Early Research of David G. Nathan, MD, Ushered in the Field of Pediatric Hematology


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David G. Nathan, MD

If I am going to leave you with any thought that sums up my life, it is that life in academic medicine is about family. My trainees are my second family, and watching their success is probably the thing that gives me the greatest happiness.

—David G. Nathan, MD

When David G. Nathan, MD, was admitted to Harvard University in 1947, he had every intention of becoming an English professor. It was only his lack of writing talent that dissuaded him from a life in the classroom and propelled him into a medical career that has spanned more than 5 decades and has led to the establishment of pediatric hematology/oncology as a new field of research and clinical care.

“I was very interested in writing and literature in college, and I had the whole uniform to become an English professor. I had the jacket with the leather elbow patches, the book bag, and the pipe. The only thing lacking was talent, and by the end of my sophomore year, I decided to major in medicine,” laughed Dr. Nathan, although, he admits, the seeds of a career in medicine were planted long before.

Born on May 25, 1929, in Boston, Dr. Nathan credits both his grandfather, Jacob Nathan, and his father, Geoffrey Nathan, with influencing his career choice, although for opposite reasons. “My grandfather had nothing but contempt for doctors because he said they didn’t do anything but sell people witchcraft,” said Dr. Nathan. “My father studied chemistry at Harvard University and went to work for my grandfather’s company, Roxbury Chemical Works, and then applied to Harvard Medical School and was accepted, but my grandfather wouldn’t allow him to study medicine. It was a missed opportunity for my father, but then I got to fulfill his dream.”

Decoding the Mystery of Disease

Although Dr. Nathan had planned to open a group medical practice in Cambridge after completing his medical studies at Harvard Medical School, an event during his second year there changed the trajectory of his career and led him to study the production of red blood cells and the treatment of children with leukemia and other blood diseases, especially thalassemia and sickle cell anemia.

“While making ward rounds with a resident at Boston City Hospital, I saw a patient in a coma and asked what was wrong with him. The resident said he didn’t know, but that the patient went into a coma every day after lunch,” said Dr. Nathan. “Although there was a theory that the problem was disordered ammonia metabolism, the doctors didn’t know for sure what was wrong with the patient, and that is what turned me into a physician/scientist. That incident was a turning point for me because I suddenly realized that what fascinates me is: (1) determining what’s wrong, and (2) figuring out what I can do about it.”

After completing his residency in internal medicine at Peter Bent Brigham Hospital (now Brigham and Women’s Hospital) in 1955, Dr. Nathan became a Clinical Associate at the National Cancer Institute (NCI). It was at the NCI that Dr. Nathan decided that he would devote his medical career to the clinical care and research of blood disorders.

“I don’t know how I was selected for the position at the NCI, but once there I was ordered into hematology by my research mentor, Nathaniel I. Berlin, MD, and I had 2 years training in hematology/oncology, mainly in disorders of the red blood cells, but also in leukemia,” said Dr. Nathan. “What a way to select a career—to be ordered into it—and I loved it. Once I got into hematology I never turned back.”

Charting a New Career Course

The use of multiple chemotherapy agents in the treatment of childhood leukemia, including methotrexate and mercaptopurine, had been initiated a few years before Dr. Nathan arrived at the NCI. But the therapy’s success rate was so low, Dr. Nathan lost every patient he treated with the two-combination therapy. It wasn’t until the four-drug combination of vincristine, doxorubicin, methotrexate, and prednisone was introduced in the early 1960s that oncologists finally started realizing cures in acute lymphocytic leukemia and in advanced Hodgkin lymphoma.

By then, however, Dr. Nathan had returned to Peter Bent Brigham Hospital to complete his senior residency in medicine. His interest in red blood cell abnormalities led him out of the study of internal medicine and into a focus on pediatric hematology.

“At the time, Brigham was highly advanced in kidney disease and in kidney transplant, and I got involved in the study of the red cell production in the transplant patients and learned a lot about the source of erythropoietin,” said Dr. Nathan. During this time, Dr. Nathan was also exposed to patients with difficult anemias and later developed hydroxyurea, the first successful treatment for sickle cell anemia.

Over the next 3 decades, Dr. Nathan had other major successes in the treatment of inherited blood disorders, including demonstrating how the continuous administration of deferoxamine, an iron-chelating agent, prolongs cardiac disease-free survival in thalassemia patients; and utilizing fetoscopy procedures in the prenatal detection of sickle cell anemia and thalassemia, which have contributed to the reduction of these diseases worldwide.

As Dr. Nathan’s research of inherited blood disorders became more widely known, he began treating young patients sent to him from Boston Children’s Hospital. In 1966, he decided to change his specialty from internal medicine to pediatrics and became Chief of the Division of Hematology and Oncology at Boston Children’s Hospital and the Sidney Farber Cancer Center, now the Dana-Farber Cancer Institute.

“At the time, I wasn’t thinking very much about the cancer problem, and I went to Children’s Hospital with the agreement that I wouldn’t be responsible for patients with cancer,” said Dr. Nathan. “They were the province of Dr. Sidney Farber [then Physician-in-Chief at Dana-Farber Cancer Institute], and I was very glad of that because I had had such a rough experience curing children of cancer at the NCI, and I really didn’t want to go through that again.”

Weighing Risk vs Benefit

However, by then, the aggressive use of combination chemotherapy in the treatment of acute lymphocytic leukemia and Hodgkin lymphoma was achieving complete remissions in about 25% to 30% of children with these cancers—and up to 60% by the end of the decade.1 This trend convinced Dr. ­Nathan that even though the treatment toxicities, including chemotherapy-induced bleeding, were difficult for patients, they were worth the potential chance at a cure, which ignited a feud with Dr. Farber that lasted until his death in 1973.

“Dr. Farber wanted to continue treating these children with sequential single-agent chemotherapy because he was terrified of injuring a child with these combination drugs, and I could understand his feeling,” said Dr. Nathan. “But I also knew that we would never cure patients unless we got over our fear, and I had a very hard time arguing with him about treating our young patients and begging him to use combination therapy. He would not do it, and we did not part as friends. He was furious with me and never spoke with me again. He died before I could reconcile with him.”

Combining the Fields

Dr. Nathan found an ally in Emil “Tom” Frei III, MD, who had succeeded Dr. Farber as Physician-in-Chief at Dana-Farber Cancer Institute, and who had pioneered, along with Emil J ­Freireich, MD, the use of combination chemotherapy as a multipronged assault on childhood leukemia at the NCI. “The arrival of Dr. Frei changed everything, and we combined the two units of hematology and oncology, which I ran until 1985,” said Dr. Nathan.

Over the next decade, from 1985 to 1995, Dr. Nathan served as Physician-in-Chief of Boston Children’s Hospital and became President of Dana-Farber Cancer Institute in 1995, remaining in that position until 2000. During those 5 years, Dr. Nathan transformed the institution from an insular cancer center into a central hub of oncology care, uniting five academic medical centers and two Harvard schools, and the organization is now known as the Dana-Farber/Harvard Cancer Center.

In addition to his research and clinical accomplishments, Dr. Nathan is acclaimed for his contribution to the training of hundreds of hematologists—many of whom now hold leading positions in pediatrics, oncology, and internal medicine—and for fostering collaboration among colleagues.

“We are in the biology business, and biology is terribly complicated,” said Dr. Nathan. “My feeling is that if you have a very tough problem, you want to pull all the best minds together to solve it. Sidney Farber was a sort of solo genius; it was hard to work with him because he was into himself. But the problems today are just so complicated, there is no way to solve them unless you collaborate with the best minds you can find. We owe it to our patients to bring our best efforts to the problem of cancer.”

Lasting Legacy in Patient Care

Today, Dr. Nathan is President Emeritus of Dana-Farber Cancer Institute, Physician-in-Chief Emeritus of Boston Children’s Hospital, and Robert A. Stranahan Distinguished Professor of Pediatrics and Professor of Medicine at Harvard Medical School. He still maintains an office for clinical research and teaching at Dana-Farber, where he is continuing his research in the inflammatory component of sickle cell anemia.

He is the recipient of numerous awards, including Boston Children’s Hospital Lifetime Award, John ­Stearns Medal for Lifetime Achievement in Medicine of the New York Academy of Medicine, George M. Kober Medal of the Association of American Physicians, Howland Medal of the American Pediatric Society, Annual Award for Excellence in Clinical Research from the National Institutes of Health, The President’s National Medal of Science, and the Henry Stratton and Wallace H. Coulter Medals of the American Society of Hematology, among others.

Looking back on his long career, Dr. Nathan said he is a “lucky guy” and credits his wife of 64 years, Jean, and their three children, Deborah, Linda, and Geof, with helping him achieve professional success. He also credits his “other” children—the many medical students and fellows he has mentored over the past 50 years—with contributing to his personal sense of accomplishment and satisfaction.

“Over the years, I’ve trained scores of students, and they have gone on to mentor their trainees, and that is the great multiplier. Frankly, I think my success is the result of the work of all those trainees,” said Dr. Nathan. “If I am going to leave you with any thought that sums up my life, it is that life in academic medicine is about family. My trainees are my second family, and watching their success is probably the thing that gives me the greatest happiness.”  ■

Reference

1. DeVita VT, Chu E: A history of cancer chemotherapy. Cancer Res 68:8643-8653, 2008.

 



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