The story of modern cancer therapy would not be complete without the inclusion of the work of Paul Calabresi and some insights about the challenges he faced, along with his accomplishments.
For this chapter in the “Cancer History Project”, I revised and extended a Memorial I wrote for Paul in 2006. I also had the pleasure of interviewing many who knew him well including his children: Steven Calabresi, Janice Calabresi Maggs and Peter A. Calabresi, MD. Others gave generously of their time to speak with me and share stories and experiences which I hope will add some richness to Paul’s contributions as an oncologist. They included Dr. Roy Herbst, Ensign Professor of Medicine (Medical Oncology), Professor of Pharmacology, Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital and Associate Cancer Center Director, Translational Science, Dr. Edward Chu, Director of the National Cancer Institute-designated Albert Einstein Cancer Center, Vice President for Cancer Medicine at Montefiore Medicine, Professor of Medicine and of Molecular Pharmacology and Roger Einiger Professorship of Cancer Medicine at Einstein, Dr. Vincent DeVita, Amy and Joseph Perella Professor of Medicine at the Yale Cancer Center, Professor of Epidemiology and Public Health at Yale and Former Director of the Yale Cancer Center and Dr. Thomas DeNucci, Medical Director, Rhode Island Hospital Endoscopy, Gastroenterologist at Lifespan Physician Group and a Clinical Associate Professor of Medicine at The Warren Alpert Medical School of Brown University.
Paul Calabresi was born in Milan, Italy on April 5, 1930. He was the son of Dr. Massimo Calabresi and Bianca Maria Finzi-Contini Calabresi. In Europe, his family was active in the anti-fascist resistance but in 1939 fled to the United States.
Paul’s parents told the story of Paul’s arrival to America. He was literally the first one off the boat and ran down the gangway. He spread his arms wide and shouted, “I am an American boy now!” The family moved to New Haven where his father joined the faculty of Yale University School of Medicine as a cardiologist at the Veterans’ Administration Hospital. Paul’s mother was a scholar of European literature, earned a Ph.D. in French at Yale and was Professor of French and Italian at Connecticut College and for many years Professor and Chair of the Italian Department at Albertus Magnus College.
Paul excelled in school but truly loved being a Boy Scout where he earned the rank of Eagle Scout. He was happily selected to raise the American Flag at the start of every meeting. He was proud of his Italian heritage but so very proud of being an American. Paul attended the Hopkins School in New Haven and then received his bachelor’s degree and then his MD degree from Yale University. He served his internship on the IV (Harvard) Medical Service, Boston City Hospital. For the next four years he became a field investigator for the National Cancer Institute as a project associate in the Department of Medicine at the University of Wisconsin. He returned to Boston City Hospital for another year of residency and then joined Yale University as a research fellow. Paul rose through the ranks at Yale until 1967 when he was promoted to Associate Professor of Medicine and Pharmacology and coordinated cancer training for internal medicine at Yale. He spent a year at the University of Lausanne in Switzerland as Visiting Scientist and then returned to Yale as Associate Professor of Medicine and Pharmacology.
He was recruited by the fledgling Brown University Medical School to be Professor of Medicine in 1968, based at Roger Williams Hospital where he became Brown’s first Chairman of Medicine in 1974. He was also the first medical oncologist in the U.S. to achieve this status. He served as Brown’s Chairman until 1993, but in 1991 while continuing his research and patient care, transferred his base of operations to Rhode Island Hospital.
He blended his professional and personal lives in a fashion that his children marveled at. He was present and engaged during all minor and major family trips and events but always brought up scientific and patient care issues which were challenging him and his colleagues. While some today might believe that this would inevitably lead to “burnout” because of his inability to relinquish “his work-self” when with his family, for Paul it led to a harmonious blending, and benefits were evident for him and participants in both venues. He had a holistic approach to medicine and life.
Wolfgang Oster, formerly on the faculty of Brown University and a leader in biotechnology, (soon to be the CEO and Chair of ELOS Oncology Inc.) said the following about Paul: “Paul was a special force, a brilliant physician with amazing judgment. I couldn’t have found anyone better to mentor me, both for my business career as well as for my private life. He loved Europe and he adored Italy. ‘Parla Italiano?‘ was something he loved to ask. I walked with him in Pisa in the area of the Leaning Tower and it was a beautiful Italian night. He said, ‘Do you know what makes these Italian nights so special,’ and, he continued, ‘because you can’t feel them, they are like part of you.’”
His wife, Celia, an occupational therapist and the love of his life, was the family’s guide and protector. She ensured that, when Paul’s attention needed sharp focus, as when sailing through difficult waters, he was a safe and careful navigator. Paul and Celia spent 49 wonderful years together. Celia was always a partner in all of Paul’s many activities and whose love of travel and their family was unparalleled. Celia passed away in 2018.
Paul was a good Samaritan. He believed that it was an honor to be a physician and with that came a duty to serve others in all circumstances. As a child, Steven Calabresi saw firsthand, his father in action. A skilled sailor, if Paul would see a craft in distress, his boat would assist or remain close by until the Coast Guard arrived. An avid and skilled skier, Paul was the first one at the side of an injured person and waited for and accompanied the ski patrol as they tended to that individual. Paul was also the first one to come forward on an airplane flight if a doctor was needed. Paul was with his family at a beach when he was informed that a child had a fishhook which penetrated his scalp. Paul responded immediately and rode in the ambulance to make certain the boy was safely transported to the ER.
Widely regarded as a “statesman of oncology,” Dr. Calabresi was at the forefront of oncology therapy and also worked with the American Board of Internal Medicine, helped to carve out oncology as an important subspecialty and was instrumental in developing training programs throughout the United States.
One of Paul’s major contributions was in understanding and further elucidating the pharmacology of cancer chemotherapeutic agents—how the body processes and metabolizes them. He had typhoid fever as a child and recovered. His children believed that this may have stimulated him to find medications to eradicate cancer cells the way antibiotics killed the bacteria and saved his life. He was also an early supporter of combination chemotherapy as well as combined modality therapy, interdigitating surgery and radiation therapy with chemotherapy in a safe and effective fashion.
Paul’s belief that the promise of cure of cancer utilizing combination chemotherapy and combined modality would be found within properly conducted cooperative clinical trials, especially those sponsored by the NCI and performed at multiple sites. This belief was not accepted by many who were in positions of authority. Some leaders at Yale and other institutions felt certain that radiation and surgery were the only means to address cancer and that chemotherapeutic agents were poisons whose toxicities were too great to allow them to be used on patients. Despite their fears, Paul persisted in his quest to utilize these agents and ultimately proved that his frightened detractors were quite wrong about their effectiveness.
Paul was able to stay on the cutting edge of oncology throughout his entire career. He had an unparalleled overview of what was happening in the field but was also a devoted physician to his patients, many of whom he continued to care for until the time of his death. Paul was stricken with head and neck cancer at an early age but managed to prevail for decades. This shaped his own career and life in many ways but he often used his own illness to better relate to and comfort those, who were attempting to balance hope and despair as they confronted their own struggles with cancer. He employed “the artful use of self” and his patients instantly recognized that their doctor had “been there” and knew what they were experiencing, and his advice was genuine and heartfelt. No matter what was occurring administratively, things stopped when patients telephoned him. Paul cared for patients until the very end of his life. Even when bedridden at home or hospitalized, he took their calls and advised them. The afternoon before his death with his secretary at his side, he went through a list of all patients for whom he was providing direct care and made arrangements for them to be assigned to a “perfect” colleague, after his passing.
Other biographers have noted Paul’s unique talent as a leader of influential governing bodies throughout the United States. He was a connector, a catalyst, and a facilitator who got the right groups and people assembled in order to advance the cancer care enterprise. Tom DeNucci described him as a chess master who could visualize potential challenges and solutions, many moves in advance.
In 1991, he was appointed as Chairman of the National Cancer Advisory Board by President George H.W. Bush and then appointed to the President’s Cancer Panel by President Bill Clinton. In 1998, President and Mrs. George Bush invited Paul to serve on the steering committee for the National Dialogue on Cancer and he was Chairman of its nominating committee. Senator Dianne Feinstein, in 1999, appointed Paul to the National Cancer Legislation Advisory Committee. [See photos with President George Bush in the Image Gallery]
In 1994, Paul chaired the National Cancer Advisory Board. Its recommendation to Congress included the following:
- A Cabinet-level official to coordinate work by the cancer institute and other government agencies, hospitals and private groups.
- Universal access to state-of-the-art treatment. Most managed care systems send patients to general practitioners instead of cancer centers, and keep patients away from top treatments because they will not cover drugs that are still in clinical trials.
- At least $60 million a year to move new discoveries into clinical trials, a bridge now almost totally neglected because money from drug companies and hospitals has disappeared, the panel said.
- An end to Federal price support of tobacco, which the institute says causes one-third of all cancer deaths. The panel condemned Federal tobacco subsidies, tax deductions for tobacco advertising and support for tobacco exports.
Paul was a believer. He had faith that chemotherapy, specifically combination chemotherapy would one day bring many cancers into remission, if not cure them as Vince DeVita had proven with Hodgkin’s lymphoma. He and DeVita were colleagues and good friends and as noted Paul served on several advisory boards and panels including those at Yale and the NCI, appointed by Vince. They collaborated on the idea of producing a MKSAP text for fellows and authored and co-edited books, guidelines and articles. Vince DeVita loved talking with Paul and looked forward to their Amtrak trips from New York City to Washington, D.C. during which a moment of silence never fell between them! Even when hospitalized, Paul insisted on running Yale Cancer Center Advisory Board meetings. There is a conference room and lecture named for Paul at Yale.
Paul’s accumulated wisdom was sought after by many societies and organizations. At the time of his death, Paul was a member of the Board of Overseers at the E. Bronson Ingram Cancer Center at Vanderbilt University and on the Board of Overseers at Tufts University School of Medicine. He was Chairman of the Advisory Committee for the Yale University Cancer Center and in a similar capacity, worked with the University of Wisconsin Cancer Center and the Columbia University Cancer Center. He was also a member of the Institute of Medicine and the National Academy of Sciences as well as a Master of the American College of Physicians. He was a member of the National Board of Trustees for the Leukemia and Lymphoma Society and an honorary life member of the Board of Directors of the American Cancer Society, having served as President of the Rhode Island Division from 1990–1992. He was president of the New England Cancer Society from 1994–1995 and served as president of the Rhode Island Cancer Council from 1999 until his death. He also chaired the Scientific Advisory Board of the T.J. Martel Foundation.
Paul received honorary degrees in the United States and abroad and was also awarded the Oscar B. Hunter Memorial Award in Therapeutics from the American Society of Clinical Pharmacology and Therapeutics and the St. George Medal for distinguished volunteer service from the American Cancer Society. He was President of the American Society of Clinical Oncology and was a member and leader of more than a dozen other professional societies. He served on nearly two dozen prominent committees and study sections at the NCI and was on the Editorial Boards of thirteen journals including the New England Journal of Medicine. Paul authored or edited more than 220 manuscripts and books on the pharmacology of anti-neoplastic agents and the management of cancer. He was very pleased with textbook “Medical Oncology” which he co-edited with Drs. Philip Schein and Saul Rosenberg.
Paul was an optimist according to his children. He always saw the bright side of things and never let anything get him down. When experiments didn’t go well in the laboratory or did not yield the anticipated results, he was never discouraged. Instead he learned from every failure and encouraged those in his laboratory to do the same. He provided words of reassurance and hope to those whom he mentored and by considering alternative explanations for experimental outcomes provided new ideas for his coworkers.
So too with clinical trials. If survival was not increased with a single agent or combination of chemotherapeutic agents, Paul would question why? Was it dose, formulation, sequence of medication? Could it be that the therapy was instituted too early or too late in the course of the illness? Could it have been that the tumor target was wrong and another cellular substitute would have responded better?
Paul’s mentorship skills were legendary. Roy Herbst, Chief of Medical Oncology at The Yale Cancer Center—whose good fortune it was to meet Paul, on his first day as an undergraduate student at Yale College where he was randomly assigned as a roommate with Peter Calabresi, Paul’s son—said, “I would not be an oncologist if it weren’t for Paul Calabresi. He took me under his wing and guided me. It was truly highly personalized mentoring. He gave me a sense of direction, and showed me the importance and value of developing close relationships with colleagues.”
Ed Chu knew Paul through his parents who worked with Paul at Yale and then brought them to Brown in 1968. His father, Shi-Hsi Chu, worked in Paul’s laboratory at Roger Williams Medical Center and his mother, Ming-Yu Chu, in the pharmacology department at Brown. They were part of a highly skilled group of scientists Paul had assembled to develop chemotherapeutic drugs which would move quickly to be tested as part of clinical trials. One such medication which was originally intended to treat cancer was repurposed by Paul and others to treat viral infections especially herpes virus type 1. It was used in Rhode Island to save the life of an infant with herpes encephalitis. The drug 5-iodo-2 deoxy uridine (IDU) was injected into the brain of the infant and saved its life.
Dr. Calabresi was also important in Ed Chu’s career. Paul emphasized the importance of having the clinical world of oncology partner with pharmacology. He was a true pioneer in what we now call translational research. As with Roy Herbst, Paul was a role model for the importance of warm interactions with colleagues and stressed how working well with others could clearly benefit drug development and ultimately patients in need.
Dr. Bruce Chabner met Paul at Yale in Dr. Joseph Bertino’s laboratory. Biochemical pharmacology served as a common bond for Paul and Bruce and friendship and collaborations soon developed. Proudly for both individuals; they co-authored the Goodman and Gilman “Pharmacologic Basis of Therapeutics” chapter on chemotherapy of neoplastic diseases. Paul was regarded by Bruce Chabner and many others as an ideal mentor. A relationship with Paul was never trivial. Perhaps more than any other physician/scientist, he became the inspiration, guide, and counselor for countless friends and oncologists. Bruce Chabner also stated, “Paul was an incredibly savvy guy.” He could visualize the totality of all arguments about large decisions being made and was an ambassador of good will for the NCI as it struggled with the best way to conduct cooperative clinical trials and award grants and contracts. Chabner and Calabresi collaborated in the laboratory and as editors and authors in major texts and journals. Bruce believed that 3 contributions stood out and are legacies of Paul:
- Paul was most knowledgeable about purine pathways and medications which could interfere with them to treat both dermatologic conditions and malignancies.
- His insights into the possibilities for antimetabolite medications was creative and unmatched by contemporaries.
- His leadership abilities were outstanding. His presence, forthright nature, articulateness and diplomatic skills were able to propel ideas and policies at a national and international level but were also obvious locally as he took the fledgling Brown Medical School to a higher level of scientific and clinical vigor and accomplishment.
Later in Paul’s life, and once again being ahead of the curve, Paul developed an interest in geriatric oncology and served as the founding president of the International Society of Geriatric Oncology in 2000. He promoted geriatric oncology and as a scholar whose mastery included medicine, epidemiology and understanding of the human condition, he studied and publicized the effects of cancer on the elderly.
Paul was a world traveler and avid sailor. Bruce Chabner in a 2003 tribute described Paul “…as the master of the Calabresi ship as it steered its way through Yale, Brown and Washington. Paul led the way for the continuous stream of talented Calabresi’s, a remarkable family that has become renowned in law and medicine.” Paul’s brother, Guido, was the youngest full professor at the Yale Law School and then became its Dean. Paul’s children have gone on to make significant contributions in the world of law and medicine: Steven Calabresi, Clayton J. and Henry R. Barber Professor Northwestern Pritzker School of Law, Janice Calabresi Maggs, Attorney at Law, formerly Special Counsel to the Assistant Attorney General for the Civil Division of the U.S. Department of Justice, and Peter A. Calabresi, MD, Professor of Neurology, Neuroscience, and Ophthalmology, Director, Division of Neuroimmunology and Neurological Infections, Co-Director, Multiple Sclerosis Precision Medicine Center of Excellence, Johns Hopkins University School of Medicine.
Dr. Paul Calabresi died on October 25, 2003 in Providence, Rhode Island. Ironically, he succumbed to complications of his recurrent cancer, the disease which he had been studying and helping to conquer during his entire professional career. He faced death with the courage and grace he demonstrated throughout his life.
After Paul’s death, the International Society of Geriatric Oncology instituted a Paul Calabresi Memorial Lecture. Brown University established the Paul Calabresi Lecture and Professorship, and the National Cancer Institute established the Paul Calabresi Award (K-12), a multi- and trans-disciplinary institutional training award supporting research career development of clinicians and Ph.D. basic scientists.
Paul Calabresi was a guide and counselor to many. All of us will miss him. In a memorial article, Dr. Gregory Curt characterized Paul well “…Paul was a voice of reason and leadership and he earned real respect and friendship in each distinguished circle.”
I could think of no one better to speak with about a tribute to Paul Calabresi in the Cancer History Project than my colleague Fred Schiffman at Brown University as he knew Dr. Calabresi personally during decades of working together.
I was delighted that Fred was willing to help (working with contributing colleagues) to recount some history about the life and contributions of Paul Calabresi to the world of oncology and cancer medicine.
Dr. Calabresi spent much of his career in Rhode Island including as Chair of Medicine at Brown for two decades after moving from Yale. His national impact as an early President of ASCO, as someone who helped establish the field of oncology and as founding President to the Society of Geriatric Oncology are well known. Among awards named after him, the NIH Paul Calabresi K12 award, highlights his impact and lasting legacy on training of oncology investigators.
Dr. Schiffman previously paid tribute to Dr. Calabresi in 2006 after his passing in 2003. It was great to learn about the connections and the impact of Dr. Calabresi’s family and the connections with his contemporary colleagues who knew first hand about his contributions and legacy beyond what is in the public domain.
In the course of getting together the manuscript, I realized that my close colleague Dr. Wolfgang Oster had spoken about Dr. Calabresi both from the point of view of a clinical oncologist who worked with him and that later he had interacted with him in his advisory roles with industry.
As we have been building a world-class Cancer Center at Brown University, it is important for us and the world to learn some history about Dr. Calabresi, his world-wide impact in oncology and his impact while at Brown University. In fact Dr. Calabresi was the Director of an NCI-supported Cancer Center at Brown University in the 1980’s.