Bill Arend left the VA in 1980 I became the Acting Head of Rheumatology, and then the Head of Rheumatology in 1981.
After I became Chief of Staff in 1999, Dr. Andy Luk became the head of the arthritis section at VA Puget Sound in 2001. Shortly after Andy came, Dr. Mannik stepped down and Keith Elkon assumed the reins as the division head. During this time we instituted the change that during the first year all the Fellows would rotate to the VA and begin research projects at the University during their second year instead of having the VA Fellows spend the entire 2 years at VA. With the departure of Dr. Luk in November 2008, I have become Acting Head of Arthritis at the VA Puget Sound and I hope to become permanent Head of Arthritis beginning April 2009.
I should mention and mourn the death of 3 colleagues who worked at the VA Arthritis service including Bruce Gilliland, George Saari, and Carol Ragsdale.