The world lost one of the true pioneers of cancer treatment last week with the death of Donald Pinkel, MD, at age 95.
Dr. Pinkel — the founding director of Roswell Park Comprehensive Cancer Center’s Pediatric Oncology program, who was recruited in 1961 to become the first director of St. Jude Children’s Research Hospital in Memphis, Tennessee — developed the combination treatment regimen that changed the most common cancer in children, acute lymphocytic leukemia, from a highly fatal disease to a cancer that almost every affected child now survives.
We reproduce here an article that appeared in Roswell Park’s “RPCI Alumni News” magazine in late 2010, based on an interview with Dr. Pinkel, who by then was retired and living with his family in California.
We proudly republish this article to celebrate Dr. Pinkel’s incredible legacy — for the benefit of those who knew him well as well as those not aware of his outsized influence on the care of kids with cancer.
“Dr. Pinkel was a luminary whose brilliance, grit and determination gave the world what remains the most dramatic, most impactful, most enduring breakthrough in cancer treatment that we are ever likely to witness. He achieved things that had been written off as impossible, saving hundreds of thousands of lives by refusing to give up when everyone else would have. We are extraordinarily proud of his legacy and ever-mindful of the example he set for us,” says Barbara Bambach, MD, one of Dr. Pinkel’s successors as a hematologist/oncologist with the Roswell Park Oishei Children’s Cancer and Blood Disorders Program.
“Never run away from a fight. The farther you run, the more difficult it will be to fight back.” That advice—delivered some 70 years ago by a high school coach—has come back to Donald Pinkel at pivotal points in his life. At times he faced heavy odds, but he always persevered and moved ahead, building and leading Roswell Park’s first Pediatrics Department, overseeing the development of St. Jude Children’s Research Hospital as its first director, and playing a key role in dramatically raising the survivorship rates for childhood cancer.
Even during his formative years in Kenmore, New York, his childhood experiences hinted at the lifework ahead. At the age of five he learned about the human circulatory system through diagrams drawn by his older sister, Ann Marie, a nursing student. And he was always around babies: “When my mother stopped having babies, my older sister started having babies,” he recalls, “so I used to do a lot of babysitting.”
Later he won a full scholarship to Canisius High School, then located on Washington Street in Buffalo, and the route he traveled to get there took him past the New York State Institute for the Study of Malignant Diseases, later to become Roswell Park.
At 16, he knew he wanted to pursue a career in medicine. Though he loved studying the classics—Greek, Latin, and the philosophy, culture, and history of ancient Greece and Rome—he thought he should focus on science instead. “No, no,” the principal told him. “You must read the humanities; you must know why you are going into medicine first. You will get plenty of science later on.”
During his senior year, with World War II in full swing, he enlisted in the Navy. The day after graduation, he was ordered to report to Cornell University for active duty, to begin an intensive pre-med program that would prepare him to become a medical officer. Two years later, after the war had ended, he entered the reserves and returned to Buffalo, where he could “live at home very cheaply and get a part-time job.” He finished his undergraduate work at Canisius College and entered medical school at the University of Buffalo.
It was during medical school at UB (1947-51) that he first became interested in leukemia, while working with Professor David Miller, MD, at E. J. Meyer Memorial Hospital, now the Erie County Medical Center. “I took hematology with him and did some research in his lab,” says Dr. Pinkel. “He became my model. He was a wonderful teacher, a good scientist, but also a wonderful bedside physician. I loved making rounds with him.”
The young man’s interest in cancer intensified during a rotation at Roswell Park and later when he served as Chief Resident at Children’s Hospital of Buffalo. “They had a fine hematologist but no oncologists at Children’s, so I set up a cancer service and registry and a Tumor Board, with support from the local chapter of the Cancer Society,” he recalls.
But when he told UB Professor of Pediatrics Mitchell Rubin, MD, that he hoped to focus on pediatric cancer research, Dr. Rubin cautioned him that he might be “throwing away his career”—a reflection of the prevailing notion that pediatric cancers were “hopeless.” Such pessimism was understandable, especially when it came to pediatric leukemia. Acute lymphoblastic leukemia (ALL) killed more American children past infancy than any other disease. An ALL diagnosis was virtually a death sentence, with a grim survival rate of just 4%. Though clinical research was the only hope, many physicians declared it unethical to involve children in clinical studies, asserting that it would only prolong their suffering.
Despite his misgivings, Dr. Rubin sent the young physician to talk with George Moore, MD, then Director of Roswell Park, who was laying plans to add a Pediatric Department at the Institute. Recalls Dr. Pinkel, “He was very encouraging.”
Dr. Pinkel remained passionate about his chosen field, but his life took an unexpected detour. He had graduated from medical school with a commission as an Army Medical Officer in UB’s 338th General Hospital Reserve Unit. Three years later, in 1954—while preparing to move his young family to New York City so he could begin a fellowship in pediatric oncology—he received orders to active duty and was assigned to the U.S. Army Hospital at Fort Devens, Massachusetts. There he cared for the families of area servicemen as Chief of Pediatrics and the sole pediatrician.
When an epidemic of poliomyelitis broke out, life came to a standstill. “I thought I was immune to it,” he says. “We had big epidemics in Buffalo in the 1950s, and I took care of hundreds of children with polio. But at Fort Devens I happened to be over-tired; I was staying up a lot with sick children, and I was the only pediatrician. I came down with it worse than any of my patients.
“While hospitalized at Fort Devens, my respiratory function went down to a small fraction. I remember going to sleep one night and thinking, Well, this is it. I’m not going to wake up.”
He did wake up, but to a life vastly different from the one he had known before. Now he was paralyzed and totally dependent on others to feed and bathe him. Transferred to Murphy Army Hospital in Waltham, “I quickly became severely depressed, because I couldn’t do anything for myself,” he recalls. “I began to realize that much of my disability would be permanent. I thought, What am I going to do? But I was married and had three children, and I wanted to survive for them.”
One night the medical officer on duty came to his bedside and told him that a baby was very sick and no pediatrician was available. Would Dr. Pinkel examine her? The officer wheeled him to the nursery on a gurney, “and there was the baby, with bad diarrhea—very dehydrated. I was able to lean over and examine her and start an IV and write the orders. And I thought, That’s the most wonderful thing that could happen to me.”
In the weeks afterward, physical therapy helped him progress from gurney to wheelchair, from wheelchair to leg braces and crutches. In 1955 the Army declared him permanently unfit for duty. He was retired from service and transferred to a VA hospital in West Roxbury, Massachusetts, to continue his recovery and rehabilitation.
West Roxbury is less than 10 miles from Boston, where Sidney Farber, MD, a fellow Buffalonian and UB Medical School alumnus, had established the Children’s Cancer Research Foundation, later to become Dana-Farber Cancer Institute. A series of introductions led Dr. Pinkel to Dr. Farber. “I’ll take you on as a half-time fellow while you continue your therapy,” Dr. Farber told him, “but you must promise that your work will not interfere with your rehabilitation.”
Under Dr. Farber’s mentorship, Dr. Pinkel began studies of experimental chemotherapy of children’s cancers, a field viewed by many as “quackery.” He was assigned to study actinomycin D, “a natural antibiotic identified by Dr. Selman Waksman that had shown anti-cancer effects in mice with experimental leukemia and other cancers,” explains Dr. Pinkel. “We showed that it destroyed metastatic Wilms’ tumor and childhood rhabdomyosarcoma—cancers that, until then, were almost universally fatal. Actinomycin D was the first antibiotic to demonstrate anti-cancer activity in humans and the first drug with destructive effects on these two childhood cancers. It was also the first drug to be effective in reducing risks of recurrence of these cancers when combined with surgery and/or radiation therapy and in reducing non-operable tumors to allow their complete and less-radical removal.”
In 1956, while working with Dr. Farber, Dr. Pinkel learned that Roswell Park was recruiting for its new pediatrics service. He took the train to Buffalo, met again with Dr. Moore at Roswell Park and with Dr. Rubin at Children’s Hospital, and came away with an offer of a joint appointment at the two institutions. He was 29 years old and ready to get going.
“We worked out that all the residents at Children’s would rotate to Roswell Park in Pediatrics,” he says. “That was unique; no other hospital in town rotated to Roswell regularly.” He also organized the pediatric clinic and ward—complete with a playroom—and worked with other departments to develop pediatric nursing, laboratory, pathology, and radiology. With the Institute’s research scientists, he also developed a pediatric cancer research program, focusing heavily on possible viral causes of leukemia.
At the time, the Institute had only one part-time physical therapist, and Dr. Moore granted Dr. Pinkel’s wish for a “full-scale, active rehab unit.” Dr. Pinkel remembers hiring a speech therapist “who worked with adults who had had laryngeal cancer. He was a ventriloquist! He’d throw his voice all over the place.”
And Dr. Pinkel collaborated with Walter Murphy, MD, then Director of Radiation Therapy, ”an excellent radiotherapist—a pioneer. There were certain tumors like Ewing’s sarcoma where the book said to treat them with radiation therapy. I’d sit down with him and say, ‘Walt, I think I can shrink that down for you with chemotherapy before radiation.’ With the consent of our patients’ parents, we used chemotherapy and radiation together to achieve better survival with less radiation exposure.”
Roswell Park also nurtured Dr. Pinkel’s fortuitous collaboration with James Holland, MD, then Chair of Medicine at Roswell Park. “Jim was in charge of adult leukemia. When I first got there, we teamed up with Tom Frei and Jay Freireich at the National Cancer Institute (NCI),” says Dr. Pinkel. “We formed a cooperative group, which became the Cancer and Leukemia Group B (CALGB). We began to organize studies on treatment for leukemia and met every six or eight weeks at the NCI. We developed research protocols so we could treat our patients and learn as we went along whether we were doing the right thing.
“I loved working at Roswell Park. It was very significant to me, because it was my first job, and I had been concerned whether anyone would hire me with my disabilities. All of a sudden I was going on all my cylinders again.
“I was very lucky; Roswell Park was one of my good fortunes. That position came at just the right time and right place, and offered me opportunities I might not have had otherwise. I really love that institution. One of its great features was its acceptance and optimal care of all people of the state without regard to their means.
“I thought I’d be there the rest of my life, but the last winter I was there , I had bad pneumonia, and with the snow and ice, I had problems ambulating. I had a very bad winter.” At last his thoracic physician advised him to move to a milder climate.
Serendipitously, Dr. Jim Sweeney, a former colleague at Children’s Hospital who had moved on to the University of Tennessee Medical School, stopped by Roswell Park one day and told Dr. Pinkel about a new hospital that entertainer Danny Thomas planned to build in Memphis. “Would you be interested?” Dr. Sweeney asked. “They need someone in the field of leukemia and pediatrics. It’s just up your alley.”
Dr. Pinkel balked at the prospect. Schools, parks, and even hospitals were segregated in Memphis, and “I had vowed I’d never go South, because there was so much prejudice down there.” Besides, he was already weighing an offer of a “sweetheart job” at the University of Colorado Medical School. He went to Memphis for the interview but came away burdened with the same heavy doubts.
But the more he thought about it, the more he was attracted by the twin challenges of creating a university-associated pediatric research hospital from scratch and confronting the racism he abhorred. He had to confirm that the leadership of the fledgling St. Jude Children’s Research Hospital shared his vision, and that the hospital would “accept all children, including black children, and that there would be integration on all levels—staff, nurses, everything.”
He arranged to meet with Edward Barry, Chairman of the Board of St. Jude, and Michael Tamer, Executive Director of the American Lebanese Syrian Associated Charities (ALSAC—the fundraising arm of St. Jude), at the Conrad Hilton Hotel in Chicago. On the Fourth of July, 1961, the three men sat in a tiny hotel room and talked about the possibilities for St. Jude.
“I told them where I saw my vision: a hospital with first-class research, taking all children and starting off with children who had leukemia or other forms of cancer, and over time going on to other incurable diseases, like muscular dystrophy, to see what we could do using both laboratory science and clinical research and excellent patient care. And also to serve as a model and training ground for other research pediatricians and scientists.”
Dr. Pinkel and Mr. Barry quickly found common philosophical ground, recalls Dr. Pinkel. “And Mr. Tamer was a big, warm-hearted Lebanese man, a very nice person. He said, ‘I leave it to you and Ed Barry to decide all these things, but I like what you’re saying, and I’ll support you.’ He felt very strongly about civil rights, too. At the end of the day, we all shook hands and said, ‘OK.’”
There was much to do to get the new hospital off the ground. “They were running out of money, and I had to get money for the patient wing,” recalls Dr. Pinkel, who was then just 34 years old. And recruiting faculty and staff “was a real challenge. Nobody wanted to move there, because the Civil Rights struggles were going on.”
But there were also benefits in starting a brand-new institution: “The people who are willing to come are more dedicated, more innovative, more adventurous. You get people who are asking questions, not afraid to do something different. They aren’t there for the prestige. They aren’t there for the money, because we didn’t have much money; to a large extent, we needed grants to accomplish our mission.”
In those tenuous first years, he often drew support and encouragement from Danny Thomas. “He was very bright, and when there were problems, he’d come to see me and we’d talk them over, and he’d back me up all the way. But it was Mr. Barry, Chairman of the Board, who lived in Memphis, who was our daily supporter and guarantor.”
The NCI provided significant financial support as well, to help cover construction costs and to establish training programs for students from the University of Tennessee. “I got some of the best students,” says Dr. Pinkel.
Four years later, St. Jude was receiving more pediatric leukemia patient referrals than any other institution in the world—and every child was treated free of charge, as Danny Thomas intended. After spending several days visiting St. Jude, Kenneth Endicott, MD, then Director of the NCI, told Dr. Pinkel, “I want to do everything possible to make your operation one of the best in the world.”
Ultimately, the goal of becoming “one of the best” was driven principally by the institution itself, and Dr. Pinkel set the tone. “I was at St. Jude in 1972 as a student, and the atmosphere of the institution was unbelievable,” says William Evans, PharmD, current Director of St. Jude. “Dr. Pinkel encouraged people to bring their ideas forward. They needed to be thought through, well thought out, but he didn’t think ideas came only from physicians or PhD scientists. If a student had a good idea—or any member of the team, be it a nurse or pharmacist or physicians—he encouraged it. He brought people together, encouraged them to speak up. And the work ethic! He was a tireless worker—there all the time, Grand Rounds on Saturday morning.
“That’s part of our DNA now. In a way, he laid the foundation for the culture of St. Jude—a culture of collaboration, of innovation and teamwork.”
When the hospital opened in March 1962, Dr. Pinkel focused even more keenly on new treatments for ALL. “In 1962, the most we could hope for was to extend life,” he recalls. While remission was possible and survival prolonged when children were given anti-leukemia drugs in succession, the reprieves weren’t durable. “When the children were in remission, they could be pretty healthy,” says Dr. Pinkel. “They could go to school, play sports and so forth, but on average, youngsters with ALL would last about a year and a half when we used one drug at a time.
“I began thinking, We have to look at this more aggressively. So I got the idea of what I called Total Therapy—use everything. It was a radical notion. I wrote up the protocol, based on experimental and laboratory work, achieving quick remission using prednisone, vincristine, and later asparaginase also, then going on to intensification with high doses of methotrexate, mercaptopurine, and cyclophosphamide to minimize the residual leukemia. Then we continued combination drug therapy with these agents for two to three years to eliminate the rest of the leukemia cells.”
But there was another hurdle to surmount: because the drugs were poorly diffused in the cerebrospinal fluid, almost half of treated pediatric ALL patients developed disease in the central nervous system, even when they remained in complete remission in their marrow and blood. So Dr. Pinkel’s team introduced a treatment phase in which drugs were injected into the spinal fluid early in remission, and patients also received moderate-dose cranial radiation. “We did pilot studies and modified them as we learned,” says Dr. Pinkel. “The cranial radiation was later abandoned when it was found that periodic treatment of the spinal fluid with a three-drug combination was sufficient, and radiation was too risky.
“We had some wonderful staff—very patient, tolerant, skilled bedside doctors, nurses, technologists, research scientists and Catholic Sisters, all hard workers who shepherded these youngsters through and engaged in excellent basic biological and clinical research.
“Those early years were especially difficult. People were saying we were nuts trying to cure ALL. I received unpleasant letters from some of my colleagues who thought it was foolhardy and deceptive. There were days when I wondered if we were doing right, especially as previously rare infectious diseases like pneumocystis pneumonia became common because of the intense immunosuppressive effects of the drugs. But I remembered when parents would come to me and say, ‘We know our child is going to die, but if you can learn something that might help other children, please do it.’ And our supporters, ALSAC and the NCI, firmly supported our work.”
Success built on success until, by 1970, data from the first three clinical research studies showed that one out of six pediatric ALL patients survived for years after Total Therapy treatment. Says Dr. Pinkel, “In 1971, we published these results in the Journal of the American Medical Association, concluding that ‘a significant five-year-cure rate of childhood ALL is an attainable goal.’ But the fifth Total Therapy study, conducted in 1967-68, became the real winner, with half the children surviving in remission for now up to 40 years.”
The St. Jude website notes, “This was the first significant cure rate for generalized cancer and for primarily drug treatment of cancer.”
Recalls Dr. Evans, “Everybody who had been working so hard was suddenly seeing the possibility of success. You could feel it in the hallways and clinics and conference rooms, and that really reflected Don’s leadership and the fact that they had achieved something remarkable.
There was a real sense of urgency to get this done, and we still have that sense of urgency.”
Since then, continuing research has pushed the overall five-year ALL survival rate in pediatric patients over 80%. Thanks to clinical trials, “the great majority of our children can be cured of ALL,” says Martin Brecher, MD, current Chair of Pediatrics at RPCI.
“There was a whole cast of people who were very important” in boosting the cure rate for ALL, notes Dr. Evans. “Dr. Pinkel led the effort to put multiple drugs together and then combine them with radiation. It was getting all those pieces correct that pushed the cure rate to 50%. That changed the way everybody thought about treating disseminated cancer—and that it might be a winnable battle.
“I would submit that Dr. Pinkel informed the work of everybody who’s studying leukemia today.”
During his years in Memphis, Dr. Pinkel’s work with pediatric patients led him to notice serious protein-calorie undernutrition among babies and children in low-income, inner-city families. St. Jude conducted studies of the children and introduced a supplemental feeding program to correct the deficiencies, and that work contributed to the establishment of the federal government’s Special Supplemental Food Program for Women, Infants, and Children (WIC), which today serves more than eight million American babies, preschool children, and pregnant and lactating women. It has been called “the most cost-effective health program in the United States.”
Forty years later, Dr. Pinkel’s interest in child nutrition remains strong, so he was very happy when he learned recently that a particular young man, now in medical school, plans to pursue a career in international pediatric nutrition. For once upon a time, when the young man was a toddler with ALL, he was Dr. Pinkel’s patient.
“Most of the children surviving ALL are growing up well, healthy, and able to have successful lives,” says Dr. Pinkel. “They are doing well, and that’s the reward. A lot of children are doing well.”