Donald P. Pinkel: In Memoriam (1926–2022)

Donald Paul Pinkel, MD, died on March 9, 2022 at 95. A pioneer in pediatric oncology, Pinkel staked his career on the belief that children with acute lymphoblastic leukemia (ALL) could be saved during an era when few physicians were bold enough to mention the word “cure.” Through a series of landmark studies, Pinkel developed a cure for ALL—the most common childhood cancer once considered universally fatal—and earned a place in medical history. He was an innovative researcher, a compassionate physician, and a courageous leader who provided the foundation for modern childhood cancer treatment.

Born in Buffalo, NY, Pinkel joined the U.S. Navy during World War II at age 17. He was assigned to medical officer training at Cornell University (Ithaca, NY). After developing an interest in biology, he entered the medical program at the University of Buffalo (Buffalo, NY). He was drawn to pediatrics, most notably pediatric oncology. At the time, childhood cancer was almost always fatal. During rounds, if someone mentioned a child had leukemia, the group would not stop at the patient's room. Pinkel said that he hated seeing children and their families dismissed and shunned. After rounds concluded, he would return to talk with the family and child.

As a survivor of polio and an empathetic pediatrician, he understood the crushing despair of disease and the potential of medical research. He worked with renowned Boston researcher Sidney Farber, MD, and later became the chief of pediatrics at Roswell Park Cancer Institute (New York, NY). With a burgeoning career ahead of him, Pinkel was strongly considering an offer from the University of Colorado Medical Center (Aurora, CO). Then a call came from Memphis.

Danny Thomas, a well-known comedic actor, had amassed funds to build a children's hospital, and the institution's search committee wanted to know if Pinkel would serve as its first medical director. St. Jude offered Pinkel the opportunity to build a program that moved beyond prolonging life in comfort—the standard palliative care—for children with cancer. Pinkel was intrigued. He believed he could use the knowledge he had gained in the lab to develop a cure for ALL.

“The disease was neglected, and no one was doing much in the way of research or in actual care because they were so frustrated. I felt an obligation to fill the vacuum,” he recounted in the Cancer Letter's Cancer History Project (1). Standard treatment for leukemia was to use one drug at a time, reserving other drugs for recurrent disease, or to allow patients to “die in peace.” Although the child's cancer would respond initially to the single-agent approach, Pinkel noted that the disease almost always roared back with devastating results and the patient would eventually die from the disease. What had not been closely examined was combination treatment with multiple drugs—an approach many in the field felt was cruel.

Pinkel accepted the job and became the first employee of St. Jude. He arrived at the hospital in 1961 while it was still under construction—a year before its first patient would be admitted. His office was equipped with a table and chair, and two wires from outside utility poles—one for the telephone and the other for light and heat. Immediately, he began recruiting researchers and clinicians from around the country to share his vision and applied for grants from the National Cancer Institute (Rockville, MD).

Many in the medical and scientific community mocked him for believing childhood leukemia could be cured. Undeterred, he built a robust collaborative culture where researchers and clinicians worked together, establishing the bench-to-bedside approach to clinical research now seen as a gold standard. “I recall Dr. Pinkel's response to a faculty member who was upset about having to walk through the patient waiting rooms on his way to his laboratory every morning,” said Robert Webster, PhD, emeritus faculty at St. Jude. “He asked Don if he could arrange for a separate entrance for the scientist. Don's immediate response was, ‘I want you as a scientist to see the children every day to realize the importance of our mission here at St. Jude.’”

The early years were filled with heartache for both parents and staff. More children were lost to cancer than were saved. But Pinkel and his team persevered, developing the Total Therapy approach using combination treatment for ALL. “My hypothesis was that there were some leukemia cells that were sensitive to one drug and other cells that were sensitive to another. But if we used all these drugs at once and hit them along different pathways, we could permanently inhibit the development of resistant cells,” he later told a reporter from Smithsonian magazine (2).

Pinkel devised a series of Total Therapy studies, with each successive trial building on the knowledge of its predecessors. The first four studies showed that combination chemotherapy is superior to the sequential administration of single agents in overcoming drug resistance, and full-dosage continuation chemotherapy with mercaptopurine, methotrexate, vincristine, and cyclophosphamide is superior to the same drugs given in half-dosage.

James Eversull, who was treated as a child for ALL on Total Therapy III, remembers Pinkel as exceedingly kind, but also very serious about his work. “He gave my parents hope, and the Total Therapy approach ultimately gave me a cure. He saved my life, and for that, I'll always be grateful.”

By the late 1960s, when relapses did occur in children, more than 60% occurred in the central nervous system (CNS). “Pinkel recognized the need to treat the CNS separately because most antileukemia drugs could not readily cross the blood–brain barrier,” said Stephen E. Sallan, MD, chief of staff emeritus of Dana-Farber Cancer Institute. “This addition of prophylactic treatment of the CNS markedly increased the incidence of cures in childhood ALL.” Pinkel then divided the regimen into several components, which included remission induction, consolidation, continuation, and CNS-directed treatment. These components remain the backbone of ALL therapy today and also became the thought-starter for adult oncologists tackling cancers such as multiple myeloma.

In Total Therapy V, a study conducted from 1967 to 1968, Pinkel increased the intensity of both systemic chemotherapy and CNS-directed treatment, boosting the survival rate of ALL from 4% to 50%, marking the first significant cure rate for generalized cancer (3). Pinkel and his team continued the Total Therapy trials, refining the therapy with the goal of increasing survival rate while reducing long-term toxicity. He was the first investigator brave enough to eliminate therapy after 30 months of continuous complete remission, reporting his success in 1974 (4). Today at St. Jude, Total Therapy is in its 17th iteration, and ALL has a 94% survival rate. The therapy Pinkel helped develop is now being used to treat children and adults worldwide.

When Thomas founded St. Jude on the principle that no child would be turned away based on race, religion, or ability to pay, it became a deciding factor for Pinkel in taking the job at St. Jude. “I felt that this was a time of change and resolve…and that it would be an opportunity to be in there at the historic point and have a hospital that would be totally integrated,” Pinkel said. Aligned with Thomas’ vision, Pinkel developed an inclusive culture. St. Jude offered opportunities to patients and employees alike, regardless of race—whether it was lifesaving treatment or the ability to pursue careers in medicine or science. It was a bold commitment, but Pinkel led with unwavering determination. Under his guidance, St. Jude became the first integrated children's hospital in the South. Pinkel negotiated with surrounding hotels to provide housing for patient families, regardless of color.

“What made me want to come to St. Jude was that we had the opportunity to take science and to meld it with great humanity,” Pinkel said. In addition to his work in childhood cancer, Pinkel led St. Jude to collaborate on the MAP-South–St. Jude nutrition and health program. The initiative, which identified and sought to treat malnutrition in local infants and children, became the basis for the federally funded Special Supplemental Nutrition Program for Women, Infants and Children, or WIC.

Many also remember Pinkel as an invaluable mentor. “Don was the CEO when I joined St. Jude as a student technician in 1972,” said William Evans, PharmD, who later became director and CEO of St. Jude from 2004 to 2014. “He was ‘old school’ in many ways—we had grand rounds on Saturday mornings—yet he welcomed ideas from anyone who had done their homework, even students like me. He set the culture of collaboration and innovation that remains the foundation of St. Jude to this day.”

Pinkel left St. Jude in 1973 to become chief of pediatrics in Milwaukee, WI, later establishing the Midwest Cancer Centre at Milwaukee Children's Hospital. He felt that 10 years at the helm was long enough for a place that wanted to remain at the cutting edge. He continued to build pediatric practices, serving as a director at City of Hope Hospital in Duarte, CA, and St. Christopher's Hospital in Philadelphia, PA. In 1985, he joined M.D. Anderson Cancer Center in Houston, where he developed clinical trials using biological covariates including genotype and immune phenotype to direct therapy (5). The aim was to provide what we term today as precision medicine. Another goal was to eliminate the use of prophylactic CNS radiation to improve quality of life after treatment, a goal achieved a decade later at St. Jude. He retired in 1994 but continued to teach in Houston. In 2002, he moved to San Luis Obispo, CA, and became an adjunct professor at California Polytechnic State University. There, he taught courses in medical virology, medical mycology, and emerging infections until he was 89.

For his incredible achievements, he was honored with the Albert Lasker Medical Research Award, the Charles F. Kettering Prize for Cancer Research, the Pollin Prize for Pediatric Research, and many other international awards. In 2017, St. Jude dedicated a research facility in his name, honoring his commitment to translational medicine. The Donald P. Pinkel, MD, Research Tower is home to international researchers and cutting-edge scientific programs.

Pinkel married Marita Donovan, a Buffalo native, in 1949 and had nine children. In 1982, he married Cathryn Howarth, MD, and had one son. In addition to one surviving sister and nine surviving children, he leaves sixteen grandchildren, five great-grandchildren, many nieces and nephews, and his wife, Cathryn.

A favorite quote of Danny Thomas was “To cure one child in Memphis is to cure a thousand worldwide.” Pinkel's monumental legacy lives on through the countless lives saved through his work and the research questions he inspired others to pursue. His tenacity as a researcher, compassion as a physician, and drive to solve some of medicine's most difficult questions have made him an inspiration to thousands around the globe.