A Life in Hematology

I assumed my duties as a fourth-year Harvard medical student on the Internal Medicine wards of the then Peter Bent Brigham Hospital in the fall of 1954 and almost immediately met the late E. Donnall Thomas, a recent chief resident and the acting hematologist. He talked to me about his hopes to create a safe and effective approach to bone marrow transplantation. I knew in an instant that I wanted to be a doctor like him. (Soon thereafter he moved to Cooperstown, NY, where he could carry out the canine studies that began his illustrious career.)

A year later, I became an intern on that service and struggled with my career options. Should I continue on the path that I thought I would follow – to be a subspecialty internist with an interest in liver disease, or should I establish a group practice in a poor area of Cambridge, MA, as I thought I would when I was a Harvard undergraduate? The Korean conflict settled the issue. I was invited to join the U.S. Public Health Service in the nascent clinical research program at the National Cancer Institute (NCI), which was led by the late Gordon Zubrod, a thorough gentleman. Alternatively, I could go to Korea in the Army. With a lovely wife and two children and another on the way, I wisely chose the former and was immediately ordered into experimental hematology by my appointed supervisor, then Captain (four stripes) the late Nathaniel I. Berlin. I had only two stripes on my sleeve, so hematology was my “choice.” I shared a lab with my Harvard classmates, Sherman Weissman and Tom Waldman. The late Dan Nathans was next door. George Brecher and Fred Stohlman were there to teach me. It was a remarkable environment, and I have been intensely loyal to the National Institutes of Health ever since.

Three years later, in 1959, I completed my senior residency in medicine at the Brigham and launched into a career in adult hematology under the watchful eye of the late Frank H. Gardner, a superb clinician. I decided to investigate thalassemia and the congenital hemolytic anemias because the patients fascinated me. I wanted to understand the pathophysiology of those diseases, and my work at NCI had given me some decent tools with which to explore the disorders. That work led me to establish many international friends, the most exciting of whom was and remains David Weatherall. David was knighted for his fine work, but has yet to introduce me to the Queen – a failing that he refuses to acknowledge.

In those years I labored in the Brigham lab with some wonderful colleagues like Chester Alper, Phin Cohen, Sergio Piomelli, Tom Gabuzda, Y.W. Kan, and Stanley Yachnin. All of us wanted to be clinical investigators examining patients and learning lessons about disease in the laboratory. Our goal was to be elected to membership in the American Society of Clinical Investigation. While working at the Brigham, I was greatly assisted by the late William Castle and his incredibly strong group at the then Thorndike Memorial Laboratory of the Harvard Service at the Boston City Hospital. The Thorndike was clearly the apex of hematology at Harvard and was one of the leading experimental hematology laboratories in the world. I learned something about myself in those years. I realized how much I needed to admire the leader of the unit to which I was assigned. Castle was the type of leader that I needed in my life. His advice, probity, and wisdom about patient-oriented research made my daily life in the lab and the clinic seem important. I came to realize then that I would always need to build my research around my patients; I was motivated by a desire to understand the physiologic and chemical bases of their illnesses and to try to define better approaches to diagnosis and treatment. I was less interested in biology for its own sake.

In the early to mid 1960s, I met the late Frank Oski, a developing pediatric hematologist at Boston Children’s Hospital (Children’s), who introduced me to one fascinating patient after another. Later we combined our efforts to initiate our textbook titled The Hematology of Infancy and Childhood. That book is now entering its eighth edition under the leadership of Stuart Orkin. My efforts with Frank Oski made me realize that the future of hematology surely laid in genetics and that pediatrics was indeed “genetics on the hoof.” Then suddenly in 1966, the late Charles A. Janeway came into my life. He was the chief of the Department of Medicine at Children’s and was searching for a successor to the late Louis K. Diamond who was retiring from his position as chief of hematology at Children’s. I deeply admired Janeway who had many of the characteristics of William Castle. I took that job because I knew that pediatrics had the patients who would fascinate me and advance my career, and I wanted to report to Janeway. In those days, there were far fewer rules. I had my boards in Internal Medicine, and after a few years I took the quiz and the oral exam and became board certified in Pediatrics. In fact, I served as chair of Janeway’s department at Children’s from 1985 to 1995. I never took hematology boards because I didn’t believe in them and still don’t. I firmly hold that a hematologist is someone who gains the approval of William Castle, Louis Diamond, Maxwell Wintrobe, or Carl Moore and their ilk. I suppose that view is now unacceptable. Despite my subspecialty board deficiency, I ran the Hematology/Oncology Division for 20 years and served as president of Dana-Farber Cancer Institute from 1995 to 2000. No one cared about the subspecialty boards; neither do I.

I have been at Children’s and then its close collaborating institution, Dana-Farber, since 1966. I first focused on the development of a pediatric hematology training program at Children’s and then a joint pediatric hematology and oncology training program at Children’s and Dana-Farber that was greatly enhanced by the support of my chiefs, the late Emil Frei and the late Baruj Benacerraf. I learned a very important lesson in those years: A physician–scientist must avoid dependence on any single technology. He must instead learn new technologies that will provide modern answers to new questions. To solve that need for continued scientific education, I crossed the Charles River to MIT on several occasions and joined Harvey Lodish, David Baltimore, and David Housman. I brought their approaches back to Children’s and Dana-Farber and applied them. With the added strength of MIT, I’ve trained (or did not interfere) with some of the best hematologists in the world. Many were internists like Bernie Forget, Y.W. Kan, Ed Benz, and Arthur Nienhuis. Frank Bunn had a lab in our division for some years. Others were pediatricians like David Williams, Sam Lux, Susan Shurin, Nancy Andrews, and Stuart Orkin. Now I have academic grandchildren like Len Zon, Charley Roberts, Mary Dinauer, and Vijay Sankaran – all whom have been trained by Stuart Orkin.

To my great pleasure, my present leaders are my own trainees – Ed Benz, David Williams, and Stuart Orkin. They have created a marvelous academic life for me. Now, with the support of the National Heart, Lung, and Blood Institute, I am investigating a new treatment approach to crisis in sickle cell anemia in concert with eight other institutions. At the age of 84, I am still rounding on in patients and attending clinics in hematology (admittedly in the company of very smart fellows who always know the right doses). I am still teaching hematology to medical students and even traveling to other centers to join in discussions of the incredible progress that I have seen. And I never miss the ASH annual meeting. We continue to have our Saturday night Vampire Dinner where the Children’s /Dana-Farber pediatric hematology/oncology trainees return to tell each other (and me) stories about “the old days.”

Yes, I was ordered into hematology. I don’t like orders very much, but that one was the best command I’ve ever received. I’ve been the recipient of some wonderfully exciting awards like the ASH Wallace H. Coulter Award (Read more about Dr. Nathan receiving the Wallace H. Coulter Award for Lifetime Achievement in 2011) and an honorary degree from Harvard. But the greatest honor has been the privilege of working with those bright young people and seeing their careers flourish. That has truly been the greatest academicjoy of all.

But my most profound happiness has come from my family. All these years, my wife Jean has stood by me and tolerated my love of academic hematology. In addition to our three children (one a musician, another an educator, and the third an attorney), we have been blessed with two marvelous sons-in-law and six exciting grandchildren. One of the grandchildren is a superb pediatric nurse at Children’s, another is going to medical school, and the four others include two musicians, a budding historian, and a college junior. Two of the six are married. Our meeting place is Nantucket in the summer where we sail, swim, and enjoy each other. Jean and I have been going to Nantucket in the summer since we were children. We met there more than 75 years ago. It’s been a glorious life together (at least for me!). I thank her deeply for making it all possible, and I particularly thank William B. Castle and Charles A. Janeway for setting a standard that I have tried to meet.

Stuart Orkin, MD

David G. Nathan Professor of Pediatrics, Harvard Medical School; Investigator, Howard Hughes Medical Institute; Chair, Department of Pediatric Oncology, Dana-Farber Cancer Institute

I have known David Nathan for more than 35 years and been proud to serve as the first incumbent of the David G. Nathan Professorship at Harvard Medical School. Each of us who has trained or worked with David Nathan has special reminiscences of his prowess as a clinician, clinician investigator, leader, and builder of academic institutions. Though an internist trained in adult hematology, he developed an extraordinary combined pediatric hematology and oncology program between Children’s and Dana-Farber and led the Department of Medicine (Pediatrics) at Children’s for a decade. During his tenure as department chair at Children’s, he garnered Howard Hughes Medical Institute support for the hospital, paving the way for its remarkable research presence over the past three decades. When called to serve as president at Dana-Farber at a challenging time in its history, he stabilized the institution and expanded both its research and clinical activities to better position it as a premier academic cancer center.

Despite these professional accomplishments, or perhaps in light of them, I most admire David’s humanism and humanity. Humanism places concern for human interests, values, and dignity at the center of care of the sick. Fueling David’s enthusiasm and passion in all aspects of academic medicine is his unwavering commitment to improving the lives of patients with potentially devastating illnesses. For him, a palpable connection between the laboratory and disease is what captures his attention and imagination and gives hope for improved therapy. David’s humanity is reflected in his loyalty and fairness in his interactions with trainees, colleagues, and patients. He embodied a steadfast mentor long before the practice of mentoring became a recognized academic exercise. For David, the person is always the focus.

As he nears his 85th birthday, we all marvel at his enthusiasm and engagement in all aspects of life. I can barely think of David, however, without also thinking of his wife Jean. Theirs is a remarkable love story. While choosing to remain in the background in David’s professional endeavors, Jean has given David her total support and made his family life a source of inestimable pleasure. We should all thank Jean for generously sharing David with us in the world of hematology.