Dr. Joan Bull–Recipient of the 2008 Robinson Award

Energy and persistence conquer all things.

Benjamin Franklin

I frequently find myself telling new PhD students that persistence, and the energy needed to sustain it, are two of the most important traits for a successful career in medical research. Students often seem surprised by this, thinking that grades, lab bench skills and research topic are the most important criteria for success. However, they soon come to realize just how difficult it is to be persistent and energetic when their project is not going well, the hypothesis fails or an experiment cannot be repeated. Persistence is especially revealed when an individual has an idea that is counter to that of the majority opinion in a research field and yet pursues that idea with enthusiasm until success is finally achieved. When I envision the personification of persistence and energy among members of our field, I think of Dr. Joan Bull. Thus, it is truly an honor for me to be given the opportunity to describe here for readers of the International Journal of Hyperthermia the achievement for which Dr. Bull was recently recognized by her colleagues in the Society of Thermal Medicine (STM) who voted her the recipient of the 2008 Eugene Robinson Award, our Society's highest honor.

I believe that although we are recognizing Joan for her academic accomplishments and scientific discoveries, she considers herself first and foremost a medical oncologist who cares most deeply about her patients. Her most important goal has always been to use her research skills to reduce pain and suffering resulting from cancer and to minimize the normal tissue toxicity that results from chemotherapy. Her unwavering persistence in pursuing this goal has resulted in her becoming both an outstanding clinical and laboratory scientist, an uncommon achievement because of the extraordinary energy required for excellence in each. Her implementation of multiple investigator-initiated Phase I and II trials as well as her 130-plus academic papers and invited reviews are an amazing testament to her productivity, expertise and energy. In a recent discussion with me, Joan commented that her interest in reducing nausea during chemotherapy began during the days she led the first large trial of MOPP (a combination of nitrogen mustard, Oncovin (vincristin), Procarbazine, and Prednisone) and radiation for Hodgkin's disease while she was still only a fellow at Stanford. At that time, Joan and her colleagues were greatly encouraged by the clinical data of DeVita and Carbone and others at the National Institutes of Health (NIH) on the use of MOPP for patients with Stage IV Hodgkin's disease. Since Joan did all of the chemotherapy injections herself (and reminded me that in those days, ‘there were no chemotherapy nurses’) she was especially affected by the intense suffering from nausea her patients experienced. Thus, as a very young doctor, Joan was determined to make things better. Subsequently, she entered a second fellowship at NIH (where she had the opportunity of working under the leadership of Dr. Paul Carbone), and directed the first randomized study that identified CAF (Joan noted to me that ‘in Texas, it is known as FAC’) which is cyclophosphamide, adriamycin and 5-FU. CAF is still standard therapy in both primary breast and metastatic breast cancer. Luckily for those of us in the Society for Thermal Medicine, during these days Joan's attention was captured almost exclusively by hearing about thermal therapy. At that moment, her life's goal seems to have crystallized: to use hyperthermia to improve the anti-cancer efficacy of chemotherapy while reducing normal tissue toxicity. In this field, she became a pioneer, someone who has conceived of and developed fundamental new ideas.

While there are multiple reasons to honor Joan, including her extensive work combining thermal therapy with chemotherapy, the Robinson Award was primarily given to honor her early recognition of the value of systemic thermal therapy–heating the whole body to achieve improved efficacy of chemotherapy. While others were also early proponents of this approach, Joan demonstrated remarkable persistence - her interest in this approach (and improving it) has been continuous, from her medical fellowship days at the NIH to the present day where she is running Phase I and II trials using whole body hyperthermia that continue to push the envelope of cancer care. In the early days of hyperthermia, when Joan was working hard to validate the systemic heating approach, most of the field was working toward development of localized heat treatments, and designing methods to focally deliver heat and monitor temperature. There were many STM meetings (or North American Hyperthermia Society in these days, or Radiation Research meetings) where Joan was the only person on the clinical program who spoke on the use of whole body hyperthermia. But, perhaps even more importantly, through her continuous efforts, Joan is also responsible for spearheading a major paradigm shift in the use of whole body hyperthermia - she challenged the concept that hotter is better, and argued convincingly that a mild temperature (e.g. 40°C) is better for combination with chemotherapy. In 1994, Joan and her team published the first of many papers on the concept of ‘Low Temperature, Long Duration’ whole body hyperthermia [1], which she found in rat tumor models to improve the efficacy of chemotherapy without increasing its toxicity. She also noted that these milder temperatures could be helpful in stimulating the immune system. And, like the true translational scientist that she is, clinical trials to test this assumption in patients soon ensued. Exciting new data has emerged and is emerging supporting the efficacy of this approach (now often referred to as ‘fever range whole body hyperthermia’). The success of these clinical trials, and exciting new pre-clinical information is now emerging in published form.

Joan Marie Carlson Bull was born in Dayton Ohio but her family moved to Northern California (Vallejo, CA) when she was just six months old, and she grew up a true Californian, attending Vallejo Elementary School, Junior High and High School. She next attended UCLA and was then accepted to a prestigious five-year medical school program at Stanford. Joan did her Internship at the University of Chicago, and then returned to Stanford for her Residency and Fellowship. She eventually left California for a second fellowship at the NCI and then moved to Houston where she has developed both a laboratory and clinical research program. Joan has spent most of her professional career juggling multiple responsibilities, rising through the ranks at the University of Texas Medical School, where she is currently a tenured Professor of Medicine. She also has appointments at the Hermann Hospital and the Lyndon Baines Johnson General Hospital. She has been an active and dedicated member of the Society of Thermal Medicine from its inception (as North American Hyperthermia Society). She has been a council member several times, and served as President in 1996. She is also an active member of ASCO and AACR, having served on multiple committees. Impressively, she has won Teaching Excellence awards multiple times. She has served on several NIH study sections, including serving as a member of the Radiation Study section and several different breast cancer study sections for the Department of Defense. During these years, Joan also raised two children - a significant part of this as a single parent. Her son Todd Bull, MD, is now an Associate Professor in Pulmonary Medicine at the University of Colorado. He is director of the medical ICU and also has a productive, funded laboratory that investigates the molecular biology of pulmonary hypertension. Her daughter, Lara Bull, PhD, received her doctorate in Epidemiology from the University Of Texas School Of Public Health, and is currently a Post-Doctoral Fellow in the Human Genome Sequencing Center at Baylor College of Medicine. Joan also has two step-daughters, Courtney and Ashley, who followed their father with careers in business. Courtney is a Vice President of a well known investment banking firm in NYC, and Ashley is in charge of worldwide sales operations for a large software business in Houston. Joan's husband, Philip Tuttle, is an international venture capitalist and investment banker.

Joan's recognition as the Robinson Awardee is very special to me personally since she is one of the first people I met when I joined our society and she is responsible for several critical decisions that I made in my own area of research on cell biology and immunological effects of hyperthermia. I first began thinking about hyperthermia during a period I spent working in the Radiation Medicine Department at Roswell Park Cancer Institute. At that time, in the early 1980s, Dr. Richard Johnson was the Chair. Dr. Johnson had worked in hyperthermia earlier and became very interested in the work Joan and others were doing at the NIH on whole body heating and how it might be used. Much of his interest in whole body hyperthermia, which he shared with me and my husband, was based on Joan's work and enthusiasm for the field, including her 1982 review [2] on the possible role of whole body heating on physiological and immunological parameters. After national meetings, these thoughts were often discussed with everyone in his program at Roswell Park and he eventually assembled a sauna in the radiation clinic as a means of applying whole body heating with the belief that achieving mild fever-like core temperatures had beneficial immunological effects. I did not meet Joan personally until I attended my first hyperthermia meeting in 1994 with a poster on the effects of fever-range heating on lymphocyte activation and distribution of cytoskeletal (spectrin) proteins. To my surprise, she had not only read my abstract but had left a note on my poster asking to meet with me! Although I was not a speaker, she was excited and supportive of the mild whole body hyperthermia work we were doing. She spent a lot of time at my poster, encouraged others to stop by to read it, and told me about her new work on a low temperature, long duration heating protocol and its anti-tumor effects; I remember feeling astonished about the implications of her work on our own. A short time later, Joan became directly involved in helping my colleague at Roswell Park, Dr. William Kraybill, to establish the same clinical heating protocol that she had developed for her patients in Texas. She spent many hours giving us advice on instrumentation and shared her own experience with whole body heating of patients, saving us years of work. In 1999, I was invited by Joan to give a seminar at her institute and I agreed to accompany her through her clinical day, up until the time of my seminar later in the afternoon. This is when I learned a good lesson about her energy, drive and persistence. Joan's day began at 6 am with patient rounds at Memorial Hermann Hospital along with a group of residents and fellows she supervised. Many of the patients were in advanced stages of their disease, (who were being evaluated for placement in one of multiple various Phase I trials in the department, including whole body hyperthermia), and I was very impressed with the individual attention and time Joan gave to each patient. At 7 am, Joan ran a highly intense review with all of her medical fellows, sharply interrogating their summaries of multiple patients, while I watched and ate some of the breakfast she had brought for everyone. At 8:30, she had a lab meeting with her dedicated laboratory staff (where I met Rick Strebel who later gave me an actual demonstration of the use of ‘rat hammocks’ for warm water immersion needed during the mild whole body hyperthermia/chemotherapy experiments). At the end of my visit, Joan made dinner at her lovely (and fascinating) home, filled with wonderful art and plants, and quite an eclectic collection of souvenirs from the travels of Joan and Philip. I also met her daughter Lara, then a student at Rice University (and now an accomplished molecular epidemiologist). Joan spent many hours of her time with me that day, and at the end, I learned that she had an NIH grant due the next day! She had pulled an all nighter the day before, and would do it again after I left.

In summary, it is simply not possible to think back upon any of our annual hyperthermia meetings in the last many years without recognizing the persistence, amazing energy and total commitment of Dr. Joan Bull. Her belief in the power of systemic hyperthermia as a component of cancer treatment is truly inspirational. Excitingly, there are more and more publications and abstracts on the use of milder hyperthermia protocols for cancer therapy at each annual meeting, and we all owe a debt to the pioneering efforts of Joan Bull. Her energy is infectious as she speaks on the stage (even her slides are highly dynamic) or when she is zooming from session to session, or when she is simply asking critical questions, reminding us all that we are doing it for the patients. Indeed, we have been very fortunate to have Joan Bull as our colleague and we are grateful to her for her seminal discoveries and her persistence and her energy that will undoubtedly help us significantly improve cancer care in the twenty-first century.

Elizabeth A. Repasky