Wayne Rundles, MD, PhD
In May 2023 surrounded by members of the Rundles family, I vocalized a long-time desire to understand the professional accomplishments of my father, R. Wayne Rundles, MD, PhD (1911-1991), founding chairman of the Division of Hematology at Duke University. His contributions to hematology are many, with a legacy that continues today through the generations of doctors he trained and the lives he touched.
One of the significant aspects of my father’s career was his decades-long collaboration and friendship with Nobel laureates Gertrude “Trudy” Elion, PhD, and George Hitchings, PhD. He would later describe this work as symbiotic and complementary. Drs. Elion and Hitchings were chemists at Burroughs Wellcome, and in those days, very few doctors had relationships with pharmaceutical companies. Yet his willingness to explore collaborations with pharma led to Duke being the clinical arm of Drs. Elion and Hitchings’ pioneering research. So interconnected was their work that many believed it was an oversight when my father was not awarded the Nobel alongside Drs. Elion and Hitchings.
Treating Cancer — and Gout
Dr. Rundles at the microscope.
Drs. Elion and Hitchings were responsible for synthesizing 6-mercaptopurine (6-MP) in the early 1950s and quickly determined that it had an antitumor response. Aware of their work, my father traveled to meet Drs. Elion and Hitchings at the Burroughs Wellcome headquarters in Tuckahoe, New York. The trio hit it off, and until 1962, they would investigate ways to make 6-MP more effective — eventually coupling it with allopurinol, which can alter 6-MP metabolism to maximize the active anticancer metabolite while reducing the production of a hepatotoxic metabolite, thus widening the therapeutic window.
The combination of 6-MP and allopurinol was first used in a patient with chronic myeloid leukemia (CML) who also happened to have severe gout. The patient often remarked how his gout was improving in a way it never had, so my father, John Laszlo, MD, and their team brought this finding to Drs. Hitchings and Elion. We now know that by inhibiting xanthine oxidase, we can lower blood levels of uric acid, which is deposited as crystals in the joints of patients with gout. Allopurinol would quickly go on to become the standard of care for treating gout.1,2 If a book were to be written about my father, one colleague suggested it could be titled “The Man who Cured Gout.”
Studying Individuals and Sharing the Findings
Dr. Rundles at work in his home
office.
While his clinical research in allopurinol was indeed significant, it could be considered secondary to the essence of my father’s work as one of the original chemotherapists. His early findings exploring ethyl carbamate against myeloma were published in 1949.3 Much progress sprang from the creation of the Southeastern Cancer Chemotherapy Cooperative Study Group (SCCCSG), which he organized and led from 1956 to 1966. The comparative studies run through SCCCSG — in which different hospitals would follow the same protocols as they investigated the application of new drugs and approaches — would become a model for modern clinical trial networks.
Eventually, he broke ties with SCCCSG as they began to launch larger clinical trials. My father believed that incremental progress could be seen in a very small number of patients; he thought it was far better to study one patient thoroughly versus 400 poorly. The care my father took to really talk with his patients — to understand them, to ask questions about how they felt physically after receiving chemotherapy — would yield answers that would help advance the field of medicine.
Early art education between a
father and daughter.
My father’s fellows remember him working for years, from about 1967 until 1972, on the first edition of the “big book,” Hematology (now William’s Hematology). This monumental collaboration, which also included William Williams, MD, Ernest Beutler, MD, and Allan Erslev, MD, has been reprinted many times over and is the landmark textbook on how blood diseases are understood, a sentiment that remains today with its 10th edition.
Outside of clinical research, my father’s leadership roles included the American Society of Hematology, where he served as secretary from 1962 to 1965 and president in 1967. His longtime involvement with the American Cancer Society (ACS) led to an appointment as president in 1976. He relished traveling the world as part of these roles, and he would continue volunteering for the North Carolina chapter of the ACS until his dying day.
A Glimpse into His Personal Side
My father was a Renaissance man with a quick wit and a twinkle in his eye. He was an early adopter of the latest camera equipment from Japan; a collector of maps and gemstones; a lover of Japanese art and irises; and an avid reader and thinker. He was the proud owner of a Walkman months before they hit the U.S. market. One friend noted that the first thing he would do upon arrival in a new city was identify a high-end men’s shoe store, not necessarily with the intent to buy but to peruse the latest footwear trends.
He was known for saying, “Don’t just do something, stand there.” No one quite understood what this meant, but I suspect it had to do with his belief that a person needed to fully understand a situation before acting. Everyone remembers his mustache and how it would twitch as his dry humor emerged.
Dr. Rundles (left), daughter,
Martha, and wife, Margo, about
to embark on a cruise around the
British Isles in 1985.
He was notoriously late — forever rounding on his patients — and a perfectionist, known for making extensive edits to patient notes and manuscripts using his red and blue felt pens. He would edit and then edit some more. A colleague described him as having the ability to think “very small and very big at the same time.” Always teaching and mentoring fellows, my father was constantly at the microscope drawing attention to subtle changes in lymphocytes in patients with chronic lymphocytic leukemia and myeloma.
Like the discovery of allopurinol as a treatment for gout, my father held the hand of serendipity and had some lucky breaks along the way. In his own words, he played the hand he was dealt extremely well. Was it luck that he befriended pre-med students at DePaul University and that a series of events led him to Duke via Cornell? His chance meeting of my mother, as she was on the verge of leaving Durham, was another lucky break and gave my father many decades of happiness. Their 30-year age difference made perfect sense to anyone who knew them. They enjoyed entertaining and had many close friends. I remember them enjoying a nightcap in bed every night as they shared high points from their days.
My father’s dear friend Wendell Rosse, MD, summed up his many achievements with the following: “A life well lived is one that leaves the world a better place for its having been. Wayne’s life, by that definition, was very well lived indeed. His contributions, direct and indirect, have been enormous, and he has been honored greatly for them. But perhaps his greatest contribution is the influence he had over the young people he trained and those they have trained. For this he is honored by the continuous contributions these students and the students of those students have made.”
References
- Rundles RW. The development of allopurinol. Arch Intern Med. 1985;145(8): 1492-1503.
- American Society of Hematology. ASH oral history: Wayne Rundles. 2008. Accessed April 24, 2024. https://www.hematology.org/about/history/legends /wayne-rundles-bio/wayne-rundles-qa.
- Loge JP, Rundles RW. Urethane (ethyl carbamate) therapy in multiple myeloma. Blood. 1949;4(3): 201-216.
